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Investigative Ophthalmology & Visual Science
Journal Prestige (SJR): 2.058  Citation Impact (citeScore): 3 Number of Followers: 36  Subscription journalISSN (Print) 0146-0404 Published by ARVO  [1 journal]
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- Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Mouse Corneal
Epithelial Cells-
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Abstract: Purpose Corneal epithelial homeostasis is maintained by coordinated gene expression across distinct cell populations, but the gene regulatory programs underlying this cellular diversity remain to be characterized. Here we applied single-cell multi-omics analysis to delineate the gene regulatory profile of mouse corneal epithelial cells under normal homeostasis. Methods Single cells isolated from the cornea epithelium (with marginal conjunctiva) of adult mice were subjected to scRNA-seq and scATAC-seq using the 10×Genomics platform. Cell types were clustered by the graph-based visualization method uniform manifold approximation and projection and unbiased computational informatics analysis. The scRNA-seq and scATAC-seq datasets were integrated following the integration pipeline described in ArchR and Seurat. Results We characterized diverse corneal epithelial cell types based on gene expression signatures and chromatin accessibility. We found that cell type–specific accessibility regions were mainly located at distal regions, suggesting essential roles of distal regulatory elements in determining corneal epithelial cell diversity. Trajectory analyses revealed a continuum of cell state transition and higher coordination between transcription factor (TF) motif accessibility and gene expression during corneal epithelial cell differentiation. By integrating transcriptomic and chromatin accessibility analysis, we identified cell type-specific and shared gene regulation programs. We also uncovered critical TFs driving corneal epithelial cell differentiation, such as nuclear factor I (NFI) family members, Rarg, Elf3. We found that nuclear factor-κB (NF-κB) family members were positive TFs in limbal cells and some superficial cells, but they were involved in regulating distinct biological processes. Conclusions Our study presents a comprehensive gene regulatory landscape of mouse cornea epithelial cells, and provides valuable foundations for future investigation of corneal epithelial homeostasis in the context of cornea pathologies and regenerative medicine.
PubDate: Tue, 21 Mar 2023 13:57:26 GMT
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- Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate
Age-Related Macular Degeneration-
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Abstract: Purpose Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics. Methods We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0. Results Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (−0.55-fold), and succinic acid (−1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment. Conclusions Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.
PubDate: Mon, 20 Mar 2023 14:10:04 GMT
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- Differences in Outflow Facility Between Angiographically Identified High-
Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine
Eyes-
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Abstract: Purpose To investigate differences in outflow facility between angiographically determined high- and low-flow segments of the conventional outflow pathway in porcine eyes. Methods Porcine anterior segments (n = 14) were mounted in a perfusion chamber and perfused using Dulbecco's phosphate buffered solution with glucose. Fluorescein angiography was performed to determine high- and low-flow regions of the conventional outflow pathways. The trabecular meshwork (TM) was occluded using cyanoacrylate glue, except for residual 5-mm TM areas that were either high or low flow at baseline, designating these eyes as “residual high-flow” or “residual low-flow” eyes. Subsequently, outflow was quantitatively reassessed and compared between residual high-flow and residual low-flow eyes followed by indocyanine green angiography. Results Fluorescein aqueous angiography demonstrated high-flow and low-flow regions. Baseline outflow facilities were 0.320 ± 0.08 and 0.328 ± 0.10 µL/min/mmHg (P = 0.676) in residual high-flow and residual low-flow eyes before TM occlusion, respectively. After partial trabecular meshwork occlusion, outflow facility decreased to 0.209 ± 0.07 µL/min/mmHg (−32.66% ± 19.53%) and 0.114 ± 0.08 µL/min/mmHg (−66.57% ± 23.08%) in residual high- and low-flow eyes (P = 0.035), respectively. There was a significant difference in the resulting IOP increase (P = 0.034). Conclusions Angiographically determined high- and low-flow regions in the conventional outflow pathways differ in their segmental outflow facility; thus, there is an uneven distribution of local outflow facility across different parts of the TM.
PubDate: Mon, 20 Mar 2023 14:10:04 GMT
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- Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of
Filaggrin-2 and Signs of Neovascularization-
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Abstract: Purpose Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach. Methods We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation. Results Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis. Conclusions We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.
PubDate: Fri, 17 Mar 2023 14:22:04 GMT
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- Reviewers
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PubDate: Wed, 15 Mar 2023 14:37:43 GMT
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- Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal
Epithelium Defects in an Experimental Dry Eye Model-
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Abstract: Purpose Dry eye disease (DED) is a multifactorial disease that is associated with inflammation. Excessive DNA is present in the tear fluid of patients with DED. Absent in melanoma 2 (AIM2) is a key DNA sensor. This study aimed to investigate the role of AIM2 in the pathogenesis of DED. Methods DED was induced by injection of scopolamine (SCOP). Aberrant DNA was detected by cell-free DNA (cfDNA) ELISA and immunostaining. Corneal epithelial defects were assessed by corneal fluorescein staining, zonula occludens-1 immunostaining and TUNEL. Tear production was analyzed by phenol red thread test. Lacrimal gland (LG) histology was evaluated by hematoxylin and eosin staining, and transmission electron microscopy examination. Macrophage infiltration in LG was detected by immunohistochemistry for the macrophage marker F4/80. Gene expression was analyzed by RT-qPCR. Protein production was examined by immunoblot analysis or ELISA. Results Aim2−/− mice displayed a normal structure and function of LG and cornea under normal conditions. In SCOP-induced DED, wild type (WT) mice showed increased cfDNA in tear fluid, and aberrant accumulations of dsDNA accompanied by increased AIM2 expression in the LG. In SCOP-induced DED, WT mice displayed damaged structures of LG, reduced tear production, and severe corneal epithelium defects, whereas Aim2−/− mice had a better preserved LG structure, less decreased tear production, and improved clinical signs of dry eye. Furthermore, genetic deletion of Aim2 suppressed the increased infiltration of macrophages and inhibited N-GSDMD and IL18 production in the LG of SCOP-induced DED. Conclusions Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED.
PubDate: Wed, 15 Mar 2023 14:37:43 GMT
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- The Genetic Confirmation and Clinical Characterization of LOXL3
-Associated MYP28: A Common Type of Recessive Extreme High Myopia-
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Abstract: Purpose In previous studies, biallelic LOXL3 variants have been shown to cause autosomal recessive Stickler syndrome in one Saudi Arabian family or autosomal recessive early-onset high myopia (eoHM, MYP28) in two Chinese families. The current study aims to elucidate the clinical and genetic features of LOXL3-associated MYP28 in seven new families and two previously published families. Methods LOXL3 variants were detected based on the exome sequencing data of 8389 unrelated probands with various ocular conditions. Biallelic variants were identified through multiple online bioinformatic tools, comparative analysis, and co-segregation analysis. The available clinical data were summarized. Results Biallelic LOXL3 variants were exclusively identified in nine of 1226 families with eoHM but in none of the 7163 families without eoHM (P = 2.97 × 10−8, Fisher's exact test), including seven new and two previously reported families. Seven pathogenic variants were detected, including one nonsense (c.1765C>T/p.Arg589*), three frameshift (c.39dupG/p.Leu14Alafs*21; c.544delC/p.Leu182Cysfs*3, c.594delG/p.Gln199Lysfs*35), and three missense (c.371G>A/p.Cys124Tyr; c.1051G>A/p.Gly351Arg; c.1669G>A/p.Glu557Lys) variants. Clinical data of nine patients from nine unrelated families revealed myopia at the first visit at about 5 years of age, showing slow progression with age. Visual acuity at the last visit ranged from 0.04 to 0.9 (median age at last visit = 5 years, range 3.5–15 years). High myopic fundus changes, observed in all nine patients, were classified as tessellated fundus (C1) in five patients and diffuse choroidal atrophy (C2) in four patients. Electroretinograms showed mildly reduced cone responses and normal rod responses. Except for high myopia, no other specific features were shared by these patients. Conclusions Biallelic LOXL3 variants exclusively presenting in nine unrelated patients with eoHM provide firm evidence implicating MYP28, with an estimated prevalence of 7.3 × 10−3 in eoHM and of about 7.3 × 10−5 in the general population for LOXL3-associated eoHM. So far, MYP28 represents a common type of autosomal recessive extreme eoHM, with a frequency comparable to LRPAP1-associated MYP23.
PubDate: Tue, 14 Mar 2023 14:09:16 GMT
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- Ferritin But Not Iron Increases in Retina Upon Systemic Iron Overload in
Diabetic and Iron-Dextran Injected Mice-
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Abstract: Purpose Iron overload causes oxidative damage in the retina, and it has been involved in the pathogeny of diabetic retinopathy, which is one of the leading causes of blindness in the adult population worldwide. However, how systemic iron enters the retina during diabetes and the role of blood retinal barrier (BRB) in this process remains unclear. Methods The db/db mouse, a well-known model of type 2 diabetes, and a model of systemic iron overload induced by iron dextran intraperitoneal injection, were used. Perls staining and mass spectrophotometry were used to study iron content. Western blot and immunohistochemistry of iron handling proteins were performed to study systemic and retinal iron metabolism. BRB function was assessed by analyzing vascular leakage in fundus angiographies, whole retinas, and retinal sections and by studying the status of tight junctions using transmission electron microscopy and Western blot analysis. Results Twenty-week-old db/db mice with systemic iron overload presented ferritin overexpression without iron increase in the retina and did not show any sign of BRB breakdown. These findings were also observed in iron dextran-injected mice. In those animals, after BRB breakdown induced by cryopexy, iron entered massively in the retina. Conclusions Our results suggested that BRB protects the retina from excessive iron entry in early stages of diabetic retinopathy. Furthermore, ferritin overexpression before iron increase may prepare the retina for a potential BRB breakdown and iron entry from the systemic circulation.
PubDate: Mon, 13 Mar 2023 12:18:06 GMT
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- Phenotypic Variability of Retinal Disease Among a Cohort of Patients With
Variants in the CLN Genes-
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Abstract: Purpose To describe the phenotype of CLN-associated retinal dystrophy in a subset of patients at the Columbia University Medical Center, United States, and the Hospital das Clínicas de Pernambuco, Brazil, in comparison to the published literature. Methods Eleven patients with confirmed biallelic variants in the CLN genes were evaluated via dilated fundus examination, clinical imaging, and full-field electroretinogram. A thorough literature search was conducted to determine previously published variants and associated phenotypes. Results Genetic testing confirmed the presence of variants in CLN3, CLN7/MFSD8, CLN8, and GRN/CLN11. Five novel variants were identified, and four novel phenotypes of previously published alleles were described. The phenotype differed among patients with variants in the same gene and sometimes among patients with the same allele. Conclusions Substantial phenotypic variability among variants in the CLN genes makes identification of genotype–phenotype or allele–phenotype correlations challenging. Further study is required to establish an extensive database for adequate patient counseling.
PubDate: Mon, 13 Mar 2023 12:18:06 GMT
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- Overactivation of Norepinephrine–β2-Adrenergic Receptor Axis Promotes
Corneal Neovascularization-
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Abstract: Purpose To investigate the role of the sympathetic nervous system in corneal neovascularization (CNV) and to identify the downstream pathway involved in this regulation. Methods Three types of CNV models were constructed with C57BL/6J mice, including the alkali burn model, suture model, and basic fibroblast growth factor (bFGF) corneal micropocket model. Subconjunctival injection of the sympathetic neurotransmitter norepinephrine (NE) was administered in these three models. Control mice received injections of water of the same volume. The corneal CNV was detected using slit-lamp microscopy and immunostaining with CD31, and the results were quantified by ImageJ. The expression of β2-adrenergic receptor (β2-AR) was stained with mouse corneas and human umbilical vein endothelial cells (HUVECs). Furthermore, the anti-CNV effects of β2-AR antagonist ICI-118,551 (ICI) were examined with HUVEC tube formation assay and with a bFGF micropocket model. Additionally, partial β2-AR knockdown mice (Adrb2+/−) were used to establish the bFGF micropocket model, and the corneal CNV size was quantified based on the slit-lamp images and vessel staining. Results Sympathetic nerves invaded the cornea in the suture CNV model. The NE receptor β2-AR was highly expressed in corneal epithelium and blood vessels. The addition of NE significantly promoted corneal angiogenesis, whereas ICI effectively inhibited CNV invasion and HUVEC tube formation. Adrb2 knockdown significantly reduced the cornea area occupied by CNV. Conclusions Our study found that sympathetic nerves grow into the cornea in conjunction with newly formed vessels. The addition of the sympathetic neurotransmitter NE and activation of its downstream receptor β2-AR promoted CNV. Targeting β2-AR could potentially be used as an anti-CNV strategy.
PubDate: Fri, 10 Mar 2023 13:23:06 GMT
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- Choroidal Microvasculature Dropout in the Absence of Parapapillary Atrophy
in POAG-
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Abstract: Purpose To describe the parapapillary choroidal microvasculature dropout (CMvD) in glaucomatous eyes without β-zone parapapillary atrophy (β-PPA) and compare its characteristics with that of CMvD with β-PPA. Methods Peripapillary choroidal microvasculature was evaluated on en face images obtained using optical coherence tomography angiography. CMvD was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Peripapillary and optic nerve head structures, including the presence of β-PPA, peripapillary choroidal thickness and lamina cribrosa curvature index were evaluated using the images obtained by enhanced depth-imaging optical coherence tomography. Results The study included 100 glaucomatous eyes with CMvD (25 without and 75 with β-PPA) and 97 eyes without CMvD (57 without and 40 with β-PPA). Regardless of the presence of β-PPA, eyes with CMvD tended to have a worse visual field at a given RNFL thickness than eyes without CMvD, with patients having eyes with CMvD having lower diastolic blood pressure and more frequent cold extremities than patients with eyes lacking CMvD. Peripapillary choroidal thickness was significantly smaller in eyes with than without CMvD, but was not affected by the presence of β-PPA. β-PPA without CMvD was not associated with vascular variables. Conclusions CMvD were found in the absence of β-PPA in glaucomatous eyes. CMvDs had similar characteristics in the presence and absence of β-PPA. Clinical and optic nerve head structural characteristics potentially relevant to compromised optic nerve head perfusion were dependent on the presence of CMvD, rather than the presence of β-PPA.
PubDate: Fri, 10 Mar 2023 13:23:06 GMT
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- Tissue-Specific Sex Difference in Mouse Eye and Brain Metabolome Under Fed
and Fasted States-
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Abstract: Purpose Visual physiology and various ocular diseases demonstrate sexual dimorphisms; however, how sex influences metabolism in different eye tissues remains undetermined. This study aims to address common and tissue-specific sex differences in metabolism in the retina, RPE, lens, and brain under fed and fasted conditions. Methods After ad libitum fed or being deprived of food for 18 hours, mouse eye tissues (retina, RPE/choroid, and lens), brain, and plasma were harvested for targeted metabolomics. The data were analyzed with both partial least squares-discriminant analysis and volcano plot analysis. Results Among 133 metabolites that cover major metabolic pathways, we found 9 to 45 metabolites that are sex different in different tissues under the fed state and 6 to 18 metabolites under the fasted state. Among these sex-different metabolites, 33 were changed in 2 or more tissues, and 64 were tissue specific. Pantothenic acid, hypotaurine, and 4-hydroxyproline were the top commonly changed metabolites. The lens and the retina had the most tissue-specific, sex-different metabolites enriched in the metabolism of amino acid, nucleotide, lipids, and tricarboxylic acid cycle. The lens and the brain had more similar sex-different metabolites than other ocular tissues. The female RPE and female brain were more sensitive to fasting with more decreased metabolites in amino acid metabolism, tricarboxylic acid cycles, and glycolysis. The plasma had the fewest sex-different metabolites, with very few overlapping changes with tissues. Conclusions Sex has a strong influence on eye and brain metabolism in tissue-specific and metabolic state-specific manners. Our findings may implicate the sexual dimorphisms in eye physiology and susceptibility to ocular diseases.
PubDate: Thu, 09 Mar 2023 14:55:08 GMT
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- Missense Mutations in MAB21L1 : Causation of Novel Autosomal Dominant
Ocular BAMD Syndrome-
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Abstract: Purpose Biallelic MAB21L1 variants have been reported to cause autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG), whereas only five heterozygous pathogenic variants have been suspected to cause autosomal dominant (AD) microphthalmia and aniridia in eight families. This study aimed to report an AD ocular syndrome (blepharophimosis plus anterior segment and macular dysgenesis [BAMD]) syndrome based on clinical and genetic findings from patients with monoallelic MAB21L1 pathogenic variants in our cohort and reported cases. Methods Potential pathogenic variants in MAB21L1 were detected from a large in-house exome sequencing dataset. Ocular phenotypes of the patients with potential pathogenic variants in MAB21L1 were summarized, and the genotype-phenotype correlation was analyzed through a comprehensive literature review. Results Three heterozygous missense variants in MAB21L1, predicted to be damaging, were detected in 5 unrelated families, including c.152G>T in 2, c.152G>A in 2, and c.155T>G in one. All were absent from gnomAD. The variants were de novo in two families, transmitted from affected parents to offspring in two families, and with an unknown origin in the other family, demonstrating strong evidence of AD inheritance. All patients revealed similar BAMD phenotypes, including blepharophimosis, anterior segment dysgenesis, and macular dysgenesis. Genotype-phenotype analysis suggested that patients with monoallelic MAB21L1 missense variants had only ocular anomalies (BAMD), whereas patients with biallelic variants presented both ocular and extraocular symptoms. Conclusions Heterozygous pathogenic variants in MAB21L1 account for a new AD BAMD syndrome, which is completely different from COFG caused by homozygous variants in MAB21L1. Nucleotide c.152 is likely a mutation hot spot, and the encoded residue of p.Arg51 might be critical for MAB21L1.
PubDate: Thu, 09 Mar 2023 14:55:08 GMT
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- SIRT1 Inhibits High Glucose–Induced TXNIP/NLRP3 Inflammasome
Activation and Cataract Formation-
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Abstract: Purpose To determine whether SIRT1 regulates high glucose (HG)–induced inflammation and cataract formation through modulating TXNIP/NLRP3 inflammasome activation in human lens epithelial cells (HLECs) and rat lenses. Methods HG stress from 25 to 150 mM was imposed on HLECs, with treatments using small interfering RNAs (siRNAs) targeting NLRP3, TXNIP, and SIRT1, as well as a lentiviral vector (LV) for SIRT1. Rat lenses were cultivated with HG media, with or without the addition of NLRP3 inhibitor MCC950 or SIRT1 agonist SRT1720. High mannitol groups were applied as the osmotic controls. Real-time PCR, Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of SIRT1, TXNIP, NLRP3, ASC, and IL-1β. Reactive oxygen species (ROS) generation, cell viability, and death were also assessed. Results HG stress induced a decline in SIRT1 expression and caused TXNIP/NLRP3 inflammasome activation in a concentration-dependent manner in HLECs, which was not observed in the high mannitol–treated groups. Knocking down NLRP3 or TXNIP inhibited NLRP3 inflammasome-induced IL-1β p17 secretion under HG stress. Transfections of si-SIRT1 and LV-SIRT1 exerted inverse effects on NLRP3 inflammasome activation, suggesting that SIRT1 acts as an upstream regulator of TXNIP/NLRP3 activity. HG stress induced lens opacity and cataract formation in cultivated rat lenses, which was prevented by MCC950 or SRT1720 treatment, with concomitant reductions in ROS production and TXNIP/NLRP3/IL-1β expression levels. Conclusions The TXNIP/NLRP3 inflammasome pathway promotes HG-induced inflammation and HLEC pyroptosis, which is negatively regulated by SIRT1. This suggests viable strategies for treating diabetic cataract.
PubDate: Tue, 07 Mar 2023 15:31:41 GMT
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- Spatial Resolution Evaluation Based on Experienced Visual Categories With
Sweep Evoked Periodic EEG Activity-
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Abstract: Purpose Visual function is typically evaluated in clinical settings with visual acuity (VA), a test requiring to behaviorally match or name optotypes such as tumbling E or Snellen letters. The ability to recognize these symbols has little in common with the automatic and rapid visual recognition of socially important stimuli in real life. Here we use sweep visual evoked potentials to assess spatial resolution objectively based on the recognition of human faces and written words. Methods To this end, we tested unfamiliar face individuation1 and visual word recognition2 in 15 normally sighted adult volunteers with a 68-electrode electroencephalogram system. Results Unlike previous measures of low-level visual function including VA, the most sensitive electrode was found at an electrode different from Oz in a majority of participants. Thresholds until which faces and words could be recognized were evaluated at the most sensitive electrode defined individually for each participant. Word recognition thresholds corresponded with the VA level expected from normally sighted participants, and even a VA significantly higher than expected from normally sighted individuals for a few participants. Conclusions Spatial resolution can be evaluated based on high-level stimuli encountered in day-to-day life, such as faces or written words with sweep visual evoked potentials.
PubDate: Tue, 07 Mar 2023 15:31:41 GMT
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- Correlation Between Retinal Vessel Diameters and Uveitis Activity
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Abstract: Purpose To assess retinal vein and artery diameters during active and inactive intraocular inflammation in eyes with uveitis. Methods Color fundus photographs and clinical data of eyes with uveitis collected during two visits (active disease [i.e., T0] and inactive stage [i.e., T1]) were reviewed. The images were semi-automatically analyzed to obtain the central retina vein equivalent (CRVE) and central retina artery equivalent (CRAE). Changes of CRVE and CRAE from T0 to T1 were calculated, and their possible correlation with clinical data, including age, gender, ethnicity, uveitis etiology, and visual acuity, were investigated. Results Eighty-nine eyes were enrolled in the study. Both CRVE and CRAE reduced from T0 to T1 (P < 0.0001 and P = 0.01, respectively), with active inflammation being able to influence the CRVE and CRAE (P < 0.0001 and P = 0.0004, respectively) after accounting for all other variables. The degree of venular (∆V) and arteriolar (∆A) dilation was influenced only by time (P = 0.03 and P = 0.04, respectively). Best-corrected visual acuity was influenced by time and ethnicity (P = 0.003 and P = 0.0006). Conclusions CRVE and CRAE are increased in eyes with active intraocular inflammation regardless of the type of uveitis, and they decrease when the inflammation wears off.
PubDate: Mon, 06 Mar 2023 15:00:34 GMT
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- T-Cell Repertoire Analysis in the Conjunctiva of Murine Dry Eye Model
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Abstract: Purpose Dry eye is closely related to the activation and proliferation of immune cells, especially T cells. However, the determination of the preferential T-cell clonotypes is technically challenging. This study aimed to investigate the characterization of T-cell receptor (TCR) repertoire in the conjunctiva during dry eye. Methods A desiccating stress animal model was established using C57/BL6 mice (8–10 weeks, female). After 7 days of stress stimulation, the slit-lamp image and Oregon–green–dextran staining were used to evaluate the ocular surface injury. Periodic acid–Schiff staining was used to measure the number of goblet cells. Flow cytometry was used to detect the activation and proliferation of T cells in the conjunctiva and cervical lymph nodes. Next-generation sequencing was used to detect the αβ TCR repertoire of the conjunctiva. Results The αβ TCR diversity increased significantly in the dry eye group, including the higher CDR3 amino acid length, marked gene usage on TCR V and J gene segments, extensive V(D)J recombination, and distinct CDR3 aa motifs. More important, several T-cell clonotypes were uniquely identified in dry eye. Furthermore, these perturbed rearrangements were reversed after glucocorticoid administration. Conclusions A comprehensive analysis of the αβ TCR repertoire in the conjunctiva of the dry eye mouse model was performed. Data in this study contributed significantly to the research on dry eye pathogenesis by demonstrating the TCR gene distribution and disease-specific TCR signatures. This study further provided some potential predictive T-cell biomarkers for future studies.
PubDate: Mon, 06 Mar 2023 15:00:34 GMT
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- Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the
Bimatoprost Implant-
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Abstract: Purpose The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues. Methods MMP gene expression by human trabecular meshwork (TM), scleral fibroblast (SF), and ciliary muscle (CM) cells exposed to 10 to 1000 µM bimatoprost or 0.1 to 10 µM BFA (intraocular concentrations after intracameral bimatoprost implant and topical bimatoprost dosing, respectively) was measured by polymerase chain reaction array. Results Bimatoprost dose-dependently upregulated MMP1 and MMP14 mRNA in all cell types and MMP10 and MMP11 mRNA in TM and CM cells; in TM cells from normal eyes, mean MMP1 mRNA levels were 62.9-fold control levels at 1000 µM bimatoprost. BFA upregulated MMP1 mRNA only in TM and SF cells, to two- to three-fold control levels. The largest changes in extracellular matrix (ECM)-related gene expression by TM cells derived from normal (n = 6) or primary open-angle glaucoma (n = 3) eyes occurred with 1000 µM bimatoprost (statistically significant, ≥50% change for 9–11 of 84 genes on the array, versus 1 gene with 10 µM BFA). Conclusions Bimatoprost and BFA had differential effects on MMP/ECM gene expression. Dramatic upregulation in MMP1 and downregulation of fibronectin, which occurred only with bimatoprost at high concentrations observed in bimatoprost implant–treated eyes, may promote sustained outflow tissue remodeling and long-term intraocular pressure reduction beyond the duration of intraocular drug bioavailability. Variability in bimatoprost-stimulated MMP upregulation among cell strains from different donors may help explain differential long-term responses of patients to bimatoprost implant.
PubDate: Mon, 06 Mar 2023 15:00:34 GMT
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- The Role of C-X-C Chemokines in Staphylococcus aureus Endophthalmitis
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Abstract: Purpose To test the hypothesis that the C-X-C chemokines CXCL1, CXCL2, and CXCL10 contribute to inflammation during Staphylococcus aureus endophthalmitis. Methods S. aureus endophthalmitis was induced by intravitreal injection of 5000 colony forming units of S. aureus into the eyes of C57BL/6J, CXCL1−/−, CXCL2−/−, or CXCL10−/− mice. At 12, 24, and 36 hours postinfection, bacterial counts, intraocular inflammation, and retinal function were assessed. Based on these results, the effectiveness of intravitreal administration of anti-CXCL1 in reducing inflammation and improving retinal function was evaluated in S. aureus–infected C57BL/6J mice. Results We observed significant attenuation of inflammation and improvement in retinal function in CXCL1−/− mice relative to C57BL/6J at 12 hours but not at 24 or 36 hours postinfection with S. aureus. Co-administration of anti-CXCL1 antibodies with S. aureus, however, did not improve retinal function or reduce inflammation at 12 hours postinfection. In CXCL2−/− and CXCL10−/− mice, retinal function and intraocular inflammation were not significantly different from those of C57BL/6J mice at 12 and 24 hours postinfection. At 12, 24, or 36 hours, an absence of CXCL1, CXCL2, or CXCL10 did not alter intraocular S. aureus concentrations. Conclusions CXCL1 appears to contribute to the early host innate response to S. aureus endophthalmitis, but treatment with anti-CXCL1 did not effectively limit inflammation in this infection. CXCL2 and CXCL10 did not seem to play an integral role in inflammation during the early stages of S. aureus endophthalmitis.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Physical Activity Is Associated With Macular Thickness: A Multi-Cohort
Observational Study-
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Abstract: Purpose To assess the association between physical activity and spectral-domain optical coherence tomography (SD-OCT)–measured rates of macular thinning in an adult population with primary open-angle glaucoma. Methods The correlation between accelerometer-measured physical activity and rates of macular ganglion cell–inner plexiform layer (GCIPL) thinning was measured in 735 eyes from 388 participants of the Progression Risk of Glaucoma: RElevant SNPs with Significant Association (PROGRESSA) study. The association between accelerometer-measured physical activity and cross-sectional SD-OCT macular thickness was then assessed in 8862 eyes from 6152 participants available for analysis in the UK Biobank who had SD-OCT, ophthalmic, comorbidity, and demographic data. Results Greater physical activity was associated with slower rates of macular GCIPL thinning in the PROGRESSA study (beta = 0.07 µm/y/SD; 95% confidence interval [CI], 0.03–0.13; P = 0.003) after adjustment for ophthalmic, demographic and systemic predictors of macular thinning. This association persisted in subanalyses of participants characterized as glaucoma suspects (beta = 0.09 µm/y/SD; 95% CI, 0.03–0.15; P = 0.005). Participants in the upper tertile (greater than 10,524 steps/d) exhibited a 0.22-µm/y slower rate of macular GCIPL thinning than participants in the lower tertile (fewer than 6925 steps/d): −0.40 ± 0.46 µm/y versus −0.62 ± 0.55 µm/y (P = 0.003). Both time spent doing moderate/vigorous activity and mean daily active calories were positively correlated with rate of macular GCIPL thinning (moderate/vigorous activity: beta = 0.06 µm/y/SD; 95% CI, 0.01–0.105; P = 0.018; active calories: beta = 0.06 µm/y/SD; 95% CI, 0.006–0.114; P = 0.032). Analysis among 8862 eyes from the UK Biobank revealed a positive association between physical activity and cross-sectional total macular thickness (beta = 0.8 µm/SD; 95% CI, 0.47–1.14; P < 0.001). Conclusions These results highlight the potential neuroprotective benefits of exercise on the human retina.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Multiple Bioenergy-Linked OCT Biomarkers Suggest Greater-Than-Normal Rod
Mitochondria Activity Early in Experimental Alzheimer's Disease-
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Abstract: Purpose In Alzheimer's disease, central brain neurons show evidence for early hyperactivity. It is unclear if this occurs in the retina, another disease target. Here, we tested for imaging biomarker manifestation of prodromal hyperactivity in rod mitochondria in vivo in experimental Alzheimer's disease. Methods Light- and dark-adapted 4-month-old 5xFAD and wild-type (WT) mice, both on a C57BL/6J background, were studied with optical coherence tomography (OCT). We measured the reflectivity profile shape of the inner segment ellipsoid zone (EZ) as a proxy for mitochondria distribution. Two additional indices responsive to mitochondria activity were also measured: the thickness of the external limiting membrane–retinal pigment epithelium (ELM-RPE) region and the signal magnitude of a hyporeflective band (HB) between photoreceptor tips and apical RPE. Retinal laminar thickness and visual performance were evaluated. Results In response to low energy demand (light), WT mice showed the expected elongation in EZ reflectivity profile shape, relatively thicker ELM-RPE, and greater HB signal. Under high energy demand (dark), the EZ reflectivity profile shape was rounder, the ELM-RPE was thinner, and the HB was reduced. These OCT biomarker patterns for light-adapted 5xFAD mice did not match those of light-adapted WT mice but rather that of dark-adapted WT mice. Dark-adapted 5xFAD and WT mice showed the same biomarker pattern. The 5xFAD mice exhibited modest nuclear layer thinning and lower-than-normal contrast sensitivity. Conclusions Results from three OCT bioenergy biomarkers raise the novel possibility of early rod hyperactivity in vivo in a common Alzheimer's disease model.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Time-Course Transcriptomic Analysis Reveals the Crucial Roles of
PANoptosis in Fungal Keratitis-
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Abstract: Purpose Fungal keratitis (FK) is a serious corneal infection with high morbidity. Host immune responses function as a double-edged sword by eradicating fungal pathogens while also causing corneal damage, dictating the severity, progression, and outcome of FK. However, the underlying immunopathogenesis remains elusive. Methods Time-course transcriptome was performed to illustrate the dynamic immune landscape in a mouse model of FK. Integrated bioinformatic analyses included identification of differentially expressed genes, time series clustering, Gene Ontology enrichment, and inference of infiltrating immune cells. Gene expression was verified by quantitative polymerase chain reaction (qPCR), Western blot, or immunohistochemistry. Results FK mice exhibited dynamic immune responses with concerted trends with clinical score, transcriptional alteration, and immune cell infiltration score peaking at 3 days post infection (dpi). Disrupted substrate metabolism, broad immune activation, and corneal wound healing occurred sequentially in early, middle, and late stages of FK. Meanwhile, dynamics of infiltrating innate and adaptive immune cells displayed distinct characteristics. Proportions of dendritic cells showed overall decreasing trend with fungal infection, whereas that of macrophages, monocytes, and neutrophils rose sharply in early stage and then gradually decreased as inflammation resolved. Activation of adaptive immune cells was also observed in late stage of infection. Furthermore, shared immune responses and activation of AIM2-, pyrin-, and ZBP1-mediated PANoptosis were revealed across different time points. Conclusions Our study profiles the dynamic immune landscape and highlights the crucial roles of PANoptosis in FK pathogenesis. These findings provide novel insights into host responses to fungi and contribute to the development of PANoptosis-targeted therapeutics for patients with FK.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Causal Relationships Between Glycemic Traits and Myopia
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Abstract: Purpose Little is known about whether sugar intake is a risk factor for myopia, and the influence of glycemic control remains unclear, with inconsistent results reported. This study aimed to clarify this uncertainty by evaluating the link between multiple glycemic traits and myopia. Methods We employed a two-sample Mendelian randomization (MR) design using summary statistics from independent genome-wide association studies. A total of six glycemic traits, including adiponectin, body mass index, fasting blood glucose, fasting insulin, hemoglobin A1c (HbA1c), and proinsulin levels, were used as exposures, and myopia was used as the outcome. The inverse-variance-weighted (IVW) method was the main applied analytic tool and was complemented with comprehensive sensitivity analyses. Results Out of the six glycemic traits studied, we found that adiponectin was significantly associated with myopia. The genetically predicted level of adiponectin was consistently negatively associated with myopia incidence: IVW (odds ratio [OR] = 0.990; P = 2.66 × 10−3), MR Egger (OR = 0.983; P = 3.47 × 10−3), weighted median method (OR = 0.989; P = 0.01), and weighted mode method (OR = 0.987; P = 0.01). Evidence from all sensitivity analyses further supported these associations. In addition, a higher HbA1c level was associated with a greater risk of myopia: IVW (OR = 1.022; P = 3.06 × 10−5). Conclusions Genetic evidence shows that low adiponectin levels and high HbA1c are associated with an increased risk of myopia. Given that physical activity and sugar intake are controllable variables in blood glycemia treatment, these findings provide new insights into potential strategies to delay myopia onset.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Single-Cell Characterization of the Frizzled 5 ( Fz5 ) Mutant Mouse and
Human Persistent Fetal Vasculature (PFV)-
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Abstract: Purpose Persistent fetal vasculature (PFV) is a pathological condition accounting for 4.8% of children's blindness in the United States. However, the PFV cell composition and pathogenetic mechanisms are poorly understood. This study aims to characterize PFV cell composition and associated molecular features and attempts to lay a foundation for further understanding the disease. Methods Immunohistochemistry was conducted to characterize cell types at the tissue level. Single-cell RNA sequencing (sc-RNAseq) was performed on the vitreous cells derived from normal and Fz5 mutant mice at two early postnatal ages and human PFV samples. Bioinformatic tools were used to cluster cells and analyze their molecular features and functions. Results The findings of this study are as follows: (1) a total of 10 defined and one undefined cell types were characterized in both the hyaloid vessel system and PFV by sc-RNAseq and immunohistochemistry; (2) neural crest-derived melanocytes, astrocytes, and fibroblasts were specifically retained in the mutant PFV; (3) Fz5 mutants were found to possess more vitreous cells at early postnatal age 3 but returned to similar levels as the wild type at postnatal age 6; (4) altered phagocytic and proliferation environments and cell-cell interactions were detected in the mutant vitreous; (5) the human PFV samples shared fibroblast, endothelial and macrophage cell types with the mouse, but having distinct immune cells including T cells, NK cells and Neutrophils; and last, (6) some neural crest features were also shared between certain mouse and human vitreous cell types. Conclusions We characterized PFV cell composition and associated molecular features in the Fz5 mutant mice and two human PFV samples. The excessively migrated vitreous cells, intrinsic molecular properties of these cells, phagocytic environment, and cell-cell interactions may together contribute to PFV pathogenesis. Human PFV shares certain cell types and molecular features with the mouse.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Celastrol Alleviates Corneal Stromal Fibrosis by Inhibiting
TGF-β1/Smad2/3-YAP/TAZ Signaling After Descemet Stripping Endothelial
Keratoplasty-
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Abstract: Purpose The purpose of this study was to investigate the effect of celastrol (CEL) on corneal stromal fibrosis after Descemet stripping endothelial keratoplasty (DSEK) and its associated mechanism. Methods Rabbit corneal fibroblasts (RCFs) were isolated, cultured, and identified. A CEL-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration. CCK-8 and scratch assays were performed to evaluate cytotoxicity and the effects of CEL on the migration of RCFs. The RCFs were activated by TGF-β1 with or without CEL treatment, and then the protein expression levels of TGFβRII, Smad2/3, YAP, TAZ, TEAD1, α-SMA, TGF-β1, FN, and COLI were assessed by immunofluorescence or Western blotting (WB). An in vivo DSEK model was established in New Zealand White rabbits. The corneas were stained using H&E, YAP, TAZ, TGF-β1, Smad2/3, TGFβRII, Masson, and COLI. H&E staining of the eyeball was performed to assess the tissue toxicity of CEL at 8 weeks after DSEK. Results In vitro CEL treatment inhibited the proliferation and migration of RCFs induced by TGF-β1. Immunofluorescence and WB showed that CEL significantly inhibited the protein expression of TGF-β1, Smad2/3, YAP, TAZ, TEAD1, α-SMA, TGF-βRII, FN, and COL1 induced by TGF-β1 in RCFs. In the rabbit DSEK model, CEL significantly reduced the levels of YAP, TAZ, TGF-β1, Smad2/3, TGFβRII, and collagen. No obvious tissue toxicity was observed in the CPNM group. Conclusions CEL effectively inhibited corneal stromal fibrosis after DSEK. The TGF-β1/Smad2/3-YAP/TAZ pathway may be involved in the mechanism by which CEL alleviates corneal fibrosis. The CPNM is a safe and effective treatment strategy for corneal stromal fibrosis after DSEK.
PubDate: Fri, 03 Mar 2023 14:51:43 GMT
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- Clinicopathologic Findings in Three Siblings With Geographic Atrophy
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Abstract: Purpose Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Clinical imaging and histopathologic studies are crucial to understanding disease pathology. This study combined clinical observations of three brothers with geographic atrophy (GA), followed for 20 years, with histopathologic analysis. Methods For two of the three brothers, clinical images were taken in 2016, 2 years prior to death. Immunohistochemistry, on both flat-mounts and cross sections, histology, and transmission electron microscopy were used to compare the choroid and retina in GA eyes to those of age-matched controls. Results Ulex europaeus agglutinin (UEA) lectin staining of the choroid demonstrated a significant reduction in the percent vascular area and vessel diameter. In one donor, histopathologic analysis demonstrated two separate areas with choroidal neovascularization (CNV). Reevaluation of swept-source optical coherence tomography angiography (SS-OCTA) images revealed CNV in two of the brothers. UEA lectin also revealed a significant reduction in retinal vasculature in the atrophic area. A subretinal glial membrane, composed of processes positive for glial fibrillary acidic protein and/or vimentin, occupied areas identical to those of retinal pigment epithelium (RPE) and choroidal atrophy in all three AMD donors. SS-OCTA also demonstrated presumed calcific drusen in the two donors imaged in 2016. Immunohistochemical analysis and alizarin red S staining verified calcium within drusen, which was ensheathed by glial processes. Conclusions This study demonstrates the importance of clinicohistopathologic correlation studies. It emphasizes the need to better understand how the symbiotic relationship between choriocapillaris and RPE, glial response, and calcified drusen impact GA progression.
PubDate: Thu, 02 Mar 2023 14:39:24 GMT
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- 24-Hour Monitoring of Intraocular Pressure Fluctuations Using a Contact
Lens Sensor: Diagnostic Performance for Glaucoma Progression-
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Abstract: Purpose The purpose of this study was to compare 24-hour intraocular pressure (IOP) related fluctuations monitoring between 2 groups of visual field progression rates in patients with open angle glaucoma (OAG). Methods Cross-sectional study performed at Bordeaux University Hospital. Twenty-four-hour monitoring was performed using a contact lens sensor (CLS; Triggerfish; SENSIMED, Etagnières, Switzerland). Progression rate was calculated using a linear regression of the mean deviation (MD) parameter of the visual field test (Octopus; HAAG-STREIT, Switzerland). Patients were allocated into two groups: group 1 with an MD progression rate <−0.5 dB/year and group 2 with an MD progression rate ≥−0.5 dB/year. An automatic signal-processing program was developed and a frequency filtering of the monitoring by wavelet transform analysis was used to compare the output signal between the two groups. A multivariate classifier was performed for prediction of the faster progression group. Results Fifty-four eyes of 54 patients were included. The mean progression rate was −1.09 ± 0.60 dB/year in group 1 (n = 22) and −0.12 ± 0.13 dB/year in group 2 (n = 32). Twenty-four-hour magnitude and absolute area under the monitoring curve were significantly higher in group 1 than in group 2 (group 1: 343.1 ± 62.3 millivolts [mVs] and 8.28 ± 2.10 mVs, respectively, group 2: 274.0 ± 75.0 mV and 6.82 ± 2.70 mVs respectively, P < 0.05). Magnitude and area under the wavelet curve for short frequency periods ranging from 60 to 220 minutes were also significantly higher in group 1 (P < 0.05). Conclusions The 24-hour IOP related fluctuations characteristics, as assessed by a CLS, may act as a risk factor for progression in OAG. In association with other predictive factors of glaucoma progression, the CLS may help adjust treatment strategy earlier.
PubDate: Thu, 02 Mar 2023 14:39:24 GMT
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- Kif5a Regulates Mitochondrial Transport in Developing Retinal Ganglion
Cells In Vitro-
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Abstract: Purpose Axon transport of organelles and neurotrophic factors is necessary for maintaining cellular function and survival of retinal ganglion cells (RGCs). However, it is not clear how trafficking of mitochondria, essential for RGC growth and maturation, changes during RGC development. The purpose of this study was to understand the dynamics and regulation of mitochondrial transport during RGC maturation using acutely purified RGCs as a model system. Methods Primary RGCs were immunopanned from rats of either sex during three stages of development. MitoTracker dye and live-cell imaging were used to quantify mitochondrial motility. Analysis of single-cell RNA sequencing was used to identify Kinesin family member 5A (Kif5a) as a relevant motor candidate for mitochondrial transport. Kif5a expression was manipulated with either short hairpin RNA (shRNA) or exogenous expression adeno-associated virus viral vectors. Results Anterograde and retrograde mitochondrial trafficking and motility decreased through RGC development. Similarly, the expression of Kif5a, a motor protein that transports mitochondria, also decreased during development. Kif5a knockdown decreased anterograde mitochondrial transport, while Kif5a expression increased general mitochondrial motility and anterograde mitochondrial transport. Conclusions Our results suggested that Kif5a directly regulates mitochondrial axonal transport in developing RGCs. Future work exploring the role of Kif5a in vivo in RGCs is indicated.
PubDate: Thu, 02 Mar 2023 14:39:24 GMT
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- The RNA m 5 C Methylase NSUN2 Modulates Corneal Epithelial Wound Healing
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Abstract: Purpose The emerging epitranscriptomics offers insights into the physiopathological roles of various RNA modifications. The RNA methylase NOP2/Sun domain family member 2 (NSUN2) catalyzes 5-methylcytosine (m5C) modification of mRNAs. However, the role of NSUN2 in corneal epithelial wound healing (CEWH) remains unknown. Here we describe the functional mechanisms of NSUN2 in mediating CEWH. Methods RT-qPCR, Western blot, dot blot, and ELISA were used to determine the NSUN2 expression and overall RNA m5C level during CEWH. NSUN2 silencing or overexpression was performed to explore its involvement in CEWH both in vivo and in vitro. Multi-omics was integrated to reveal the downstream target of NSUN2. MeRIP-qPCR, RIP-qPCR, and luciferase assay, as well as in vivo and in vitro functional assays, clarified the molecular mechanism of NSUN2 in CEWH. Results The NSUN2 expression and RNA m5C level increased significantly during CEWH. NSUN2 knockdown significantly delayed CEWH in vivo and inhibited human corneal epithelial cells (HCEC) proliferation and migration in vitro, whereas NSUN2 overexpression prominently enhanced HCEC proliferation and migration. Mechanistically, we found that NSUN2 increased ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) translation through the binding of RNA m5C reader Aly/REF export factor. Accordingly, UHRF1 knockdown significantly delayed CEWH in vivo and inhibited HCEC proliferation and migration in vitro. Furthermore, UHRF1 overexpression effectively rescued the inhibitory effect of NSUN2 silencing on HCEC proliferation and migration. Conclusions NSUN2-mediated m5C modification of UHRF1 mRNA modulates CEWH. This finding highlights the critical importance of this novel epitranscriptomic mechanism in control of CEWH.
PubDate: Thu, 02 Mar 2023 14:39:24 GMT
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- The Saccade Main Sequence in Patients With Retinitis Pigmentosa and
Advanced Age-Related Macular Degeneration-
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Abstract: Purpose Most eye-movement studies in patients with visual field defects have examined the strategies that patients use while exploring a visual scene, but they have not investigated saccade kinematics. In healthy vision, saccade trajectories follow the remarkably stereotyped “main sequence”: saccade duration increases linearly with saccade amplitude; peak velocity also increases linearly for small amplitudes, but approaches a saturation limit for large amplitudes. Recent theories propose that these relationships reflect the brain's attempt to optimize vision when planning eye movements. Therefore, in patients with bilateral retinal damage, saccadic behavior might differ to optimize vision under the constraints imposed by the visual field defects. Methods We compared saccadic behavior of patients with central vision loss, due to age-related macular degeneration (AMD), and patients with peripheral vision loss, due to retinitis pigmentosa (RP), to that of controls with normal vision (NV) using a horizontal saccade task. Results Both patient groups demonstrated deficits in saccade reaction times and target localization behavior, as well as altered saccade kinematics. Saccades were generally slower and the shape of the velocity profiles were often atypical, especially in the patients with RP. In the patients with AMD, the changes were far less dramatic. For both groups, saccade kinematics were affected most when the target was in the subjects’ blind field. Conclusions We conclude that defects of the central and peripheral retina have distinct effects on the saccade main sequence, and that visual inputs play an important role in planning the kinematics of a saccade.
PubDate: Wed, 01 Mar 2023 15:15:26 GMT
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