Investigative ophthalmology & visual science最新文献

{"title":"Retinal Function in Advanced Multiple Sclerosis.","authors":"James V M Hanson, Sara Single, Rahel B Eberle, Veronika Kana, Benjamin V Ineichen, Christina Gerth-Kahlert","doi":"10.1167/iovs.65.13.2","DOIUrl":"10.1167/iovs.65.13.2","url":null,"abstract":"<p><strong>Purpose: </strong>People with multiple sclerosis (pwMS) experience autoimmunity-mediated inflammation and neurodegeneration throughout the central nervous system. There remains a need for clinically accessible, reliable functional markers of neurodegeneration in MS. Previous research has described changes to electroretinography (ERG)-derived measures of retinal bipolar cell function in pwMS early in the disease course. We, therefore, investigated ERG as a potential outcome measure in individuals with more advanced disease.</p><p><strong>Methods: </strong>This cross-sectional observational study included pwMS with Expanded Disability Status Scale (EDSS) scores of ≥3.0 and healthy control (HC) participants who underwent ERG, optical coherence tomography, high- and low-contrast visual acuity measurement, and an ophthalmological examination. ERG findings in MS eyes with and without previous optic neuritis (MS +ON; MS -ON) were compared with those in HC eyes. Effects of EDSS, disease duration, ON, and treatment status on selected ERG outcomes were measured. Additional exploratory analyses assessed potential influences of MS phenotype and disease status (clinically active, radiologically active, and disease progression).</p><p><strong>Results: </strong>Delays to two ERG peak times (dark-adapted 3.0 b-wave; light-adapted flicker) were recorded in MS +ON and MS -ON eyes. No influences of EDSS score, disease duration, previous ON, or treatment status were observed. Exploratory analyses were consistent with no effects of MS phenotype or disease status.</p><p><strong>Conclusions: </strong>ERG findings are abnormal in individuals with moderate-severe disability caused by MS; however, these findings are not distinct from those observed earlier in the disease course. Although bipolar dysfunction appears to be common in pwMS throughout the disease course, ERG is likely not useful in monitoring or prognostication of MS.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms Regulating Mitochondrial Transfer in Human Corneal Epithelial Cells.","authors":"Sonali Pal-Ghosh, Beverly A Karpinski, Himani Datta-Majumdar, Soneha Datta, Shelly Dimri, Jordan Hally, Hugo Wehmeyer, Mary Ann Stepp","doi":"10.1167/iovs.65.13.10","DOIUrl":"10.1167/iovs.65.13.10","url":null,"abstract":"<p><strong>Purpose: </strong>The intraepithelial corneal nerves (ICNs) innervating the cornea are essential to corneal epithelial cell homeostasis. Rho-associated kinase (ROCK) inhibitors (RIs) have been reported to play roles in neuron survival after injury and in mitochondrial transfer between corneal epithelial cells. In this study, the mechanisms human corneal limbal epithelial (HCLE) cells use to control intercellular mitochondrial transfer are assessed.</p><p><strong>Methods: </strong>Mitotracker and AAV1 mitotag eGFPmCherry were used to allow us to study mitochondrial transfer between HCLE cells and neurons in co-cultures and in HCLE cultures. A mitochondrial transfer assay was developed using HCLE cells to quantify the impact of cell stress and inhibition of phagocytosis, gap junctions, and ROCK on mitochondrial transfer, cell adhesion, migration, matrix deposition, and mitochondrial content.</p><p><strong>Results: </strong>Bidirectional mitochondrial transfer occurs between HCLE cells and neurons. Mitochondrial transfer among HCLE cells is inhibited when gap junction function is reduced and enhanced by acid stress and by inhibition of either phagocytosis or ROCK. Media conditioned by RI-treated cells stimulates cell adhesion and mitochondrial transfer.</p><p><strong>Conclusions: </strong>Maximal mitochondrial transfer takes place when gap junctions are functional, when ROCK and phagocytosis are inhibited, and when cells are stressed by low pH media. Treatments that reduce mitochondrial content increase HCLE cell mitochondrial transfer. ROCK inhibition in co-cultures causes the release and adhesion of mitochondria to substrates where they can be engulfed by migrating HCLE cells and growing axons and their growth cones.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Microperimetric Features in Bietti Crystalline Dystrophy Patients: A Cross-Sectional Longitudinal Study in a Large Cohort.","authors":"Yufei Xu, Xiao Liu, Nan Wu, Yanling Long, Jiayun Ren, Yu Wang, Xinyi Su, Zengping Liu, Yu Fujinami-Yokokawa, Kaoru Fujinami, Fang Chen, Xiaohong Meng, Yong Liu","doi":"10.1167/iovs.65.13.27","DOIUrl":"10.1167/iovs.65.13.27","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the clinical and genetic characteristics of patients with Bietti crystalline dystrophy (BCD) with a focus on potential of microperimetry in monitoring macular function.</p><p><strong>Methods: </strong>A total of 208 genetically-confirmed BCD patients were enrolled in this retrospective study. The patients were categorized into subgroups based on their fundus characteristics (fovea sparing and fovea involved), optical coherence tomography (OCT) findings (presence/absence of retinal pigment epithelium [RPE] or ellipsoid zone [EZ] line at the fovea/parafovea), and genetic profiles (Mis/Mis, Tru/Mis, Tru/Tru). Fixation patterns were analyzed, and macular sensitivity (MS) parameters were compared among different groups. Longitudinal analysis was performed to calculate the annual changes in MS parameters. Correlation between genotype and phenotype were further investigated by analyzing cumulative incidence of vision impairment among different genotypic groups.</p><p><strong>Results: </strong>Patients with well-preserved RPE or EZ at the foveal/parafoveal region exhibited higher MS. Notably, there was a decline in sensitivity parameters, with a decrease of -2.193 dB/year (95% confidence interval [CI] -4.292 to -0.095, P = 0.041) at the fovea and -1.353 dB/year (95% CI -2.047 to -0.659, P < 0.001) in average sensitivity. An age-adjusted comparison of sensitivity among genotypic groups and cumulative incidence analyses showed no association between genotypic groups and vision loss.</p><p><strong>Conclusions: </strong>Microperimetry proves to be one of a credible tool for detecting macular functional changes in BCD patients. BCD patients with different genotypes may have similar disease progression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"27"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative and Rapid In Vivo Imaging of Human Lenticular Fluorescence.","authors":"Joshua M Herzog, Angela Verkade, Volker Sick","doi":"10.1167/iovs.65.13.41","DOIUrl":"10.1167/iovs.65.13.41","url":null,"abstract":"<p><strong>Purpose: </strong>To quantitatively investigate the chemical origins of near-UV excited fluorescence in the crystalline lens, and demonstrate the potential usefulness of a rapid and noninvasive diagnostic approach for screening and monitoring of lens damage.</p><p><strong>Methods: </strong>Anterior segment UV fluorescence imaging was applied to a population of 30 healthy adults, ages 18 to 64 years. Absolute fluorescence intensities and intensity ratios were compared across the population as a function of age. Fluorescence quantum yield (FQY) was calculated from imaging results based on a previous radiometric characterization.</p><p><strong>Results: </strong>Typical FQYs at 365 nm excitation are approximately 0.2% for healthy adults. Intensity and FQY were observed to increase significantly with age, consistent with ex vivo and confocal microscopy studies. The ratio of blue to green fluorescence is strongly correlated with FQY and age, suggesting that both increases in fluorophore concentration and changes in composition occur with age. Fluorescence data is quantitatively and qualitatively consistent with pyridine nucleotides in young adults, and changes with age are consistent with formation of β-carbolines or advanced glycation end products. Intralens variation is consistent with increased oxidation or glycation in the lens nucleus relative to the cortex.</p><p><strong>Conclusions: </strong>Lenticular fluorescence can be measured rapidly, accurately, and quantitatively in vivo which provides a spatially resolved, quantitative measure of lens chemistry, including damage from oxidation and glycation. Careful interpretation of fluorescence intensities and intensity ratios can provide chemical insight into lens health. Anterior segment UV fluorescence imaging can thus serve as a useful tool for screening, monitoring, and research of lens damage and cataract formation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"41"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Intraocular Concentration of Fibrinogen Regulates Retinal Function Via the ICAM-1 Pathway.","authors":"Yasuyuki Sotani, Hisanori Imai, Hiroko Yamada, Akiko Miki, Sentaro Kusuhara, Makoto Nakamura","doi":"10.1167/iovs.65.13.34","DOIUrl":"10.1167/iovs.65.13.34","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR) is a significant complication of diabetes mellitus that can lead to progressive visual impairment. This study aimed to elucidate the role of fibrinogen, a protein whose serum and intraocular concentrations are elevated in patients with diabetes and DR, in the pathogenesis of DR.</p><p><strong>Methods: </strong>The changes in the protein levels of the neuronal marker tubulin-β3 (TUBB3) and retinal response induced by the intravitreal injections of 1× phosphate-buffered saline, 40 mg/mL of fibrinogen, and 40 mg/mL of fibrinogen in combination with anti-intracellular adhesion molecule-1 (ICAM-1) antibody in normal mice were observed using immunofluorescence, western blotting, and electroretinography.</p><p><strong>Results: </strong>High concentrations of fibrinogen led to a decrease in the expression of TUBB3 in immunofluorescence and western blotting. The amplitudes of the positive scotopic threshold response and b-wave were notably reduced after the injection of fibrinogen, indicating potential damage to the retinal ganglion cells. The co-administration of anti-ICAM-1 antibody effectively mitigated these fibrinogen-induced changes, indicating that fibrinogen-induced damage is mediated via the ICAM-1 pathway.</p><p><strong>Conclusions: </strong>The present study underscores the significance of elevated intraocular fibrinogen levels as a pathogenic factor in DR. Involvement of the fibrinogen/ICAM-1 pathway presents new avenues for therapeutic intervention, especially in patients with treatment-resistant conditions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cysteine Leukotriene Receptor Antagonist-Montelukast Effects on Diabetic Retinal Microvascular Endothelial Cells Curtail Autophagy.","authors":"Ahmed M Awad, Amritha T M Seetharaman, Mohammad Shahadat Hossain, Sally L Elshaer, Rania R Abdelaziz, Manar A Nader, Rajashekhar Gangaraju","doi":"10.1167/iovs.65.13.15","DOIUrl":"10.1167/iovs.65.13.15","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic macular edema (DME) is the primary cause of vision impairment in diabetic retinopathy (DR) patients. A previous study has shown the efficacy of montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, in a diabetic mouse model. This study aims to understand the CysLTR1 signaling in retinal endothelial cells and the impact of montelukast.</p><p><strong>Methods: </strong>Primary human retinal microvascular endothelial cells (HRECs) challenged with 20 ng/mL TNF-α and 30 mM D-glucose (D-glu) for six to 24 hours served as a model of endothelial activation. HRECs were incubated with L-glucose (L-glu) as an osmotic control. CysLTR1 knockdown and montelukast pretreatment assessed CysLTR1 antagonism. Gene expression, protein expression, and cell-permeable dyes were utilized to measure autophagy and inflammation. Transendothelial electrical resistance (TER) and transendothelial migration of mononuclear leukocytes across HRECs monolayer were measured as a functional assessment of vascular permeability.</p><p><strong>Results: </strong>Endothelial activation induced by hyperglycemia and inflammation increased CysLTR1 expression, triggering autophagy within two to six hours, IL-1β production, loss of junction integrity, decreased TER, and increased leukocyte migration within six to 24 hours. Pretreatment with montelukast effectively alleviated these effects, demonstrating its dependence on CysLTR1.</p><p><strong>Conclusions: </strong>Dysfunctional retinal endothelium initiates a self-reinforcing loop of inflammation, autophagy, and compromised integrity associated with heightened CysLTR1 levels. The antagonistic effect of montelukast against CysLTR1 effectively mitigates these detrimental changes. This study reveals CysLTR1 as a potential therapeutic target in treating DME and offers a novel strategy to mitigate detrimental changes in DR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum in: Smoking, Corneal Biomechanics, and Glaucoma: Results From Two Large Population-Based Cohorts.","authors":"","doi":"10.1167/iovs.65.13.18","DOIUrl":"10.1167/iovs.65.13.18","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing IOP-Induced Scleral Deformations in the Myopic and Myopic Glaucoma Spectrums.","authors":"Thanadet Chuangsuwanich, Tin A Tun, Fabian A Braeu, Rachel S Chong, Xiaofei Wang, Ching-Lin Ho, Tin Aung, Michaël J A Girard, Quan V Hoang","doi":"10.1167/iovs.65.13.54","DOIUrl":"10.1167/iovs.65.13.54","url":null,"abstract":"<p><strong>Purpose: </strong>To compare changes in macular curvature following acute IOP elevation across a range of myopic conditions.</p><p><strong>Methods: </strong>We studied 328 eyes from 184 subjects, comprising 32 emmetropic controls (between +2.75 and -2.75 diopters), 50 eyes with high myopia (<-5 diopters; HM), 108 highly myopic with glaucoma (HMG) and 105 pathologic myopia (PM) eyes, and 33 PM with staphyloma (PM+S) eyes. For each eye, we imaged the macula using optical coherence tomography (OCT) under the baseline condition and under acute IOP elevation (to ∼40 mm Hg) achieved through ophthalmodynamometry. We manually aligned the scans (baseline and IOP elevation) using three vascular landmarks in the macula tissue. We then automatically segmented the sclera and the choroid tissues using a deep learning algorithm and extracted the sclera-choroid interface. We calculated the macula curvatures, determined by the radius of curvature of the sclera-choroid interface in the nasal-temporal and superior-inferior direction. Differences in macula curvatures between baseline and elevated IOP scans were calculated at corresponding locations, and the mean curvature difference was reported for each eye.</p><p><strong>Results: </strong>IOP elevation resulted in a significantly higher macula curvature change along the nasal-temporal direction in the PM+S (13.5 ± 8.2 × 10-5 µm-1), PM (9.0 ± 7.9 × 10-5 µm-1), and HMG (5.2 ± 5.1 × 10-5 µm-1) eyes as compared to HM (3.1 ± 2.7 × 10-5 µm-1) eyes (all P < 0.05). Interestingly, HM and HMG eyes had the same curvature change in the nasal-temporal direction as emmetropic control eyes (4.2 ± 4.3 × 10-5 µm-1).</p><p><strong>Conclusions: </strong>Our findings indicate that the macula in HMG, PM, and PM+S eyes showed greater curvature changes under IOP elevation compared to HM and emmetropic eyes. These preliminary results suggest that HM eyes with conditions such as glaucoma or staphyloma are more sensitive to acute IOP elevation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"54"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Cellular Basis of Impaired Phagocytosis and Photoreceptor Degeneration in CLN3 Disease.","authors":"Jimin Han, Sueanne Chear, Jana Talbot, Vicki Swier, Clarissa Booth, Cheyenne Reuben-Thomas, Sonal Dalvi, Jill M Weimer, Alex W Hewitt, Anthony L Cook, Ruchira Singh","doi":"10.1167/iovs.65.13.23","DOIUrl":"10.1167/iovs.65.13.23","url":null,"abstract":"<p><strong>Purpose: </strong>CLN3 Batten disease (also known as juvenile neuronal ceroid lipofuscinosis) is a lysosomal storage disorder that typically initiates with retinal degeneration but is followed by seizure onset, motor decline and premature death. Patient-derived CLN3 disease induced pluripotent stem cell-RPE cells show defective phagocytosis of photoreceptor outer segment (POS). Because modifier genes are implicated in CLN3 disease, our goal here was to investigate a direct link between CLN3 mutation and POS phagocytosis defect.</p><p><strong>Methods: </strong>Isogenic control and CLN3 mutant stem cell lines were generated by CRISPR-Cas9-mediated biallelic deletion of exons 7 and 8. A transgenic CLN3Δ7-8/Δ7-8 (CLN3) Yucatan miniswine was also used to study the impact of CLN3Δ7-8/Δ7-8 mutation on POS phagocytosis. POS phagocytosis by cultured RPE cells was analyzed by Western blotting and immunohistochemistry. Electroretinogram, optical coherence tomography and histological analysis of CLN3Δ7-8/Δ7-8 and wild-type miniswine eyes were carried out at 6, 36, or 48 months of age.</p><p><strong>Results: </strong>CLN3Δ7-8/Δ7-8 RPE (CLN3 RPE) displayed decreased POS binding and consequently decreased uptake of POS compared with isogenic control RPE cells. Furthermore, wild-type miniswine RPE cells phagocytosed CLN3Δ7-8/Δ7-8 POS less efficiently than wild-type POS. Consistent with decreased POS phagocytosis, lipofuscin/autofluorescence was decreased in CLN3 miniswine RPE at 36 months of age and was followed by almost complete loss of photoreceptors at 48 months of age.</p><p><strong>Conclusions: </strong>CLN3Δ7-8/Δ7-8 mutation (which affects ≤85% of patients) affects both RPE and POS and leads to photoreceptor cell loss in CLN3 disease. Furthermore, both primary RPE dysfunction and mutant POS independently contribute to impaired POS phagocytosis in CLN3 disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"23"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Electroretinogram I-Wave, a Component Originating in the Retinal OFF-Pathway, Associates With a Myopia Genetic Risk Polymorphism.","authors":"Zihe Xu, Jit Kai Tan, Krishnika Vetrivel, Xiaofan Jiang, Shaun M Leo, Taha Bhatti, Ambreen Tariq, Andrew R Webster, Anthony G Robson, Christopher J Hammond, Pirro G Hysi, Omar A Mahroo","doi":"10.1167/iovs.65.13.21","DOIUrl":"10.1167/iovs.65.13.21","url":null,"abstract":"<p><strong>Purpose: </strong>One of the strongest genetic associations with myopia is near the GJD2 gene. Recently, this locus was associated with cone-driven electroretinograms (ERGs), with findings highlighting OFF pathway signals specifically. The ERG i-wave is thought to originate in retinal OFF pathways. We explored this component and tested the hypothesis that it would be associated with the myopia risk locus.</p><p><strong>Methods: </strong>International standard LA3 ERGs, recorded with conductive fiber electrodes, were analyzed, first from patients with rare monogenic deficits impairing the ON pathway, or both ON and OFF pathways, to explore effects on the i-wave. Responses were then analyzed from adult participants from the TwinsUK cohort: i-wave amplitudes were measured by two investigators independently, blinded to genotype at the GJD2 locus. We investigated the association between i-wave amplitude and allelic identity at this locus, adjusting for age, sex, and familial relatedness.</p><p><strong>Results: </strong>Patient recordings showed the i-wave persisted in the absence of ON pathway signals, but was abolished when both ON and OFF pathways were impaired. For TwinsUK participants, recordings and genotypes were available in 184 individuals (95% female participants; mean standard deviation [SD] age, 64.1 [9.7] years). Mean (SD) i-wave amplitude was 14.5 (SD = 6.5) microvolts. Allelic dosage at the risk locus was significantly associated with i-wave amplitude (P = 0.027).</p><p><strong>Conclusions: </strong>Patient ERGs were consistent with the i-wave arising from cone-driven OFF pathways. Amplitudes associated significantly with allelic dosage at the myopia risk locus, supporting the importance of cone-driven signaling in myopia development and further highlighting relevance of the OFF pathway in relation to this locus.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"21"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}