Investigative ophthalmology & visual science最新文献

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Diabetes-Induced Dysregulation of Peripapillary and Macular Neurovascular Units. 糖尿病引起的乳头周围和黄斑神经血管单位的失调。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.10
Mizuho Mitamura, Satoru Kase, Hiroaki Endo, Michiyuki Saito, Satoshi Katsuta, Susumu Ishida
{"title":"Diabetes-Induced Dysregulation of Peripapillary and Macular Neurovascular Units.","authors":"Mizuho Mitamura, Satoru Kase, Hiroaki Endo, Michiyuki Saito, Satoshi Katsuta, Susumu Ishida","doi":"10.1167/iovs.66.9.10","DOIUrl":"https://doi.org/10.1167/iovs.66.9.10","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to investigate the impact of diabetic retinopathy (DR) on macular and peripapillary neurovascular units (NVUs) by assessing optical coherence tomography (OCT)/OCT angiography-based macular and peripapillary NVU parameters.</p><p><strong>Methods: </strong>This study enrolled 182 eyes with type 2 diabetes mellitus (DM) eyes and 202 healthy control eyes. The eyes of DM patients were divided into DM without DR (DM/noDR; n = 136) and DR stage groups (n = 46). Macular NVU parameters consisted of ganglion cell-inner plexiform layer (GCIPL) thickness and macular perfusion density (PD). As for peripapillary NVU parameters, peripapillary retinal nerve fiber layer (RNFL) thickness, together with radial peripapillary capillary perfusion density (RPC-PD) and RPC flux index (RPC-FI), represented by peripapillary structural and functional vascular parameters, were also examined. Macular and peripapillary parameters were compared among three stages, and correlations between macular and peripapillary parameters were examined for each stage.</p><p><strong>Results: </strong>Macular GCIPL thickness and macular PD decreased with stage progression, preserving positive correlations (i.e., preserving macular NVU) with each other in all eyes, but correlation coefficients were the lowest in DM/noDR eyes. Macular GCIPL thickness, as well as macular PD, positively correlated with peripapillary NVU parameters over the entire stages except macular PD and RNFL thickness in DR eyes (i.e., preserving macular and peripapillary NVU), but correlation coefficients were the lowest in DM/noDR eyes.</p><p><strong>Conclusions: </strong>Macular and peripapillary NVU were preserved throughout the stages: control, DM/noDR, and DR groups, but the linkage weakened at the onset of DM, suggesting diabetes-induced dysregulation of macular and peripapillary NVUs in subclinical DR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553589","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}
引用次数: 0
Polygenic Risk Prediction for Normal-Tension Glaucoma. 常压型青光眼的多基因风险预测。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.4
Maryam Marzban, Santiago Diaz Torres, Regina Yu, Weixiong He, David A Mackey, Ayellet V Segrè, Janey Wiggs, Stuart MacGregor, Puya Gharahkhani
{"title":"Polygenic Risk Prediction for Normal-Tension Glaucoma.","authors":"Maryam Marzban, Santiago Diaz Torres, Regina Yu, Weixiong He, David A Mackey, Ayellet V Segrè, Janey Wiggs, Stuart MacGregor, Puya Gharahkhani","doi":"10.1167/iovs.66.9.4","DOIUrl":"10.1167/iovs.66.9.4","url":null,"abstract":"<p><strong>Purpose: </strong>Normal-tension glaucoma (NTG) is a subtype of glaucoma characterized by optic nerve damage in the setting of normal intraocular pressure. Polygenic risk scores (PRSs) have shown potential to assist with risk prediction in glaucoma, but to date no comprehensive studies have evaluated the predictive ability of PRSs for NTG.</p><p><strong>Methods: </strong>We utilized genome-wide association study (GWAS) summary data for NTG from a European cohort to estimate the variant weights and construct PRSs. The PRSs were computed using both the SBayesRC and clumping and thresholding (C+T) methods in 317 European ancestry NTG cases and 634 controls from the National Institutes of Health All of Us dataset. To validate our findings, we used the Genetics of Glaucoma (GOG) dataset for NTG cases (n = 89) and the QSkin Sun and Health Study (QSkin) dataset for controls (n = 267).</p><p><strong>Results: </strong>We applied the SBayesRC method, which incorporates genome functional annotation, to compare results across both studies. Logistic regression was performed to assess the association between PRSs and NTG. SBayesRC analysis demonstrated that the NTG PRS was significantly associated with NTG, yielding an odds ratio per standard deviation of 1.53 (95% confidence interval [CI], 1.32-1.77; P = 6.86 × 10⁻9) in the All of Us dataset and 1.83 (95% CI, 1.42-2.38; P = 4.01 × 10⁻6) in the combined GOG and QSkin dataset. The C+T method produced results similar to those for SBayesRC.</p><p><strong>Conclusions: </strong>Despite the limited sample size of current NTG GWASs, our findings suggest that NTG-specific PRSs hold promise for risk prediction. Future large-scale GWASs for NTG may enable the development of clinically relevant PRSs, improving early detection and personalized risk assessment for this challenging phenotype.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540234","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}
引用次数: 0
Evidence for M2 Muscarinic Receptor Antagonist Delay of Myopia Development Through Activation of Kir3.4 Channel in the Retina of Guinea Pigs. M2毒蕈碱受体拮抗剂通过激活豚鼠视网膜Kir3.4通道延缓近视发展的证据。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.5
Hong Zhou, Guimei Zhou, Qin Yang, Jiahao Niu, Runzhe Wang, Huilan Liu, Suwen Hou, Hongsheng Bi, Xuan Liao
{"title":"Evidence for M2 Muscarinic Receptor Antagonist Delay of Myopia Development Through Activation of Kir3.4 Channel in the Retina of Guinea Pigs.","authors":"Hong Zhou, Guimei Zhou, Qin Yang, Jiahao Niu, Runzhe Wang, Huilan Liu, Suwen Hou, Hongsheng Bi, Xuan Liao","doi":"10.1167/iovs.66.9.5","DOIUrl":"10.1167/iovs.66.9.5","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the association between muscarinic receptor M2 and potassium channel Kir3.4 encoded by gene KCNJ5, as well as their role in guinea pigs with form deprivation myopia (FDM).</p><p><strong>Methods: </strong>One hundred sixty-five 3-week-old guinea pigs were randomly assigned to the following groups: normal control (NC), self-control (SC), form deprivation (FD), lentiviral vector (FD + Vector), KCNJ5 overexpression lentivirus (FD + KCNJ5-OE), vehicle control (FD + DMSO), M2 receptor antagonist (FD + AF-DX 116), and M2 receptor agonist (FD + LY2119620). The association between M2 receptors and retinal potassium channels and effects of retinal K+ concentration on myopia development were investigated by constructing a lentiviral KCNJ5 overexpression and M2 receptor intervention model. Immunohistochemistry and molecular assays were conducted to measure the distribution and expression of Kir3.4-related mRNA and protein in the retina. TUNEL was used to observe the drug toxicity response on the retina.</p><p><strong>Results: </strong>The FD group had higher myopic degree (all P < 0.001) and lower expression levels of Kir3.4 than the NC group (P = 0.008). The FD + KCNJ5-OE group exhibited upregulated Kir3.4 protein expression (P < 0.001), but a significant decrease in myopia degree and K+ concentration (all P < 0.001) compared with the FD + Vector group. The FD + AF-DX 116 group exhibited lower myopic degree, K+ concentration (all P < 0.05), and higher Kir3.4 protein expression (P < 0.001), as well as the FD + LY2119620 group exhibited significantly upregulated myopia degree and K+ concentration (all P < 0.001) compared with the FD + DMSO group.</p><p><strong>Conclusions: </strong>This study is the first to explore the muscarinic receptor-potassium channel connection and its implications in the development of myopia. The M2 receptor may be involved in the development of myopia by regulating retinal Kir3.4 channel and K+ homeostasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540230","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}
引用次数: 0
Fundus Refraction Offset as a Personalized Biomarker for 12-Year Risk of Retinal Detachment. 眼底屈光偏移作为12年视网膜脱离风险的个性化生物标志物。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.1
Fabian Yii, Ian J C MacCormick, Niall Strang, Miguel O Bernabeu, Tom MacGillivray
{"title":"Fundus Refraction Offset as a Personalized Biomarker for 12-Year Risk of Retinal Detachment.","authors":"Fabian Yii, Ian J C MacCormick, Niall Strang, Miguel O Bernabeu, Tom MacGillivray","doi":"10.1167/iovs.66.9.1","DOIUrl":"10.1167/iovs.66.9.1","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the potential of a novel anatomical metric of ametropia-fundus refraction offset (FRO)-in stratifying the risk of retinal detachment (RD) or breaks, beyond the influence of risk factors including spherical equivalent refraction (SER).</p><p><strong>Methods: </strong>Participants from the UK Biobank with no prior history of RD/breaks were analyzed (n = 9320). The onset of RD/breaks over a 12-year follow-up period was determined based on linked healthcare data. A previously trained deep learning model was applied to each fundus photograph to predict SER. FRO was defined as the error in the fundus-predicted SER, with a negative value indicating a relatively myopic-looking fundus. Cox regression was used to examine the association of baseline FRO with RD/breaks-adjusting for baseline SER, baseline age, sex, and cataract surgery during follow-up. In a subgroup of participants (n = 7127) with high-quality optical coherence tomography scans, we additionally adjusted for baseline macular thickness (MT). All analyses initially considered any RD/breaks as the event, followed by rhegmatogenous RD/breaks.</p><p><strong>Results: </strong>The mean (SD) baseline age was 54.8 (8.2) years. Sixty-four participants developed RD/breaks (of any subcategory), with a mean (SD) of 7.0 (3.3) years between baseline and disease onset. A more negative baseline FRO was independently associated with an increased risk of any RD/breaks (adjusted hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.50-0.87, P = 0.003) and rhegmatogenous RD/breaks (HR = 0.61, 95% CI = 0.45-0.82, P = 0.001). Similar independent associations were evident in the subgroup analysis that additionally adjusted for MT.</p><p><strong>Conclusions: </strong>A more negative baseline FRO is associated with a higher risk of developing RD/breaks, even among individuals with similar baseline SER and other risk factors. This demonstrates a potential benefit of shifting towards an anatomic definition of myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540231","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}
引用次数: 0
IMI-Instrumentation for Myopia Management. imi -近视管理仪器。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.7
Deborah Jones, Amy Chow, Daddi Fadel, Jose Manuel Gonzalez Meijome, Andrzej Grzybowski, Pete Kollbaum, James Loughman, James Wolffsohn
{"title":"IMI-Instrumentation for Myopia Management.","authors":"Deborah Jones, Amy Chow, Daddi Fadel, Jose Manuel Gonzalez Meijome, Andrzej Grzybowski, Pete Kollbaum, James Loughman, James Wolffsohn","doi":"10.1167/iovs.66.9.7","DOIUrl":"10.1167/iovs.66.9.7","url":null,"abstract":"<p><p>The rising prevalence of myopia has underscored the importance of early diagnosis and effective management strategies to control its progression and to prevent complications. Advancements in instrumentation enable clinicians to provide individualized evidence-based care for patients. Instrumentation for myopia control encompasses a wide range of technologies designed to assess refractive error, biometric parameters, including axial length, accommodative responses, as well as detailed assessment of ocular health. These tools offer clinicians the ability to move beyond traditional clinical techniques, providing more accurate, detailed, and repeatable measurements critical for the detection and monitoring of myopia progression. This allows for a personalized approach to treatment planning, enabling the selection and optimization of myopia control interventions. Furthermore, advanced imaging and real-time data visualization support patient education by fostering understanding, which may improve adherence to treatment plans. By adopting these technologies, clinicians can address the complexities of myopia management, deliver precise and effective care, and contribute to global efforts to curb the myopia epidemic. The integration of advanced instrumentation into clinical practice encourages early intervention and management strategies for patients at risk of becoming myopic (pre-myopia), as well as improving patient outcomes for myopic patients.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540232","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}
引用次数: 0
The Effect of Carotid Atherosclerosis on the Risk for Open-Angle Glaucoma. 颈动脉粥样硬化对开角型青光眼风险的影响。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.9
Victor A de Vries, Karin A van Garderen, Caroline C W Klaver, Daniel Bos, Maryam Kavousi, Wishal D Ramdas
{"title":"The Effect of Carotid Atherosclerosis on the Risk for Open-Angle Glaucoma.","authors":"Victor A de Vries, Karin A van Garderen, Caroline C W Klaver, Daniel Bos, Maryam Kavousi, Wishal D Ramdas","doi":"10.1167/iovs.66.9.9","DOIUrl":"10.1167/iovs.66.9.9","url":null,"abstract":"<p><strong>Purpose: </strong>There is evidence that patients with open-angle glaucoma (OAG) have altered hemodynamic parameters of the carotid and retinal arteries. We investigated the effect of carotid artery atherosclerosis on incident OAG, intraocular pressure (IOP), and macular retinal nerve fiber layer (mRNFL) in the general population.</p><p><strong>Methods: </strong>We analyzed data from the Rotterdam Study, a large prospective population-based cohort study. Carotid atherosclerosis was assessed by measuring the carotid intima-media thickness (cIMT). We used multivariable Cox proportional hazard models to estimate the effect of cIMT on OAG risk, and linear mixed models for IOP and mRNFL. Linear and logistic regressions were used to analyze within participants with OAG the effect of cIMT on age at diagnosis and the requirement for glaucoma surgery.</p><p><strong>Results: </strong>Among 9652 participants, 193 developed OAG during 89,665 person-years of follow-up (mean follow-up = 10.5 years). Each standard deviation increase in cIMT was associated with a 17% higher risk of developing OAG (adjusted hazard ratio = 1.17, 95% confidence interval [CI] = 1.00 to 1.36, P = 0.047). Although no association between cIMT and IOP was found, the mRNFL thickness decreased by an average of 0.17 µm (95% CI = 0.01 to 0.34) for each standard deviation increase in cIMT. Among participants with OAG, an increased cIMT was also associated with a younger age at diagnosis (beta = -1.01 years, 95% CI = -1.84 to -0.17), and more frequent requirement of glaucoma surgery (odds ratio [OR] = 1.93, 95% CI = 1.07 to 3.50).</p><p><strong>Conclusions: </strong>Among participants with OAG, an increased cIMT was associated with a younger age at diagnosis. In patients with OAG and unexplained continuous progression, a screening ultrasound examination of the carotid arteries might be considered.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"9"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540236","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}
引用次数: 0
Axial Length Dynamics and Safety of Occlusion Therapy in Pediatric Amblyopia: A Longitudinal Analysis. 儿童弱视的眼轴长度动态和闭锁治疗的安全性:一项纵向分析。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.12
Wentong Yu, Yunsi He, Xuan Qiu, Ying Yao, Qingqing Ye, Lei Feng, Zixuan Xu, Yusong Zhou, Yangfei Pang, Yudan Zhong, Qiuying Li, Junpeng Yuan, Yun Wen, Jinrong Li
{"title":"Axial Length Dynamics and Safety of Occlusion Therapy in Pediatric Amblyopia: A Longitudinal Analysis.","authors":"Wentong Yu, Yunsi He, Xuan Qiu, Ying Yao, Qingqing Ye, Lei Feng, Zixuan Xu, Yusong Zhou, Yangfei Pang, Yudan Zhong, Qiuying Li, Junpeng Yuan, Yun Wen, Jinrong Li","doi":"10.1167/iovs.66.9.12","DOIUrl":"https://doi.org/10.1167/iovs.66.9.12","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the impact of occlusion therapy on the elongation of axial length in children with amblyopia using real-world big data.</p><p><strong>Methods: </strong>A cohort of 2932 children aged 3 to 15 years undergoing occlusion therapy with varying patching durations was analyzed using longitudinal data from the Zhongshan Ophthalmic Center (May 1, 2019 to September 30, 2023). Retrospective analyses utilized multivariable linear regression to assess associations between patching duration and axial length elongation. Generalized estimating equations (GEEs) were used to evaluate interocular axial length differences. The analyses were adjusted for factors including revisit interval, age, sex, baseline best-corrected visual acuity (BCVA), initial axial length, spherical equivalent, amblyopia type, and concurrent treatments.</p><p><strong>Results: </strong>The mean annual axial length increase was 0.23 ± 0.22 mm. Patching had no significant overall effect on axial length elongation (β = -0.02, P = 0.12), even for long daily patching (≥5 hours/day). Subgroup analyses revealed reduced axial length elongation in patched eyes of school-age children (6-12 years) with shorter baseline axial lengths, suggesting age- and baseline-specific effects. GEE analysis showed no significant interocular differences except among preschool children (3-5 years), where the observed eyes exhibited slightly less axial length elongation compared with fellow eyes.</p><p><strong>Conclusions: </strong>Occlusion therapy is safe for amblyopia management. Tailored regimens based on age and baseline ocular characteristics are recommended to optimize therapeutic outcomes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553588","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}
引用次数: 0
A Phenotypic Study of CRB1 Retinopathy Secondary to the Variant p.(Pro836Thr) Prevalent in Those of Black African Ancestry. 在非洲黑人祖先中流行的变异p.(Pro836Thr)继发的CRB1视网膜病变的表型研究
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.3
Wendy M Wong, Anthony G Robson, Rebecca A Baker, Gavin Arno, Joseph Van Aerschot, Siying Lin, Mariya Moosajee, Michel Michaelides, Omar A Mahroo, Andrew R Webster
{"title":"A Phenotypic Study of CRB1 Retinopathy Secondary to the Variant p.(Pro836Thr) Prevalent in Those of Black African Ancestry.","authors":"Wendy M Wong, Anthony G Robson, Rebecca A Baker, Gavin Arno, Joseph Van Aerschot, Siying Lin, Mariya Moosajee, Michel Michaelides, Omar A Mahroo, Andrew R Webster","doi":"10.1167/iovs.66.9.3","DOIUrl":"10.1167/iovs.66.9.3","url":null,"abstract":"<p><strong>Purpose: </strong>To comprehensively characterize the clinical consequences of the CRB1 variant p.(Pro836Thr). In African populations, this variant has an allele frequency of 0.329% (gnomAD v4.1.0).</p><p><strong>Methods: </strong>This study was a retrospective case series of 14 patients from 11 families with molecularly confirmed CRB1-associated retinal dystrophy, each possessing at least one p.(Pro836Thr) variant. The age at onset of visual symptoms, best-corrected visual acuity, imaging findings, and quantitative electrophysiologic measurements of retinal function were analyzed.</p><p><strong>Results: </strong>The p.(Pro836Thr) variant was homozygous in four families and compound heterozygous in seven families. The familial origins included Nigeria (n = 4), Ghana (n = 3), the Caribbean region (n = 2), and Uganda (n = 1). The median follow-up was 7 years (interquartile range, 3-16). Symptom onset was most common in childhood (eight patients, 57.1%). Reduced central vision was the most frequent presenting symptom (12 patients, 85%). Widefield multimodal imaging revealed peripheral retinal changes in addition to macular changes in three patients. Nine patients had international standard electrophysiology and showed generalized retinal dysfunction with a similar degree of rod and cone system involvement (n = 7) or a clear rod-cone pattern of dysfunction (n = 2). All had pattern electroretinography (ERG) evidence of macular dysfunction.</p><p><strong>Conclusions: </strong>The study highlights the association of the p.(Pro836Thr) variant with African ancestry and characterizes their key clinical and electrophysiological features. Our study suggests that the p.(Pro836Thr) variant confers a less severe consequence on retinal function and structure than the majority of other reported CRB1 variants. Although retinal imaging may show alterations confined to the macular region, electrophysiology in this series indicates generalized cone and rod photoreceptor dysfunction.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540229","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}
引用次数: 0
Inhibitor of DNA-Binding 3 Is a Novel Regulator of Limbal Epithelial Cell Migration Via the EphA2/Akt Signaling Pathway. dna结合3抑制剂通过EphA2/Akt信号通路调控角膜缘上皮细胞迁移
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.2
Elwin D Clutter, Wending Yang, Jacob Han, Nihal Kaplan, Han Peng
{"title":"Inhibitor of DNA-Binding 3 Is a Novel Regulator of Limbal Epithelial Cell Migration Via the EphA2/Akt Signaling Pathway.","authors":"Elwin D Clutter, Wending Yang, Jacob Han, Nihal Kaplan, Han Peng","doi":"10.1167/iovs.66.9.2","DOIUrl":"10.1167/iovs.66.9.2","url":null,"abstract":"<p><strong>Purpose: </strong>Upon corneal injury, early and late transit amplifying (TA) cells, the progeny of epithelial stem cells, migrate to the site of the wound, which facilitates its closure. Understanding the targetable signals that guide such cell migration is essential for the development of novel wound-healing strategies.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was conducted in wild-type cornea. To investigate the role of inhibitor of DNA binding 3 (ID3) in the limbal epithelium, bulk RNA-seq was conducted in limbal epithelial cells with ID3 knockdown. hTCEpi cells were transfected with small interfering RNAs (siRNAs) against ID3, and cell migration was assessed using scratch wound assays.</p><p><strong>Results: </strong>The scRNA-seq revealed that ID3, a transcription factor, was preferentially expressed in the stem/early TA population of limbal epithelium. Bulk RNA-seq in limbal epithelial cells with ID3 knockdown suggested a role of ID3 in cell migration. Scratch wound assays confirmed that loss of ID3 in human limbal epithelial cells markedly accelerated wound sealing, indicating an inhibitory role of ID3 in cell migration. Gene Ontology analysis of the RNA-seq data suggested that ID3 negatively regulates EphA2 (a receptor tyrosine kinase) and Akt signaling, both of which have a critical role in cell migration. Consistently, loss of ID3 induced ligand-independent activation of EphA2, as well as enhanced phosphorylation of Akt proteins. Scratch wound assays demonstrated that both ligand-independent activation of EphA2 and phosphorylation of Akt were required for enhanced cell migration in cells lacking ID3.</p><p><strong>Conclusions: </strong>Our findings indicate that ID3, EphA2, and Akt form a novel signaling axis, which plays a critical role in corneal epithelial wound healing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540233","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}
引用次数: 0
Quantitative Choroidal Analysis of Molecularly Characterized Retinitis Pigmentosa. 分子特征视网膜色素变性的脉络膜定量分析。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-07-01 DOI: 10.1167/iovs.66.9.11
Kirk A J Stephenson, Tiffany Tse, Jiwon Hwang, Andrii Kavetskyi, Shanil R Dhanji, Olubayo U Kolawole, Cheryl Y Gregory-Evans, Kaivon Pakzad-Vaezi, Zaid N Mammo, Kevin Gregory-Evans, Myeong Jin Ju
{"title":"Quantitative Choroidal Analysis of Molecularly Characterized Retinitis Pigmentosa.","authors":"Kirk A J Stephenson, Tiffany Tse, Jiwon Hwang, Andrii Kavetskyi, Shanil R Dhanji, Olubayo U Kolawole, Cheryl Y Gregory-Evans, Kaivon Pakzad-Vaezi, Zaid N Mammo, Kevin Gregory-Evans, Myeong Jin Ju","doi":"10.1167/iovs.66.9.11","DOIUrl":"https://doi.org/10.1167/iovs.66.9.11","url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a genetically diverse progressive retinal degeneration with many biomarkers. Detailed retinal phenotypes are described using multimodal imaging, however choroidal characteristics remain ill-defined. We report the first quantitative choroidal evaluation in molecularly characterized RP and assess relationships with retinal structure and function.</p><p><strong>Methods: </strong>Patients with genetically confirmed RP who had optical coherence tomography images and best-corrected visual acuity (BCVA) were assessed. Optical coherence tomography images were manually segmented (ITKSnap) calculating choroidal thickness (CT), choroidal area (CA), and choroidal volume (CV). The choroidal vascularity index (CVI) was calculated with ImageJ. Comparisons were made between X-linked (RPGR), autosomal-recessive (USH2A), and autosomal-dominant (RHO, PRPF31) genotypes, including comparisons for choroidal/retinal parameters, BCVA, and spherical equivalent (SE).</p><p><strong>Results: </strong>Sixty-five patients (mean age, 47.3 ± 19.5 years; 52.3% female) met the inclusion criteria. CT was thinner in RP patients than controls (P = 0.003). A thinner choroid was associated with older age (r = -0.512; P < 0.001) and worse BCVA (r = 0.298, P = 0.002) but not SE (P = 0.194). Although variable, no statistically significant differences were found for choroidal measures between groups. Leptochoroid (≤100 µm) was associated with advanced age (P < 0.001) and worse BCVA (P = 0.032), but not greater myopia (P = 0. 533). Greater CVI was only associated with better BCVA (P < 0.001) and no other parameters.</p><p><strong>Conclusions: </strong>We report the first quantitative choroidal assessment in a cohort with genetically characterized RP. CT changes in RP are not explained solely by age-related choroidal thinning, nor by SE but seem to be dynamic and reactive to degree and rate of retinal degeneration.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"11"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553590","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}
引用次数: 0
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