Investigative ophthalmology & visual science最新文献

{"title":"Erratum in: Comments on \"Real-World Outcomes After Switch From Aflibercept to Faricimab in Eyes With Diabetic Macular Edema\".","authors":"","doi":"10.1167/iovs.66.12.64","DOIUrl":"10.1167/iovs.66.12.64","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"64"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185852","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":"IMI-Interventions for Controlling Myopia Onset and Progression 2025.","authors":"Mark A Bullimore, Kathryn J Saunders, Rigmor C Baraas, David A Berntsen, Zhi Chen, Audrey Wei Lin Chia, So Goto, Jun Jiang, Weizhong Lan, Nicola S Logan, Raymond P Najjar, Jan Roelof Polling, Scott A Read, Emily C Woodman-Pieterse, Noémi Széll, Pavan K Verkicharla, Pei-Chang Wu, Xiaoying Zhu, James Loughman, Manbir Nagra, John R Phillips, Huy D M Tran, Fuensanta A Vera-Diaz, Jason Yam, Yue M Liu, Sarah E Singh, Christine F Wildsoet","doi":"10.1167/iovs.66.12.39","DOIUrl":"10.1167/iovs.66.12.39","url":null,"abstract":"<p><p>Myopia is recognized as a significant public health problem, particularly in East and Southeast Asia. This has led to the development and evaluation of a range of interventions to slow its progression and delay its onset. Since the publication of the 2019 International Myopia Institute's review of interventions for controlling myopia onset and progression, treatment options have continued to grow in number. This article reviews the efficacy of such interventions under five categories: optical, pharmacological, environmental (behavioral), colored light, and surgical. In summarizing the efficacy of mature technologies, only randomized controlled trials were considered, although such data are very limited for emerging treatments. The overall conclusion is that there are multiple effective interventions in most categories. Further research should aim to understand the mechanisms underlying myopia progression and the modalities that slow its progression in order to develop more effective treatments.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"39"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075234","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":"Endothelial-Pericyte Interactions Regulate Angiogenesis Via VEGFR2 Signaling During Retinal Development and Disease.","authors":"Ying-Yu Lin, Emily Warren, Bria L Macklin, Lucas Ramirez, Sharon Gerecht","doi":"10.1167/iovs.66.12.45","DOIUrl":"10.1167/iovs.66.12.45","url":null,"abstract":"<p><strong>Purpose: </strong>Endothelial-pericyte interaction disruption causes vascular dropout and pathological angiogenesis, severely impacting visual function in ocular microvascular diseases. This study examines VEGF receptor 2 (VEGFR2) signaling in endothelial-pericyte interactions, highlighting VEGFR2 as a potential therapeutic target for promoting pericyte coverage and decreasing vascular leakage in diseased retinas.</p><p><strong>Method: </strong>Cell-cell interactions with VEGFR2 signaling were assessed using isogenic endothelial cells and pericytes from induced pluripotent stem cells. We investigated changes in VEGFR2 signaling resulting from endothelial-pericyte interactions using quantitative Reverse Transcription PCR, western blot analysis, immunofluorescence staining, migration assays, permeability assays, transendothelial electrical resistance measurements, flow cytometry, and three-dimensional collagen gel vascular networks. We validated VEGFR2 as a therapeutic target via intravitreal injection in the oxygen-induced retinopathy mouse model. Treatment effects were evaluated using western blot analysis, immunofluorescence staining, and an FITC-dextran permeability assay to assess protein expression, pericyte recruitment, and retinal vascular function in response to VEGFR2 modulation.</p><p><strong>Results: </strong>We demonstrate that direct endothelial-pericyte contact, mediated by N-cadherin, downregulates phosphorylated VEGFR2 in endothelial cells, thereby enhancing pericyte migration and promoting endothelial cell barrier function. Intravitreal injection of a VEGFR2 inhibitor in mouse models of the developing retina and oxygen-induced retinopathy increased pericyte recruitment and decreased vascular leakage. The VEGFR2 inhibitor further rescued ischemic retinopathy by enhancing vascularization and tissue growth.</p><p><strong>Conclusions: </strong>Our findings uncover a novel mechanism by which VEGFR2 signaling is regulated through endothelial-pericyte interactions, promoting pericyte migration and strengthening endothelial barrier function. These results suggest a pathway that could be harnessed to support the growth of functional and mature microvasculature in ocular microvascular diseases and tissue regeneration overall.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"45"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085912","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":"Selective Impairment of Rod-Driven Vision in Vitamin A Deficiency: Insights From Examining the Effect of Desensitizing Backgrounds.","authors":"Megan Margetts, Remi Rufus-Toye, Xiaofan Jiang, Shaun M Leo, Isabelle Chow, Mathura Indusegaran, Pirro G Hysi, Andrew R Webster, Christopher J Hammond, Omar A Mahroo","doi":"10.1167/iovs.66.12.30","DOIUrl":"10.1167/iovs.66.12.30","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to explore whether nyctalopia in vitamin A deficiency (VAD) is attributable to simple reduction in quantal catch or to an \"equivalent background\" phenomenon.</p><p><strong>Methods: </strong>Five individuals were recruited for experimental electroretinograms (ERGs), including three healthy participants (aged 21 to 47 years), one patient with VAD (aged 70 years), and one patient with GNAT2-associated achromatopsia (aged 43 years). Recordings used conductive fiber electrodes and followed dark adaptation and mydriasis. Dim flashes of varying strengths were delivered in the dark to mimic reduction in quantal catch; flashes of fixed strength (0.03 scotopic cd·s/m2) were delivered on dim blue backgrounds.</p><p><strong>Results: </strong>International standard recordings in the patient with VAD showed selective attenuation of dark-adapted responses in severe deficiency, which normalized following treatment. Light-adapted responses did not change. In experimental recordings, both reducing flash strength and applying dim backgrounds reduced ERG amplitude. Reducing flash strength also increased latency of the response, whose rising phase and peak became progressively delayed. Dim backgrounds did not prolong latency. This was seen in all participants, including the patient with achromatopsia, indicating that this was a property of the rod system. In moderate VAD, the dim-flash response was reduced, but not delayed, resembling the response seen in the presence of a dim background.</p><p><strong>Conclusions: </strong>Our findings indicate that rod system desensitization in VAD likely arises from an \"equivalent background\" effect, probably arising from activation of phototransduction by free opsin. Activation to a similar degree is known not to occur in cones, helping explain why VAD selectively affects night vision.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"30"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040146","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":"Adaptive Responses of Accommodation and Vergence Following Exposure to Augmented Reality in a Head-Mounted Display.","authors":"Walter K Yego, Stuart J Gilson, Rigmor C Baraas, Ellen Svarverud","doi":"10.1167/iovs.66.12.1","DOIUrl":"10.1167/iovs.66.12.1","url":null,"abstract":"<p><strong>Purpose: </strong>The vergence-accommodation conflict in augmented reality head-mounted displays (AR-HMDs) can alter the oculomotor system, leading to visual discomfort and fatigue. The purpose of this work was to evaluate changes of accommodation and vergence and their interaction after completing a visually and cognitively demanding 3D task using an AR-HMD.</p><p><strong>Methods: </strong>Oculomotor parameters, including tonic accommodation (TA), CA/C ratio, tonic vergence (TV), and AC/A ratio were assessed with a photorefractor in 16 participants (10 females; mean age, 23.0 ± 2.6 years). Measurements were taken before and after performing physical and AR versions of an executive function 3D task (Tower of London). Participants moved spheres between pegs at 0.4 m to match the configuration presented on a 2D monitor at 4 m, creating vergence and accommodation demands of 2.5 and 0.25 MA/D. Accommodation demand of virtual content in the AR-HMD, however, remained fixed at 0.5 D.</p><p><strong>Results: </strong>Oculomotor parameters differed across tasks for TA, F(2, 81) = 9.640, P < 0.001, and CA/C ratio, F(2, 84) = 9.720, P < 0.001, but not for TV, F(1, 81) = 0.485, P = 0.488, and AC/A ratio, F(2, 90) = 0.001, P = 0.99. TA and CA/C ratio reduced significantly post-AR task (P < 0.01) but not post-physical task (P > 0.05).</p><p><strong>Conclusions: </strong>The AR task induced changes in the CA/C ratio and TA, but no such changes were observed after the physical task, suggesting that exposure to visually and cognitively demanding 3D tasks in an AR-HMD can, at least temporarily, alter the oculomotor system.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"1"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953988","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":"Kaempferol Alleviates Dry Eye Disease Via Modulation of the IDH3B/CCAR2/IKBKB Axis.","authors":"Shuyan Zhang, Yongyi Sha, Yun Xie, Jiaxu Hong","doi":"10.1167/iovs.66.12.50","DOIUrl":"10.1167/iovs.66.12.50","url":null,"abstract":"<p><strong>Purpose: </strong>Dry eye disease (DED), a multifactorial ocular surface disorder characterized by tear film instability and hyperosmolarity, significantly compromises patients' quality of life. This study evaluates the therapeutic efficacy of kaempferol (KAE), a bioactive flavonoid with demonstrated antioxidant and anti-inflammatory properties and explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>Tear samples were collected from dry eye patients and normal controls for proteomic analysis. Molecular docking was conducted to detect the binding energy of KAE with target proteins. Then, benzalkonium chloride-induced DED mice models were used to evaluate the therapeutic efficacy of KAE in restoring tear film homeostasis and reducing ocular surface damage through hematoxylin & eosin and periodic acid-Schiff staining. Additionally, TUNEL staining was used to assess cornea apoptosis. Cell Counting Kit-8 was used to calculate cell viability of human corneal epithelial-transformed (HCE-T) cells. Comprehensive analyses, including enzyme-linked immunosorbent assays, immunofluorescence, Western blotting, real-time PCR were used to assess cytokine levels, protein and mRNA expression, respectively.</p><p><strong>Results: </strong>By integrating critical biological function analyses with key clinical phenotypes, we identified seven core genes, where IDH3B, CCAR2, and IKBKB exhibited the highest binding affinities with KAE. Moreover, KAE effectively improved tear secretion, tear film stability, and conjunctival goblet cell density while attenuating ocular inflammation and apoptosis in DED mice. Concurrently, treatment with KAE resulted in the upregulation of IDH3B and CCAR2, along with a corresponding downregulation of IKBKB in corneal tissues of DED mice and HCE-T cells.</p><p><strong>Conclusions: </strong>This study provides new insights into the therapeutic potential of KAE as a promising candidate for DED treatment, particularly regulating cell cycle and apoptosis via the IDH3B/CCAR2/IKBKB axis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"50"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113017","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":"Evaluating the Optic Nerve Crush Model to Understand the Function of Microglia in Glaucoma Neuroprotection.","authors":"Xiaowu Gu, Tom Truong, Tiffany Heaster-Ford, Tae-Hoon Kim, Gyeong Jin Kang, Joanna Yung, Miriam Baca, Shawnta Y Chaney, Jeffrey W Hofmann, Jeffrey Eastham, Marion Jeanne","doi":"10.1167/iovs.66.12.56","DOIUrl":"10.1167/iovs.66.12.56","url":null,"abstract":"<p><strong>Purpose: </strong>Microgliosis is a key neuroinflammatory feature in human glaucomatous retinas, believed to contribute to disease progression. This study aims to characterize changes in microglia and intra-retinal axons following optic nerve crush (ONC) and investigate microglial involvement in retinal ganglion cell (RGC) and axonal degeneration.</p><p><strong>Methods: </strong>Using the CD11c.YFP.Venus.Tg mouse line, we tracked microglial activation and assessed the spatiotemporal changes in TUJ1+ intraretinal axons over a 2-week period post-ONC. Microglial function was examined by depleting microglia with the CSF1R inhibitor PLX5622 and using Trem2-deficient mice with dampened microglial activation.</p><p><strong>Results: </strong>Activated microglia accumulated significantly in the retina from day 4 post-ONC, peaking at day 7. Retinal microglia became hypertrophic by day 1 and started proliferating. Axon beading occurred primarily in the peripheral retina by day 2 post-ONC, with more beaded axons appearing along long axonal bundles toward the optic nerve head (ONH) by day 7 and day 14. There was a significant reduction in overall TUJ1 expression and axonal bundle thickness during this period. Despite complete microglial depletion and significantly reduced activation, no differences were observed in the RGC count or the extent of optic nerve damage following ONC.</p><p><strong>Conclusions: </strong>Microglial activation is secondary to axonal injury and plays a bystander role in the ONC model. Robust RGC and axonal degeneration appear unaffected by activated microglia. This finding challenges the utility of the ONC model for evaluating microglia-based glaucoma treatments. Additionally, the study reaffirms the value of combining fluorescent reporter mouse lines with noninvasive ocular imaging for streamlining future research.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"56"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130767","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":"Topical Application of Everolimus Attenuates Lens-Induced Myopia Through mTORC1 Suppression.","authors":"Ruiheng Zhang, Chuyao Yu, Yitong Li, Jiaoyue Dong, Haotian Wu, Yuhang Yang, Xuhan Shi, Wenda Zhou, Hanqing Zhao, Bingyu Cai, Shanshan Wang, Li Dong, Lei Shao, Wei Li, Jost B Jonas, Wenbin Wei","doi":"10.1167/iovs.66.12.55","DOIUrl":"10.1167/iovs.66.12.55","url":null,"abstract":"<p><strong>Purpose: </strong>The mechanistic target of rapamycin complex 1 (mTORC1) signaling has been reported to regulate lens-induced myopia (LIM) in guinea pigs. To address the challenge of delivering lipophilic mTORC1 inhibitors to the posterior eye segment, we developed a novel topical ophthalmic formulation of everolimus, a second-generation rapamycin derivative available only orally, and evaluated its antimyopic efficacy, ocular pharmacokinetics, and safety.</p><p><strong>Methods: </strong>Vehicle formulations were optimized for delivering everolimus to the RPE-choroid complex. The efficacy of different concentrations of everolimus eye drops was tested in 3-week-old male pigmented guinea pigs that underwent LIM. We examined mTORC1 signaling activation, axial elongation, refractive changes, and fundus morphology. Pharmacokinetics was assessed in guinea pigs and New Zealand white rabbits. Ocular safety was evaluated through slit-lamp and fundus examinations, intraocular pressure measurements, and histologic analysis.</p><p><strong>Results: </strong>The optimized formulation of everolimus eye drops (0.001%, 0.01%, and 0.1% w/v) significantly attenuated axial elongation by 0.10 ± 0.03 mm (P = 0.054), 0.11 ± 0.02 mm (P = 0.001), and 0.14 ± 0.03 mm (P = 0.001), respectively. The everolimus eye drops also attenuated fundus tessellation, choroidal thinning, and mTORC1 activation. Peak everolimus concentrations in the RPE-choroid complex of guinea pigs ranged from 5.6 to 103 ng/g, with a Tmax of 1 hour. In rabbits, 0.005% to 0.01% everolimus eye drops achieved concentrations in the RPE-choroid complex comparable to the therapeutic levels in guinea pigs. No corneal, lenticular, retinal toxicity, or intraocular pressure alterations were observed.</p><p><strong>Conclusions: </strong>This novel ophthalmic formulation effectively delivered everolimus to the posterior segment and inhibited myopia progression, supporting its clinical potential for myopia control.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"55"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130930","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":"RPE65 Variant p.(E519K) Causes a Novel Dominant Adult-Onset Maculopathy in 83 Affected Individuals.","authors":"Eline Van Vooren, Filip Van Den Broeck, Quinten Mahieu, Eline Geens, Mattias Van Heetvelde, Marieke De Bruyne, Stijn Van de Sompele, Sheetal Uppal, Eugenia Poliakov, Claire-Marie Dhaenens, Cheryl Y Gregory-Evans, Lies Hoefsloot, Adriana Iglesias Gonzalez, Susanne Kohl, Theresia Zuleger, Tanguy Demaret, Sari Tuupanen, Joke Ruys, Luc Van Os, Elise Platteau, Julie Jacob, Sascha Vermeer, Laurence Postelmans, Karin Dahan, Isabelle Maystadt, Florence Rasquin, Alberta A H J Thiadens, Kirk A J Stephenson, Narin Sheri, Vasily Smirnov, Ian M MacDonald, Kevin Gregory-Evans, T Michael Redmond, Julie De Zaeytijd, Bart P Leroy, Miriam Bauwens, Elfride De Baere","doi":"10.1167/iovs.66.12.53","DOIUrl":"10.1167/iovs.66.12.53","url":null,"abstract":"<p><strong>Purpose: </strong>Recessive RPE65-associated retinopathy is a well-known target for gene therapy, whereas dominant RPE65-associated retinopathy, due to the Irish founder variant p.(D477G), has been reported only once until now and is very rare. Here, we present the discovery of a novel, second dominant RPE65-associated retinopathy caused by variant c.1555G>A, p.(E519K).</p><p><strong>Methods: </strong>Genomic data was investigated in a Belgian discovery cohort (n = 2873) and an international replication cohort (n = 18,796) with inherited retinal disease (IRD). Heterozygous p.(E519K) individuals underwent extensive phenotyping. Haplotype phasing was based on long-read sequencing and microsatellite analysis. Variant p.(E519K) was assessed in vitro using an enzymatic assay, Western blotting, co-immunoprecipitation, cellular thermal shift assay (CETSA), minigene assays, and in silico using protein modeling (AlphaFold).</p><p><strong>Results: </strong>The monoallelic p.(E519K) variant was found in 83 affected individuals from Belgium, the Netherlands, France, and Canada, all of European ancestry. A shared region of 464 kilobases (kb) confirmed a founder effect. Variant p.(E519K) lowers RPE65 protein expression and enzymatic activity, with altered protein stability predicted and experimentally confirmed. Genotype-phenotype data support dominant inheritance and phenotypic variability, respectively, characterized by late-onset macular dystrophy with two main subtypes.</p><p><strong>Conclusions: </strong>The discovery of a dominant RPE65-IRD due to founder variant p.(E519K) reduces the diagnostic gap in dominant IRD and highlights a novel target for therapy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"53"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124759","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":"Pigmentation Pattern of Iris and Fundus in 75 Chinese Families With GPR143-Associated Ocular Albinism.","authors":"Shuowei Chen, Zhen Yi, Yuxi Zheng, Yi Jiang, Dongwei Guo, Xiaoyun Jia, Shiqiang Li, Xueshan Xiao, Qingjiong Zhang, Wenmin Sun","doi":"10.1167/iovs.66.12.69","DOIUrl":"10.1167/iovs.66.12.69","url":null,"abstract":"<p><strong>Purpose: </strong>Ocular albinism is an X-linked recessive genetic disorder that exhibits highly heterogeneous phenotypes involving significant visual deficits and pigmental changes in the eye due to GPR143 variants. The aim of this study is to describe the phenotypic spectra of patients with ocular albinism based on the identification of GRP143 variants in a large Chinese cohort.</p><p><strong>Methods: </strong>GPR143 variants were selected from an in-house data set. Potential pathogenic variants were evaluated using multiple bioinformatic analyses and validated by Sanger sequencing. Clinical data of individuals with likely pathogenic variants in GPR143 were thoroughly analyzed.</p><p><strong>Results: </strong>Forty-six hemizygous variants (18 missense, 8 stop-gain, 8 splicing, 5 frameshift, 6 deletion, and 1 in-frame insertion), including 31 novel ones, were detected in 75 probands with ocular albinism. Three distinct patterns of iris pigmentation and three grades of fundus pigmentation were classified according to available data of the 75 families. Pattern II of iris, characterized by hyperpigmentation in the peripupillary area, was the most prevalent, with involvement of 41.2% of patients. Approximately 52.1% of patients exhibited atypical pigment changes in both the iris and the fundus. Patients with grade 3 fundus, characterized by pronounced depigmentation in the macular region, exhibited significantly poorer best-corrected visual acuity compared to those with other grades (P = 0.0031). Follow-up examinations indicated that fundus pigment deposition increased with age during early childhood.</p><p><strong>Conclusions: </strong>This study expands the variant spectrum of GPR143 and clarifies phenotypic features of ocular albinism, facilitating diagnosis. Hyperpigmentation in the peripupillary area suggests a complex role of GPR143 in melanosome production.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"69"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199279","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}