Investigative ophthalmology & visual science最新文献

{"title":"Magnetic Resonance Dacryocystography for Precise Diagnosis of Lacrimal and Perilacrimal Lesions.","authors":"Xuejun Guo, Min Gao, Yulong Qi, Qiao Shi, Qiqiang Li, Mingmei Li, Hongbing Li","doi":"10.1167/iovs.66.3.17","DOIUrl":"10.1167/iovs.66.3.17","url":null,"abstract":"<p><strong>Purpose: </strong>The accurate determination of the etiology and location of lacrimal passage obstruction is key to treatment. However, the main assessments for lacrimal passage are invasive and have limited value. This study aimed to analyze the causes of obstruction of the lacrimal passage and investigate the diagnostic value of magnetic resonance dacryocystography (MRD).</p><p><strong>Methods: </strong>Fifty-six patients (69 eyes) with lacrimal disease underwent MRD after lacrimal irrigation. The stenotic site and degree were determined. The accuracies of the diagnoses of lesions at different sites based on MRD and routine clinical assessment were determined and compared, and a noninferiority test was used to verify the values obtained via MRD.</p><p><strong>Results: </strong>The lesion location determined through lacrimal irrigation was inconsistent with that determined through MRD. The overall accuracy of routine clinical assessment was approximately 79.7% (55 of 69) and that of MRD reached 98.6% (68 of 69). For the lesion location, the clinical misdiagnosis rates were 38.9%, 43.8%, and 63.6% for the lacrimal sac, nasolacrimal duct, and perilacrimal passage, respectively. The MRD and surgical pathology results for the lacrimal sac, nasolacrimal duct, and perilacrimal passage were consistent, except for the lacrimal canaliculus. The P value for the noninferiority of MRD to surgical pathology was 0.32.</p><p><strong>Conclusions: </strong>MRD is noninvasive and has high value for determining the cause, location, and degree of lacrimal stenosis. Its findings are nearly as accurate as those of surgical pathology. MRD should be recommended over other invasive methods for evaluating lacrimal and prelacrimal lesions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"17"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567046","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":"LncRNA ENST00000581911 Regulates Extraocular Muscle Remodeling by Interacting With KHSRP in Thyroid Eye Disease.","authors":"Mingsu Shi, Rongmei Zhou, Weiai Shen, Yu Liang, Yihan Zhang, Lingyun Liu, Runyi Shao, Yanxi Fang, Chen Zhao, Lianqun Wu","doi":"10.1167/iovs.66.3.46","DOIUrl":"10.1167/iovs.66.3.46","url":null,"abstract":"<p><strong>Purpose: </strong>Thyroid eye disease (TED) is a visually debilitating and cosmetically disfiguring orbital disorder, characterized by the remodeling of extraocular muscles (EOMs). This study aimed to investigate the role of long non-coding RNA (lncRNA) ENST00000581911 in the EOMs of TED.</p><p><strong>Methods: </strong>LncRNA microarray analysis was performed on EOM tissues sampled from patients with TED and patients with concomitant esotropia. LncRNA ENST00000581911 was identified and subjected to bioinformatics analysis. High-throughput RNA sequencing, CCK-8 assay, CFSE staining, and ELISA were used to investigate the regulatory function of ENST00000581911 in vitro. Furthermore, RNA pull-down, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and western blot (WB) analyses were applied to identify the RNA-binding protein (RBP) interacting with ENST00000581911.</p><p><strong>Results: </strong>A total of 1261 lncRNAs were found to be differentially expressed in the EOMs of TED, with 648 upregulated and 613 downregulated lncRNAs. Among these, the upregulated lncRNA ENST00000581911 exhibited the highest expression level, as validated by quantitative real-time PCR (qRT-PCR). Functional analysis demonstrated that ENST00000581911 might be involved in inflammatory response, regulation of muscle contraction, and amino sugar and nucleotide sugar metabolism. RNA sequencing of ENST00000581911-overexpressing and control orbital fibroblasts (OFs) showed that ENST00000581911 might play a regulatory role in DNA replication, extracellular matrix, and cell cycle. Furthermore, KHSRP was identified as the RBP of ENST00000581911. Overexpression of ENST00000581911 promoted cell proliferation and hyaluronic acid secretion in OFs, whereas silencing KHSRP attenuated these effects.</p><p><strong>Conclusions: </strong>This study provides novel insights into the role of lncRNA ENST00000581911 in the pathogenesis of EOM remodeling in TED. ENST00000581911 may serve as a potential therapeutic target of TED.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"46"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673882","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":"EFEMP1-Mediated Regulation of Choroidal Vascular Dysfunction in Myopia: Insights Into the FOXO3/VEGFA Pathway as a Therapeutic Target.","authors":"Wen-Qing Shi, Bing Li, Yuting Shao, Wenting Han, Yule Xu, Qing Jiang, Shen Qu, Xiaodong Zhou, Yanlong Bi","doi":"10.1167/iovs.66.3.43","DOIUrl":"10.1167/iovs.66.3.43","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the role of EFEMP1 in choroidal vascular dysfunction and its implications for myopia progression, specifically focusing on the FOXO3/VEGFA signaling pathway as a potential therapeutic target.</p><p><strong>Methods: </strong>We utilized adeno-associated virus (AAV) to overexpress and knock down EFEMP1 in the choroid of guinea pigs. Subsequent proteomic analyses were conducted on the choroidal tissue. We used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify relevant pathways and genes. In vitro experiments were performed on RF/6A cells, where both EFEMP1 and FOXO3 underwent overexpression and knockdown. We conducted a series of cell culture experiments, including assessments of cell proliferation, migration, tube formation, and choroidal sprouting assays, to evaluate the functional effects of EFEMP1. Quantitative reverse transcription PCR and Western blot analyses were utilized to measure gene and protein expression levels.</p><p><strong>Results: </strong>Silencing EFEMP1 significantly reduced choroidal vascular dysfunction and slowed the progression of myopia. Proteomic analysis demonstrated that EFEMP1 regulates FOXO3 activity, resulting in increased VEGFA expression in RF/6A cells and promoting angiogenesis. Conversely, knockdown of FOXO3 led to decreased VEGFA levels, confirming that EFEMP1 modulates VEGFA expression through FOXO3.</p><p><strong>Conclusions: </strong>Targeting EFEMP1 may offer a novel therapeutic strategy for the prevention and treatment of myopia by alleviating associated vascular dysregulation. Further exploration of the FOXO3/VEGFA pathway could provide additional insights into therapeutic interventions for myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663361","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":"Reversal of Diabetic Dry Eye by Topical Opioid Receptor Blockade Follows Dual Pathways.","authors":"David Diaz, Joseph W Sassani, Ian S Zagon, Patricia J McLaughlin","doi":"10.1167/iovs.66.3.24","DOIUrl":"10.1167/iovs.66.3.24","url":null,"abstract":"<p><strong>Purpose: </strong>To determine pathways in the trigeminal ganglion and corneal epithelium that are targeted by topical naltrexone (NTX) treatment for dry eye.</p><p><strong>Methods: </strong>NTX drops were administered topically daily for 15 days to the corneal surface of male and female adult type 1 diabetic rats. Schirmer scores and corneal sensitivity were measured at baseline, 5, 10, and 15 days. Trigeminal ganglion and corneal epithelium were processed for immunohistochemistry to detect expression of opioid growth factor receptor (OGFr), Ki67, nerve growth factor, insulin-like growth factor-1, calcitonin gene-related peptide, substance P, and TNF-α. A proteomic study determined protein changes in the cornea.</p><p><strong>Results: </strong>Corneal sensitivity and tear production in diabetic rats were restored to normal levels within 5 days after topical NTX. Assessment of corneal tissue after 15 days of treatment revealed that defects in OGFr expression, epithelial cell number, and Ki67+ expression were restored to normal by NTX. Inflammation markers (e.g., TNF-α) were reduced in tissue from diabetic rats treated with NTX. Proteomic data suggest diabetes causes dysregulation in inflammatory biological processes. The percentages of calcitonin gene-related peptide-positive neurons, but not substance P-positive neurons, in the trigeminal ganglion were increased after NTX treatment. Diabetic male and female rats responded to NTX in a comparable manner.</p><p><strong>Conclusions: </strong>Type 1 diabetes results in decreased tear production and altered corneal surface sensitivity. These complications coincide with dysregulated OGFr that maintains ocular homeostasis. Reversal of dry eye and restoration of corneal sensitivity in diabetic male and female rats after 15 days of topical treatment with NTX occur following dual pathways of increased cellular proliferation and reduction of inflammation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"24"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585697","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":"Dicer Loss in Müller Glia Leads to a Defined Sequence of Pathological Events Beginning With Cone Dysfunction.","authors":"Daniel Larbi, Alexander M Rief, Seoyoung Kang, Shaoheng Chen, Khulan Batsuuri, Sabine Fuhrmann, Suresh Viswanathan, Stefanie G Wohl","doi":"10.1167/iovs.66.3.7","DOIUrl":"10.1167/iovs.66.3.7","url":null,"abstract":"<p><strong>Purpose: </strong>The loss of Dicer in Müller glia (MG) results in severe photoreceptor degeneration, as it occurs in retinitis pigmentosa or age-related macular degeneration; however, the sequence of events leading to this severe degenerative state is unknown. The aim of this study was to conduct a chronological functional and structural characterization of the pathological events in MG-specific Dicer-conditional knockout (cKO) mice in vivo and histologically.</p><p><strong>Methods: </strong>To delete Dicer and mature microRNAs (miRNAs) in MG, two conditional Dicer1 knockout mouse strains (Rlbp-CreER:tdTomato:Dicer-cKOMG and Glast-CreER:tdTomato:Dicer-cKOMG) were created. Optical coherence tomography (OCT), electroretinograms (ERGs), and histological analyses were conducted to investigate structural and functional changes up to 6 months after Dicer deletion.</p><p><strong>Results: </strong>Dicer/miRNA loss in MG leads to (1) impairments of the area spanning from the external limiting membrane (ELM) to the retinal pigment epithelium (RPE), (2) cone photoreceptor dysfunction, and (3) retinal remodeling and functional loss of the inner retina at 1, 3, and 6 months after Dicer loss, respectively, in both of the knockout mouse strains. Furthermore, in the Rlbp-CreER:tdTomato:Dicer-cKOMG strain, rod photoreceptor impairment was found 4 months after Dicer depletion (4) accompanied by alteration of RPE integrity (5).</p><p><strong>Conclusions: </strong>MG Dicer loss in the adult mouse retina impacts cone function prior to any measurable changes in rod function, suggesting a pivotal role for MG Dicer and miRNAs in supporting cone health. A partially impaired RPE, however, seems to accelerate rod degeneration and overall degenerative events.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541497","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 TCF4 Gene Regulates Apoptosis of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy.","authors":"Tatsuya Nakagawa, Tetsuro Honda, Taichi Yuasa, Go Nishiuchi, Masakazu Sato, Ayumi Tokunaga, Makiko Nakahara, Theofilos Tourtas, Ursula Schlötzer-Schrehardt, Friedrich Kruse, Prema Padmanabhan, Amit Chatterjee, Gajanan Sathe, Vivek Ghose, Narayanan Janakiraman, Derek J Blake, Noriko Koizumi, Sailaja Elchuri, Naoki Okumura","doi":"10.1167/iovs.66.3.16","DOIUrl":"10.1167/iovs.66.3.16","url":null,"abstract":"<p><strong>Purpose: </strong>Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disorder characterized by excessive extracellular matrix (ECM) accumulation and corneal endothelial cell death. CTG trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene represents the most significant genetic risk factor. This study aimed to elucidate the role of TCF4 in FECD pathogenesis through comprehensive proteomic analysis.</p><p><strong>Methods: </strong>Corneal endothelial cells isolated from patients with FECD harboring TCF4 trinucleotide repeat expansion were immortalized to establish an FECD cell model (iFECD). CRISPR/Cas9-mediated genome editing was employed to generate TCF4-knockout iFECD cells. Whole-cell proteome analysis was performed using liquid chromatography-mass spectrometry, followed by pathway enrichment analysis of differentially expressed proteins (DEPs). The effects of TCF4 deletion on TGF-β-mediated protein aggregation and cell death were evaluated using Western blot analysis, flow cytometry, and aggresome detection assays.</p><p><strong>Results: </strong>Proteomic analysis identified 88 DEPs among 6510 detected proteins. Pathway analysis revealed significant enrichment in ECM-associated pathways, oxidative stress responses, and cellular motility. TCF4 deletion attenuated TGF-β-induced cell death in iFECD cells. Concordantly, Western blot analysis demonstrated that TCF4 deletion suppressed TGF-β2-mediated cleavage of caspase-3 and poly (ADP-ribose) polymerase. Flow cytometric analysis of Annexin V-positive cells confirmed reduced apoptosis in TCF4-deleted cells following TGF-β2 treatment. Additionally, aggresome detection assays revealed that TCF4 deletion diminished TGF-β2-induced protein aggregation.</p><p><strong>Conclusions: </strong>This study demonstrates a crucial role for TCF4 in FECD pathogenesis, particularly in ECM regulation and protein aggregation-induced cell death.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567142","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":"Pten Loss Triggers Progressive Photoreceptor Degeneration in an mTORC1-Independent Manner.","authors":"Joseph Hanna, Yacine Touahri, Alissa Pak, Luke Ajay David, Edwin van Oosten, Rajiv Dixit, Laura M Vecchio, Dhruv Nimesh Mehta, Ren Minamisono, Isabelle Aubert, Carol Schuurmans","doi":"10.1167/iovs.66.3.45","DOIUrl":"10.1167/iovs.66.3.45","url":null,"abstract":"<p><strong>Purpose: </strong>Silencing Phosphatase and tensin homolog (Pten) is a proposed therapeutic strategy for tissue regeneration to treat neurological disorders. However, Pten is pleiotropic, inhibiting several signaling and metabolic pathways, including mTORC1 and glycolysis, both pro-regenerative in certain contexts. This study aims to assess the long-term impact of inactivating Pten on photoreceptor survival in the retina and to identify downstream pathway(s).</p><p><strong>Methods: </strong>We assessed retinal integrity in Pten conditional knock-outs (cKOs) that were retinal progenitor cell (RPC)-specific (Pten RPC-cKO), a congenital model, or rod-specific (Pten Rho-cKO). We examined early changes in photoreceptor gene expression and used immunostaining to assess photoreceptors, reactive astrocytes, microglia, angiogenesis, and subretinal deposit formation from postnatal day (P) 21 to 1 year of age. Pten RPC-cKO retinal explants were treated with rapamycin, an mTOR inhibitor, or 2-deoxy-D-glucose (2DG), a glycolysis inhibitor.</p><p><strong>Results: </strong>In both Pten-cKO models, retinas display signs of early pathogenesis as photoreceptor-specific gene expression is downregulated at P0, before photoreceptor loss. Pten loss triggers progressive rod and cone degeneration beginning at P21 in Pten RPC-cKOs and at 6 months of age in Pten Rho-cKOs. Activated microglia and astrocytes, and increased angiogenesis, are observed in both Pten-cKO models, while subretinal amyloid-β deposits develop in Pten RPC-cKOs. Rapamycin accelerates photoreceptor degeneration in Pten RPC-cKOs, whereas 2DG has no effect.</p><p><strong>Conclusions: </strong>Our findings suggest that Pten loss, either in RPCs as a congenital model, or solely in mature rod photoreceptors, leads to progressive retinal degeneration that is exacerbated by mTORC1 suppression, drawing into question the therapeutic value of Pten-mTORC1 manipulations.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"45"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673885","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":"Fibrosis-Related Gene and Protein Expression in Normal and Glaucomatous Trabecular Meshwork Cells.","authors":"Yong-Feng Yang, Paul Holden, Ying Ying Sun, Jennifer A Faralli, Donna M Peters, Kate E Keller","doi":"10.1167/iovs.66.3.48","DOIUrl":"10.1167/iovs.66.3.48","url":null,"abstract":"<p><strong>Purpose: </strong>Glaucomatous trabecular meshwork (GTM) tissue is characterized by excess fibrotic-like extracellular matrices, which negatively impacts aqueous humor outflow. Endothelial-to-mesenchymal transition (EndMT) is the process by which tissues develop fibrosis. In this study, we investigated fibrotic-related gene and protein profiles of non-glaucomatous trabecular meshwork (NTM) and GTM cells.</p><p><strong>Methods: </strong>Primary cells were cultured from NTM (n = 6) and GTM (n = 5) age-matched cadaver eyes. RNA was harvested and mRNA profiling of 750 genes was performed using the human fibrosis panel (NanoString). Quantitative PCR (qPCR), Western blotting, and immunofluorescence microscopy were performed. A matrix metalloproteinase (MMP) fluorogenic assay was used to quantitate enzyme activity.</p><p><strong>Results: </strong>Classic EndMT biomarkers, α-SMA, SNAI2, TWIST1, TWIST2, and VIM, were upregulated in GTM cells, whereas increased phosphorylated SMAD2-3 indicated increased TGFβ signaling. GTM cells had increased deposition of FN-EDA fibronectin fibrils, but reduced amounts of FN-EDB fibrils, and altered immunostaining of active α5β1 and αvβ3 integrins. NanoString analysis showed that 2 genes were upregulated and 28 genes were downregulated in GTM cells compared with NTM cells. Western immunoblotting confirmed increased protein levels of N-cadherin and decreased MMP2, CHI3L1, COL6A3, and SERPINF1 proteins in GTM cells. Whereas MMP2 gene and protein levels were reduced, there was increased MMP activity.</p><p><strong>Conclusions: </strong>Increased expression of α-SMA, FN-EDA, N-cadherin, SNAI2, TWISTs, VIM, TGFβ signaling, and MMP activity are consistent with GTM cells acquiring an EndMT phenotype. In combination with tissue studies, cultured GTM cells are a useful in vitro model for studying the fibrotic process in glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"48"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692136","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":"Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy.","authors":"Rajya L Gurung, Charvi Nangia, Tengda Cai, Liesel M FitzGerald, Bennet J McComish, Ebony Liu, Georgia Kaidonis, Bronwyn Ridge, Alex W Hewitt, Brendan Vote, Nitin Verma, Jamie E Craig, Colin N A Palmer, Kathryn P Burdon, Weihua Meng","doi":"10.1167/iovs.66.3.55","DOIUrl":"10.1167/iovs.66.3.55","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis. The Australian cohort comprised 551 cases of DME and 599 controls recruited from the states of South Australia and Tasmania. The Scottish cohort comprised 1951 cases of diabetic maculopathy and 6541 controls from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS). Genotyping, imputation, and association analysis using logistic regression were conducted in each cohort, before combining summary statistics in a meta-analysis using the GWAMA package.</p><p><strong>Results: </strong>A locus on chromosome 7 reached genome-wide significance in GoDARTS but showed the opposite direction of effect in the Australian cohort. The meta-analysis identified two suggestive associations (P < 5 × 10-6) for diabetic maculopathy risk with similar effect direction; one at chromosome 1 close to the RNU5E-1 gene and one at chromosome 13 upstream of the ERICH6B gene. The two loci were evaluated in silico for potential functional links to diabetic maculopathy. Both are located in regulatory regions and have annotations indicating regulatory functions. They are also expression quantitative trait locus (eQTLs) for genes plausibly involved in diabetic maculopathy pathogenesis, with links to folate metabolism and the regulation of VEGF.</p><p><strong>Conclusions: </strong>The study suggests several promising SNPs and genes related to diabetic maculopathy risk. Despite being the largest genetic study of diabetic maculopathy to date, larger, homogeneous cohorts will be required to identify robust genetic risk loci for the disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"55"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709801","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":"Diversity of Peripheral Refraction Patterns-Have These Been Oversimplified?","authors":"Megha Antony, Rakesh Maldoddi, David A Atchison, Pavan Kumar Verkicharla","doi":"10.1167/iovs.66.3.58","DOIUrl":"10.1167/iovs.66.3.58","url":null,"abstract":"<p><strong>Purpose: </strong>To describe patterns of peripheral refraction based on spherical equivalent refraction and on tangential and sagittal refractions, and to assess the association of peripheral refraction patterns with different central refractions.</p><p><strong>Methods: </strong>Peripheral refraction data from 737 individuals (14.7 ± 5.1 years old) were analyzed. Peripheral refraction was determined along the horizontal field at ±30° eccentricity using an open-field autorefractor in 89 hyperopes, 276 emmetropes, and 372 myopes. Values were converted into spherical equivalent refraction and into tangential and sagittal refractions. Nine different peripheral refraction patterns (A-I) were described based on spherical equivalent refraction, and 81 patterns were described based on tangential and sagittal refractions.</p><p><strong>Results: </strong>Using spherical equivalent refraction, all nine possible peripheral refraction patterns (A-I) were represented. Type I (relative peripheral myopia in nasal and temporal retinas) was seen in 40% of hyperopes, in 32% of emmetropes, and in 8% of myopes. Type A (relative peripheral hyperopia in nasal and temporal retinas) was seen in 20% of myopes and in ≤1% of hyperopes and emmetropes. No pattern was unique to any refractive group. Using tangential and sagittal refractions, 47 out of 81 possible patterns were represented. The three refractive groups shared 19 patterns in common. Hyperopes, emmetropes, and myopes had two, six, and eleven unique patterns, respectively.</p><p><strong>Conclusions: </strong>Many types of peripheral refraction patterns were observed, and these may provide insights into the complexities of eye growth and myopiogenesis. Tangential and sagittal refractions should be considered to understand peripheral refraction rather than spherical equivalent refraction alone.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"58"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719359","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}