Molecular Vision最新文献

{"title":"Subretinal delivery of AAV5-mediated human <i>Pde6b</i> gene ameliorates the disease phenotype in a rat model of retinitis pigmentosa.","authors":"Hee Jong Kim, Ji Hoon Kwak, Jun Sub Choi, Jin Kim, Seo Yun Moon, Steven Hyun Seung Lee, Heuiran Lee, Keerang Park, Joo Yong Lee, So-Yoon Won","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>A genetic disorder that affects the beta subunit of cyclic guanosine monophosphate-phosphodiesterase type 6 (PDE6B) in humans leads to autosomal recessive retinitis pigmentosa (RP). This condition causes severe vision loss in early life due to fast deterioration of photoreceptors. This study evaluated the therapeutic potential of subretinal delivery of the adeno-associated virus (AAV)5-mediated human <i>Pde6b</i> gene in an RP rat model caused by <i>Pde6b</i> gene knockout (KO).</p><p><strong>Methods: </strong>We compared the transduction efficiency and tropism of different AAV serotypes (2, 5 and 8) in <i>Pde6b</i> KO rats and found that AAV5 had the highest and most specific expression in photoreceptors. We injected AAV5-<i>Pde6b</i> into the subretinal space of <i>Pde6b</i> KO rats on postnatal day 21. We assessed the protective effects six weeks postinjection by measuring PDE6B protein expression, photoreceptor structure, retinal morphology and thickness, retinal pigment epithelium integrity and visual function.</p><p><strong>Results: </strong>AAV5-<i>Pde6b</i> treatment ameliorated the disease phenotype in <i>Pde6b</i> KO rats by restoring PDE6B protein expression, preserving photoreceptor structure, improving retinal morphology and thickness, and maintaining retinal pigment epithelium integrity. Functional analysis of vision by scotopic electroretinogram (ERG) and optokinetic nystagmus revealed that AAV5-<i>Pde6b</i> treatment significantly improved the visual function of <i>Pde6b</i> gene KO rats compared with AAV5-<i>GFP</i>-injected <i>Pde6b</i> KO rats.</p><p><strong>Conclusions: </strong>Our results demonstrate that AAV5-<i>Pde6b</i> may be a potential therapeutic gene candidate for RP caused by <i>Pde6b</i> mutations.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"127-141"},"PeriodicalIF":1.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multikinase inhibition-mediated proliferative vitreoretinopathy therapy by nanoparticles in rabbits.","authors":"Elif Arslan, Faruk Ozturk, Burcu Uner, Serkan Tureli, Sevda Fatma Muftuoglu, Cetin Tas","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the efficacy of nanoparticles in treating proliferative vitreoretinopathy (PVR) through clinical observation, histology, and immunohistochemistry, despite unsatisfactory surgical outcomes and failed therapies for the current PVR treatment.</p><p><strong>Design: </strong>Twelve rabbits were divided into control and nintedanib (NTB) groups. The rabbits underwent weekly ophthalmologic examinations over a period of four weeks.</p><p><strong>Methods: </strong>At the end of the fourth week, the rabbits' eyes were removed for histological and immunohistochemical evaluation. Three additional rabbits outside the PVR model were administered a 0.5% NTB-loaded liposomal formulation in one eye. The drug concentrations in the vitreous samples were determined using high-pressure liquid chromatography on days 1, 7, 14, and 35.</p><p><strong>Results: </strong>The PVR stages were low in the NTB group, and there was no significant difference between the NTB and control groups (p = 0.108). However, it is worth noting that the group treated with NTB had significantly fewer epiretinal membrane formations during the histological evaluation. In addition, the corrected fluorescence intensity measurement of the subjects for collagen-1 in the NTB group was significantly lower than that in the control group (p = 0.004). Most importantly, no significant adverse effects were observed.</p><p><strong>Conclusions: </strong>Our study has provided preclinical support for a liposomal formulation containing NTB that, with single-dose administration, has the potential to be effective in vivo in preventing the development of PVR and its correlated pathologies without causing any significant side effects.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"142-157"},"PeriodicalIF":1.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragaloside IV improves the survival rates of retinal ganglion cells in traumatic optic neuropathy by regulating autophagy mediated by the AMPK-MTOR-ULK signaling pathway.","authors":"Wu Sun, Guojun Chao, Qiong Wu, Yanting Xia, Mengqiu Shang, Qiping Wei, Jian Zhou, Liang Liao","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Autophagy is involved in the pathological changes of traumatic optic neuropathy (TON), and the regulation of autophagy mediated by the AMPK-mTOR-ULK pathway is a potential therapeutic approach. Astragaloside IV (AS-IV) can regulate autophagy and play a therapeutic role in various diseases. This study aimed to observe the therapeutic effect of astragaloside on TON and the role of AMPK-MTOR-ULK pathway-mediated autophagy in this process.</p><p><strong>Methods: </strong>After the TON model was established, varying doses of AS-IV were administered as an intervention. Additionally, compound C (an AMPK inhibitor) or 3-methyladenine (an autophagy inhibitor) was administered intraperitoneally in conjunction with AS-IV. Samples were collected following a 7-day intervention period. Western blot analysis was conducted to measure the protein and phosphorylation levels of AMPK, mTOR, and ULK proteins. Moreover, western blot and quantitative reverse transcription PCR assays were used to quantify LC3 levels in retinal tissue. LC3 immunofluorescence was performed to examine autophagy levels in the ganglion cell layer (GCL), while transmission electron microscopy was employed to observe autophagosomes. Additionally, BRN3A immunofluorescence was used to label retinal ganglion cells (RGCs) in the GCL, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was used to assess apoptosis within the GCL. Finally, optic nerve conduction function was evaluated using flash visual evoked potentials.</p><p><strong>Results: </strong>After 7 days, the phosphorylation levels of AMPK, mTOR, and ULK proteins in retinal tissue exhibited significant changes following TON. AS-IV treatment enhanced LC3 messenger RNA and protein levels in TON model rats, and the autophagy-promoting effect of AS-IV was reversed by 3-methyladenine. Moreover, AS-IV elevated P-AMPK and P-ULK levels while decreasing P-mTOR levels. AS-IV also improved the survival rate of RGCs and reduced the P2 peak latency of flash visual evoked potentials. These effects were attenuated by the AMPK inhibitor compound C. Additionally, AS-IV increased the levels of AKT1 and P-AKT1 while decreasing P-S6RP levels in the retinal tissue of TON model rats.</p><p><strong>Conclusions: </strong>AS-IV can increase the survival rate of RGCs and improve visual function after TON, which may be related to the improvement of autophagy by regulating the AMPK-MTORC1-ULK pathway.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"99-112"},"PeriodicalIF":1.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum pro-brain natriuretic peptide correlates with optical coherence tomography indices in diabetic retinopathy.","authors":"Shivani Chaturvedi, Sandeep Saxena, Apjit Kaur, Pramod Kumar, Shivani Pandey, Abbas Ali Mahdi, Levent Akduman","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Serum pro-brain natriuretic peptide (BNP) is a 108-amino-acid prohormone that inhibits vascular endothelial growth factor (VEGF) secretion, protecting pericytes from cell death and decreasing retinal vascularization. The purpose of this study was to investigate the correlation of serum pro-BNP with optical coherence tomography (OCT) indices in diabetic retinopathy.</p><p><strong>Methods: </strong>This cross-sectional study investigated 96 consecutive subjects aged between 40 and 65 years: controls n = 24, no diabetic retinopathy (NoDR) n = 24, non-proliferative diabetic retinopathy (NPDR) n = 24, and proliferative diabetic retinopathy (PDR) n = 24. Same-day analysis of blood samples for serum pro-BNP levels was performed and spectral-domain OCT (SD-OCT) was used to measure the following OCT indices: OCT angiography (OCTA) superficial vessel density (SVD), deep vessel density (DVD), and foveal avascular zone (FAZ); OCT retinal nerve fiber layer (RNFL); and OCT ganglion cell analysis (GCA).</p><p><strong>Results: </strong>The mean serum pro-BNP levels for the control, NoDR, NPDR, and PDR groups were 14.07 ± 11.51, 27.35 ± 11.81, 280.44 ± 106.13, and 122.33 ± 43.66 pg/ml, respectively. The mean values of the various OCT parameters correlated with serum pro-BNP were OCTA SVD (r = <math><mo>-</mo></math> 0.360), OCTA DVD (r = 0.408), OCTA FAZ (r = 0.475), OCT RNFL (r = <math><mo>-</mo></math> 0.215) and OCT GCA (r = <math><mo>-</mo></math> 0.285; p<0.001).</p><p><strong>Conclusions: </strong>The serum pro-BNP levels were higher in the NPDR group than in the NoDR group and much lower in the PDR group than in the NPDR group, reflecting a lowering of the protective barrier. These results correlated with the changes in various OCT indices.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"114-125"},"PeriodicalIF":1.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methyltransferase 1 regulates epithelial cell functions in corneal and eyelid development.","authors":"Antonius Christianto, Maureen Mongan, Bo Xiao, Qin Wang, Alvaro Puga, Michael L Robinson, Ying Xia","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>DNA methyltransferase 1 (DNMT1) is a crucial enzyme for the development of the retina and lens in the eye, but its roles in the cornea and eyelids are yet to be investigated.</p><p><strong>Methods: </strong>Ocular surface epithelium (OSE)-specific <i>Dnmt1</i> knockout mice, denoted as <i>Dnmt1^ΔOSE</i> , were generated. Prenatal eye tissues were characterized by hematoxylin and eosin staining; DNMT1 expression, DNA methylation, epithelial differentiation and cell-cell junctions were determined by immunohistochemistry; proliferation was assessed by 5-ethynyl 2´-deoxyuridin labeling and apoptosis evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Keratinocytes derived from <i>Dnmt1^F/F</i> mice were infected with adenoviruses carrying either green fluorescent protein or Cre recombinase to obtain wild-type and <i>Dnmt1-</i>deficient cells. In these cells, <i>Dnmt1</i> expression and epithelial terminal differentiation were evaluated by real-time PCR and/or western blotting; adherence junction and apoptosis were assessed by immunohistochemistry; proliferation was determined by 5-ethynyl 2´-deoxyuridin labeling; transcription factor activities were determined by luciferase reporter assays.</p><p><strong>Results: </strong>The abundant DNMT1 expression and cytosine methylation (5meC) detected in the ocular surface epithelia of wild-type embryos were largely diminished in that of <i>Dnmt1^ΔOSE</i> embryos. Besides lens degeneration, the <i>Dnmt1^ΔOSE</i> fetuses had severe abnormalities of the cornea and eyelids. The surface epithelial cells and stromal keratocytes in the knockout corneas were distorted and the eyelids failed to fuse in the knockout embryos, resulting in an eye-open-at-birth phenotype. At the cellular level, DNMT1-deficient OSE had normal proliferation but increased apoptosis and aberrant cell junctions. In addition, the knockout corneal epithelia failed to express corneal-specific keratin 12, and the knockout eyelid epithelia had increased expression of keratin 10, indicating accelerated terminal differentiation. In vitro studies validated that DNMT1 was required for epithelial cell survival, terminal differentiation and cell junctions, and further identified signaling pathways aberrantly activated by its ablation.</p><p><strong>Conclusion: </strong>DNMT1 maintains survival and differentiation of corneal and eyelid epithelium for the development of the eye.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"85-97"},"PeriodicalIF":1.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Syndromic forms of inherited retinal dystrophies: a comprehensive molecular diagnosis of consanguineous Pakistani families using capture panel sequencing.","authors":"Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.</p><p><strong>Methods: </strong>We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants was assessed using American College of Medical Genetics and Genomics guidelines, followed by Sanger sequencing for segregation analysis.</p><p><strong>Results: </strong>Causative variants in previously reported syndromic IRDs genes were detected in 13/72 (18%) IRD families, including 5/72 (6.94%), 4/72 (5.55%), 2/72 (2.8%), 1/72(1.38%) and 1/72 (1.38%) in Usher syndrome, Bardet-Biedl syndrome, Batten disease, retinitis pigmentosa with situs inversus and Stickler syndrome segregated families, respectively. Disease-causing variants included nine previously reported and six novel homozygous variants, i.e., c.1143G>C in <i>USH2A</i>, c.470G>A in <i>MYO7A</i>, c.877-2A>G in <i>PCDH15</i>, c.347C>T in <i>ARL6</i>, c.581C>T in <i>CLN5</i> and c.100+1G>T in <i>ARL2BP</i> gene segregation with disease phenotype in eight families. Two heterozygous variants of the <i>USH2A</i> gene, i.e., c.12093C>A and c.9815C>T, were segregated in a compound heterozygous form in family RP243. Furthermore, RP151 showed segregation of a heterozygous variant c.247G>A in a Stickler syndrome gene, i.e., <i>COL2A1</i>, in an autosomal dominant manner.</p><p><strong>Conclusions: </strong>This study reaffirms the clinical and genetic heterogeneity of syndromic IRD-associated genes and confirms the usefulness of molecular methods in advancing our understanding of these conditions in consanguineous populations. The most commonly mutated Bardet-Biedl syndrome gene was <i>ARL6</i> (75%) and the most commonly mutated Usher syndrome genes were <i>USH2A</i> (40%) and <i>MYO7A</i> (40%). Our data could serve as a reference for future studies and the development of treatment modalities for affected families of Pakistani origin.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"69-83"},"PeriodicalIF":1.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>LTBP2</i> variants in childhood glaucoma: Phenotypic expansion and clinical experience.","authors":"Anshuman Verma, Arif O Khan, Venkatesh Pochaboina, Sirisha Senthil","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>This study describes a distinct spectrum of latent transforming growth factor-β-binding protein 2 (<i>LTBP2</i>)-related ocular phenotypes in pediatric glaucoma with supporting genetic evidence and highlights our clinical experiences in its management.</p><p><strong>Methods: </strong>A total of 189 children with childhood glaucoma underwent whole-exome sequencing-based genetic testing. Of these, 24 children displayed <i>LTBP2</i>-related phenotypes, among whom 18 cases who tested positive for <i>LTBP2</i> variants were included in the study. The identified variants were confirmed through Sanger sequencing whenever possible and analyzed using in silico tools. The clinical presentation, genetic variants, and management of these 18 cases were thoroughly reviewed and presented.</p><p><strong>Results: </strong>All 36 eyes of the 18 children with biallelic <i>LTBP2</i> variants exhibited megalocornea without Descemet break, iridodonesis, and ectopia lentis. Pupillary changes were noted in all eyes, with persistent pupillary membrane in 78% (28/36) and ectropion uveae in 19% (7/36) eyes. Secondary glaucoma was observed in 72% (26/36) eyes, requiring surgery in 13 of these. Retinal pathology was noted in 47% (17/36) eyes. Lensectomy was performed in 94% (34/36) eyes with a mean age of 4.09 ± 3.5 years. Logistic regression analysis suggested that older age at lensectomy increased the risk of secondary glaucoma (hazard ratio, 1.69; [95% Confidence Interval: 1.00, 2.86], <i>p</i> < 0.05). The identified <i>LTBP2</i> variants included five stop-gain variations, six frameshift variations, and one substitution variation, with five being novel and seven classified as rare variants.</p><p><strong>Conclusions: </strong>The study expands the classic <i>LTBP2</i>-related phenotype spectrum in an Indian pediatric glaucoma cohort, highlighting additional features such as persistent pupillary membrane, ectropion uveae, and associated retinal pathology. These ocular manifestations were predominantly linked to nonsense <i>LTBP2</i> variants. From a management standpoint, early lensectomy can help prevent secondary glaucoma, while timely identification and treatment of peripheral retinal pathology can reduce the risk of sight-threatening complications.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"55-67"},"PeriodicalIF":1.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics and phenotypes of <i>RPE65</i> mutations in inherited retinal degeneration: A study from a tertiary eye care center in Brazil.","authors":"Sarah Pereira de Freitas Cenachi, Maria Frasson, Virgínia Mares, Rodrigo Rezende Arantes, Anna Luiza Braga Albuquerque, Anna Laura Marques Nascentes, Luiz Armando Cunha De Marco, Márcio Bittar Nehemy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Biallelic variants in the retinal pigment epithelium-specific 65-kDa protein (<i>RPE65</i>) gene are linked to several inherited retinal diseases (IRDs), including Leber congenital amaurosis (LCA), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP). This study screened patients from a tertiary center in Brazil with IRDs for <i>RPE65</i> variants to characterize the associated phenotypes.</p><p><strong>Methods: </strong>LCA, EOSRD, and RP diagnoses were based on predefined clinical criteria. Patients underwent comprehensive clinical evaluations and retinal imaging. Genomic DNA was analyzed using a next-generation sequencing panel for IRDs, covering 238 genes.</p><p><strong>Results: </strong><i>RPE65</i> variants were identified in seven of the 68 patients screened. Of these, three were homozygous, and four were compound heterozygous for the identified mutant alleles. A total of six variants were detected, of which one was novel. The p.Leu341Ser (c.1022T>C) mutation was the most prevalent, being found in four of seven patients. Visual loss onset ranged from birth to the third decade of life. A consistent clinical feature observed in all patients was some degree of pigmentary change upon peripheral retinal examination.</p><p><strong>Conclusions: </strong><i>RPE65</i> variants were found in 10.3% of cases in this series, associated with LCA, EOSRD, and RP. These variants were consistently linked with pigmentary changes in the peripheral retina and exhibited variable manifestations regarding arteriolar attenuation, disc pallor, and macular appearance. In this series, the prevalence of the p.Leu341Ser (c.1022T>C) mutation was 57%.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"45-54"},"PeriodicalIF":1.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of genetic factors underlying severe retinopathy of prematurity in preterm infants.","authors":"Huiqing Sun, Zhiyi Xia, Mingchao Li, Zengyuan Yu, Zhangsheng Wang, Shan Xing, Ping Cheng, Hongbo Zhang, Lifeng Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Retinopathy of prematurity (ROP) is a pathological condition characterized by abnormal proliferation of retinal vessels and it represents the primary cause of visual impairment in preterm infants. There is increasing backing for the involvement of genetic factors in the onset of ROP.</p><p><strong>Methods: </strong>A prospective cohort study assessed the allele frequency and genotype distribution of gene polymorphisms in angiogenesis, inflammation and oxygen-sensing pathways in preterm infants with severe ROP. The role of genetic polymorphism in ROP development was investigated using next-generation sequencing (NGS) combined with candidate genes and data mining methods.</p><p><strong>Results: </strong>A total of 47 confirmed severe ROP cases and gestational age, birthweight and days of oxygen therapy plus 35 similar control infants were enrolled in this study. In the initial hypothesis-generating survey, we selected a p value of 0.01 to minimize false positives while retaining true positives. Using this criterion, we identified 19 single-nucleotide polymorphisms across 11 genes that were associated with the occurrence of ROP (<i>ZNF717</i>, <i>IHH</i>, <i>SEC22B</i>, <i>IGSF3</i>, <i>HYDIN)</i>, <i>GGT1</i>, <i>FRG1</i>, <i>CDC27</i>, <i>LRRC37A3</i>, <i>CTAGE4</i> and <i>ADAMTS7</i>; all p<0.001). Compared with the control group, 62 single-nucleotide polymorphisms in 19 candidate genes (<i>VEGF</i>, <i>EPO, EPAS-1</i>, <i>HIF1A</i>, <i>RUNX1</i>, <i>ESR1</i>, <i>CFH</i>, <i>PDGFB</i>, <i>JAK</i>, <i>STAT</i>, <i>IGF-1</i>, <i>IGFBP2</i>, <i>GPX4</i>, <i>TLR4</i>, <i>ROS1</i>, <i>CYP</i>, <i>TP53BP1</i>, <i>NOS3</i>, <i>TNF</i>) representing angiogenic, inflammation, oxygen-sensing pathways and proliferative retinopathic diseases were found to be associated with the development of severe ROP (all p<0.01).</p><p><strong>Conclusions: </strong>Using NGS gene analysis suggests that genetic risk factors may play an important role in susceptibility to the development of ROP.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"33-43"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subclinical parents assist in the detection of genetic variants in keratoconus by trio-based whole-exome sequencing.","authors":"Xingyong Li, Yinghao Yao, Shilai Xing, Siwen Ma, Shuaiyue Pang, Yang Zhou, Shihao Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the genetic variants of 14 keratoconus trios containing subclinical parents.</p><p><strong>Methods: </strong>Trio-based whole-exome sequencing was performed in 14 keratoconus trios containing subclinical parents. The variants identified in candidate genes of keratoconus were analyzed by multiple bioinformatics tools.</p><p><strong>Results: </strong>We identified 12 variants in 10 candidate genes of keratoconus (<i>COL5A1</i>, <i>TGFBI</i>, <i>CAST</i>, <i>MPDZ</i>, <i>WNT10A</i>, <i>MYOF</i>, <i>ERMP1</i>, <i>MAP3K19</i>, <i>COL1A1</i>, and <i>WNT16</i>). All variants were novel, not previously reported, and defined as uncertain significance according to the American College of Medical Genetics and Genomics guidelines. All variants were heterozygous and autosomal dominant cosegregated in keratoconus families.</p><p><strong>Conclusions: </strong>We found that the candidate variants identified in clinically diagnosed patients and their subclinical parents may cause keratoconus through an autosomal dominant inheritance pattern, with different variable expressivity. This study indicates that genetic testing may play an important role in identifying patients with latent keratoconus and high-risk individuals for corneal ectasia after refractive surgery.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"23-32"},"PeriodicalIF":1.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}