Molecular Vision最新文献

{"title":"Analysis of cytogenetic germline changes in Polish patients with retinoblastoma.","authors":"Dorota Wicher, Danuta Sielska-Rotblum, Urszula Zawadzka-Wiech, Monika Kowalczyk-Rusak, Olga Rutynowska-Pronicka, Agnieszka Gietka, Elwira Kulicka, Marlena Mlynek","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Retinoblastoma, the most common eye tumor in children, can occur in hereditary or nonhereditary forms. In the hereditary form, various germline alterations, single nucleotide (SNVs) or copy number variations (CNVs) in the <i>RB1</i> gene can be detected in patients. The aim of this study was to analyze cytogenetic germline changes in Polish patients with retinoblastoma and to assess whether cytogenetic techniques still have their application in diagnostics for retinoblastoma patients in the era of next-generation sequencing (NGS).</p><p><strong>Methods: </strong>The results of genetic testing for germline mutations in patients with retinoblastoma performed between 2013 and 2023 were analyzed. In patients with cytogenetic alterations (CNV group, n = 19), the form of disease, age of onset, the first symptom, family history, and the type and extent of cytogenetic changes were verified. Comparative analyses were conducted between the CNV and SNV (n = 83) groups as well as the group of patients with normal genetic test results (n = 126).</p><p><strong>Results: </strong>Cytogenetic changes were detected in 19 probands. These included: 16 deletions (10 partial and 6 whole gene deletions), 2 duplications, and 1 balanced translocation. Partial gene deletions included from 1 to 16 exons. In the CNV group, bilateral involvement predominated, with strabismus being the most common initial symptom. The mean age of onset was 16.9 months (median = 11 months; IQR, 8-22 months) and was lower in patients with bilateral involvement and partial gene deletions. Statistically significant differences compared to patients with normal genetic test results were observed in terms of laterality, the age of onset, initial symptom, and the family history of retinoblastoma. No such differences were found between the CNV and SNV groups.</p><p><strong>Conclusions: </strong>Cytogenetic changes constitute a significant part of germline alterations in patients with retinoblastoma. Cytogenetic techniques should still be considered in diagnostic protocols, especially in patients with bilateral involvement and/or positive family history, as well as in parents of patients with CNV.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"267-274"},"PeriodicalIF":1.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499402","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":"Bietti crystalline corneoretinal dystrophy: Advances in understanding and gene therapeutic approaches.","authors":"Guangrong Zhao, Dayou Ding","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bietti crystalline dystrophy (BCD), an autosomal recessive inherited retinal disorder caused by mutations in the <i>CYP4V2</i> gene, has long remained therapeutically challenging. Recent advances in adeno-associated virus-based gene therapy have emerged as promising therapeutic strategies for patients with BCD. This review synthesizes current knowledge regarding the molecular genetic mechanisms underlying BCD pathogenesis and examines recent developments in diagnostic approaches and gene therapeutic interventions. We specifically analyze the clinical outcomes of three investigational gene therapy products-ZVS101e, NGGT001, and VGR-R01-focusing on their preliminary efficacy, safety profiles, and tolerability. Key parameters evaluated include dosing strategies, routes of administration, adverse event profiles, and improvements in best-corrected visual acuity. The collective evidence suggests these therapeutic candidates show potential for decelerating disease progression and enhancing visual function. Future optimization of these approaches should carefully consider administration sites and modalities, injection volumes, and disease severity at intervention. With gene replacement therapy for BCD advancing through late-stage clinical development, regulatory approval and clinical implementation may be anticipated in the near future.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"256-265"},"PeriodicalIF":1.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636094","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":"Cysteinyl leukotriene receptor 1 regulates cellular glucose levels in human retinal cells.","authors":"Andreas Koller, Susanne Maria Brunner, Julia Preishuber-Pflügl, Daniela Mayr, Christian Runge, Herbert Anton Reitsamer, Andrea Trost","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Cysteinyl leukotriene receptor 1 (CysLTR1), originally described as a proinflammatory G protein-coupled receptor, has been shown to possess diverse nonimmunological properties. One of these functions is to modulate glucose-stimulated insulin secretion in β cells. Furthermore, the inhibition of CysLTR1 increases retinal cell survival in early diabetic retinopathy. Nevertheless, the potential of CysLTR1 to modulate glucose levels in retinal vascular cells, such as endothelial cells (ECs) and pericytes (PCs), is unknown. Therefore, we determined the intracellular glucose levels in retinal cells in vitro after the inhibition of CysLTR1 under standard and high-glucose culture conditions.</p><p><strong>Methods: </strong>Primary human ECs, PCs, and the ARPE-19 cell line were cultured under standard (5.5 mmol/l glucose + 27.5 mmol/l mannitol) and high-glucose (33.0 mmol/l) conditions in the absence and presence of the specific CysLTR1 antagonists montelukast and zafirlukast for 1, 3, and 7 days. CysLTR1 expression was determined by immunofluorescence microscopy. CysLT secretion was measured by enzyme-linked immunosorbent assay. The effects of high glucose and CysLTR1 inhibition on cell viability and intracellular glucose levels were analyzed by luminescence-based assays. Furthermore, the transendothelial and transepithelial electrical resistance of the ECs and ARPE-19 monolayers was measured.</p><p><strong>Results: </strong>CysLTR1 inhibition under standard glucose culture conditions increased the cellular glucose levels in retinal ECs, PCs, and ARPE-19 cells after 1 and 3 days of treatment. Under high-glucose culture conditions, CysLTR1 inhibition for 1 day reduced the intracellular glucose level in ARPE-19 cells. However, CysLTR1 inhibition for 3 days increased the level of intracellular glucose in ARPE-19 cells under high-glucose culture conditions. Furthermore, CysLTR1 inhibition reduced the tightness of the EC and ARPE-19 monolayers under standard culture conditions but increased the tightness of the ARPE-19 monolayers under high-glucose conditions.</p><p><strong>Conclusions: </strong>CysLTR1 is considered a potential target for the treatment of type 2 diabetes and early diabetic retinopathy. Our data revealed that CysLTR1 activity directly regulates cellular glucose levels in retinal cells, supporting these hypotheses. Interestingly, the effect of CysLTR1 activity on glucose levels was reversed under acute metabolic stress. Thus, the activity of CysLTR1 appears to be more complex in terms of glucose metabolism and needs to be studied in more detail.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"245-254"},"PeriodicalIF":1.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636127","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":"Phenotype-genotype correlation of patients with congenital cataracts and hair anomalies.","authors":"Qiwei Wang, Xiaoshan Lin, Dongni Wang, Tingfeng Qin, Wan Chen, Jingjing Chen, Xulin Zhang, Yongbin Lin, Zhuoling Lin, Jing Li, Xiaoyan Li, J Fielding Hejtmancik, Weirong Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Hair anomalies represent a common associated symptom of congenital cataracts. Early diagnosis is crucial for treatment and predicting prognosis. However, the insidious and nonspecific nature of the symptoms in young children makes diagnosis challenging, often necessitating tools such as whole-exome sequencing (WES) for accurate assessment. This study aims to propose a simple and expedient approach to guide clinical management by analyzing phenotype-genotype correlations.</p><p><strong>Methods: </strong>A prospective cohort study was conducted among participants who underwent clinical examinations and WES between 2021 and 2023. Bioinformatic analysis was performed. In total, 170 unrelated congenital cataract probands were tested. The suspected pathogenic variants were validated through Sanger sequencing in both the probands and available family members. Correlation analyses were then performed, integrating clinical characteristics, cataract phenotype, and genotype data.</p><p><strong>Results: </strong>Nine probands presented with both cataracts and hair anomalies. Potential pathogenic variants were detected in all patients with hair anomalies, including a novel variant in <i>LSS</i>. Phenotype-genotype analysis supports the classification of patients into two groups: hypotrichosis 14 and ichthyosis follicularis with atrichia and photophobia syndrome 2, based on the cataract phenotype, severity of the hair anomalies, and the presence of corneal pannus. These patients should be monitored closely for the development and progression of glaucoma and corneal lesions.</p><p><strong>Conclusions: </strong>We identified nine probands with hair anomalies in our large cohort of congenital cataract probands. Using WES and comprehensive clinical examinations, we established definitive diagnoses, broadened the phenotype and genotype, and proposed phenotype-genotype correlations.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"221-229"},"PeriodicalIF":1.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636097","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":"Unravelling γD-crystallin aggregation pathway to understand cataract formation using fluorescence correlation spectroscopy.","authors":"Mangesh Bawankar, Bhaswati Sengupta, Sujata Malik, Pratik Sen, Ashwani K Thakur","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the aggregation behavior of the γD-crystallin protein in an acidic environment with a focus on the formation of intermediate species. The research employs fluorescence correlation spectroscopy to unravel the intricate molecular events leading to aggregation, contributing to a comprehensive understanding of cataract formation.</p><p><strong>Methods: </strong>The kinetics of γD-crystallin protein aggregation were studied with a reversed-phase high-performance liquid chromatography sedimentation assay, a ThT binding assay, and light scattering. We used fluorescence correlation spectroscopy (FCS) to recognize intermediate aggregate species and characterized them with Fourier transform infrared spectroscopy (FTIR). Further, the morphologic characterization of aggregates was done by transmission electron microscopy (TEM), and their hydrophobic characteristics were analyzed using the 8-anilino-1-naphthalenesulfonic acid binding assay.</p><p><strong>Results: </strong>A negligible lag phase was observed in the aggregation kinetic experiments of the γD-crystallin protein. Pentamer, 25-mer, and higher oligomer intermediates were formed on the aggregation pathway. Conformation studies by FCS and FTIR have shown that oligomers are rich in cross-β sheet and random coil structure; however, they constitute more α-helix and less cross-β sheet structure than fibrils. TEM analysis revealed the approximate size of oligomers (diameter ~10 nm), protofibrils (~15 nm), and fibrils (~15 to ~35 nm).</p><p><strong>Conclusions: </strong>In this study, we reported the presence of various intermediate aggregate species formed on the aggregation pathway of γD-crystallin protein at low pH. This will open new areas of research in understanding the detailed aggregation mechanism and aggregation hotspot within unfolded γD-crystallin monomers. The insights gained will also pave the way for future research in the realm of amyloid formation in cataract.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"231-243"},"PeriodicalIF":1.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636159","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":"Mutations in retinal cyclic nucleotide-gated channels identified in familial cases of inherited retinal dystrophies from Pakistan.","authors":"Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.</p><p><strong>Methods: </strong>The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 known IRD genes. The pathogenicity of candidate variants was assessed using the American College of Medical Genetics and Genomics guidelines. Segregation testing was performed by Sanger sequencing.</p><p><strong>Results: </strong>Results of eight IRD families revealed a total of four reported variants in <i>CNGA3</i> (c.827A>G, c.955T>C, c.1641C>A, c.1810C>T) and three novel variants, including c.1633A>T, c.800G>T, and c.1153T>C in <i>CNGA1</i>, <i>CNGA3</i>, and <i>CNGB3</i> genes, respectively, segregating in each respective family. Among disease-causing variants identified in our study cohort, 87.5% were missense. Furthermore, one of the reported missense variants (i.e., c.1641C>A in <i>CNGA3</i>) was segregating in two unrelated families. All identified variants were homozygous and segregated in an autosomal recessive form.</p><p><strong>Conclusions: </strong><i>CNGA3</i> was the most frequently mutated gene in our study cohort. Only the c.1641C>A variant of <i>CNGA3</i> was repeated in two families, showing genetic diversity. The identification of three novel pathogenic variants in CNG channel genes in the present study reaffirms the allelic and genetic heterogeneity of IRDs in the Pakistani population.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"206-219"},"PeriodicalIF":1.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12645064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636155","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":"Erratum: Ablation of C3 modulates macrophage reactivity in the outer retina during photo-oxidative damage.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"204"},"PeriodicalIF":1.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637587","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":"Unravelling γD-crystallin aggregation pathway to understand cataract formation using fluorescence correlation spectroscopy.","authors":"Mangesh Bawankar, Bhaswati Sengupta, Sujata Malik, Pratik Sen, Ashwani K Thakur","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the aggregation behavior of the γD-crystallin protein in an acidic environment with a focus on the formation of intermediate species. The research employs fluorescence correlation spectroscopy to unravel the intricate molecular events leading to aggregation, contributing to a comprehensive understanding of cataract formation.</p><p><strong>Methods: </strong>The kinetics of γD-crystallin protein aggregation were studied with a reversed-phase high-performance liquid chromatography sedimentation assay, a ThT binding assay, and light scattering. We used fluorescence correlation spectroscopy (FCS) to recognize intermediate aggregate species and characterized them with Fourier transform infrared spectroscopy (FTIR). Further, the morphologic characterization of aggregates was done by transmission electron microscopy (TEM), and their hydrophobic characteristics were analyzed using the 8-anilino-1-naphthalenesulfonic acid binding assay.</p><p><strong>Results: </strong>A negligible lag phase was observed in the aggregation kinetic experiments of the γD-crystallin protein. Pentamer, 25-mer, and higher oligomer intermediates were formed on the aggregation pathway. Conformation studies by FCS and FTIR have shown that oligomers are rich in cross-β sheet and random coil structure; however, they constitute more α-helix and less cross-β sheet structure than fibrils. TEM analysis revealed the approximate size of oligomers (diameter ~10 nm), protofibrils (~15 nm), and fibrils (~15 to ~35 nm).</p><p><strong>Conclusions: </strong>In this study, we reported the presence of various intermediate aggregate species formed on the aggregation pathway of γD-crystallin protein at low pH. This will open new areas of research in understanding the detailed aggregation mechanism and aggregation hotspot within unfolded γD-crystallin monomers. The insights gained will also pave the way for future research in the realm of amyloid formation in cataract.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"190-202"},"PeriodicalIF":1.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554017","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":"Mutation of beta-tubulin 4B gene (<i>TUBB4B)</i> causes autosomal dominant retinitis pigmentosa with sensorineural hearing loss in a multigenerational family.","authors":"Cheryl Y Gregory-Evans, Aaron W Joe, Kevin Gregory-Evans","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Members of a multigenerational Canadian family presented to an inherited retinal degeneration (IRD) clinic with retinitis pigmentosa (RP) and sensorineural hearing loss, reminiscent of an Usher syndrome phenotype. Biallelic disease-causing variants in the known Usher syndrome genes were not identified. Therefore, we enrolled further family members in this study and examined whether other IRD gene variants could explain the phenotype in the family.</p><p><strong>Methods: </strong>Family members underwent a comprehensive ophthalmic examination, including best-corrected visual acuity, direct and indirect ophthalmoscopy, fundus photography, visual field testing, spectral-domain optical coherence tomography, audiological examination, and genetic testing. Some patients also had autofluorescence imaging. Loss-of-function testing was initiated by antisense morpholino knockdown of <i>tubb4b</i> in zebrafish.</p><p><strong>Results: </strong>Multimodal clinical testing in affected patients revealed an autosomal dominant late-onset presentation of RP associated with progressive, bilateral sensorineural hearing loss that occurred in the second to third decades of life with no vestibular involvement. Panel-based genetic testing revealed a heterozygous c.1168C>T, p.Arg390Trp variant in the beta-tubulin 4B gene (<i>TUBB4B</i>) only in affected family members. Based on <i>in silico</i> analysis, segregation analysis through the family, and literature evaluation, this variant is likely to be the disease-causing variant inherited in an autosomal dominant manner. We searched our local database of ~1,000 patients with IRD, and no other <i>TUBB4B</i> variants were identified, confirming this is a rare disease variant. Knockdown of <i>tubb4b</i> in zebrafish revealed cone and rod photoreceptor abnormalities in the retina and hydrocephalus in the developing brain, resulting in early larval lethality.</p><p><strong>Conclusions: </strong>For the first time, we describe a multigenerational family with a <i>TUBB4B</i> gene variant p.(Arg390Trp) segregating with deaf-blindness, establishing autosomal dominant inheritance. This further confirms that the Arg390 codon is a mutation hotspot. We also expand the range of phenotypes seen with the p.(Arg390Trp) <i>TUBB4B</i> gene variant to include typical RP as well as a milder, pericentral RP. Furthermore, our studies suggest there is conservation of TUBB4B ciliary function between zebrafish and humans, making zebrafish a better model system for studying vision loss than the mouse model.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"175-188"},"PeriodicalIF":1.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554016","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":"Inhibitory effects of ursolic acid on oxygen-induced mouse retinal neovascularization via intravitreal injection.","authors":"Lu Yang, Fen Yang, Weiliang Zhang, Yanhua Wang, Peng Chen, Shufang Du, Xiaoyan Liu, Yan Gao, Junhua Shi, Peng Wang, Rui Li, Qiang Su","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Objective: This study aimed to explore the effects and mechanisms of ursolic acid (UA) on oxygen-induced retinal neovascularization (RNV) in mice and its inhibitory effects on human retinal capillary endothelial cells (HRCECs) under high-glucose conditions.</p><p><strong>Methods: </strong>Neonatal mice were divided into five groups: one normal group and four with oxygen-induced retinopathy (OIR), including OIR, phosphate-buffered saline, UA and Lucentis groups. On postnatal day 17 (P17), mice were euthanized and one eye was collected for retinal analysis using fluorescence microscopy. Protein and messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and cyclo-oxygenase-2 (COX-2) were detected. HRCECs cultured under high-glucose conditions were treated with UA to assess its effects on proliferation and molecular expression.</p><p><strong>Results: </strong>UA significantly reduced RNV area in OIR mice and protected astrocytes from hypoxia-induced damage (p<0.01). VEGF, MMP-2, MMP-9 and COX-2 levels were lower in the UA group compared with the OIR and phosphate-buffered saline groups (p<0.05), but slightly higher than in normal controls (p<0.01). Lucentis reduced VEGF levels but did not significantly affect MMP-2, MMP-9 or COX-2. In HRCECs, UA inhibited high-glucose-induced proliferation and reduced VEGF, MMP-2, MMP-9 and COX-2 expression in a time- and dose-dependent manner.</p><p><strong>Conclusions: </strong>UA inhibits RNV by reducing VEGF, MMP-2, MMP-9 and COX-2 expression, protecting astrocytes and suppressing HRCEC proliferation under high-glucose conditions, highlighting its therapeutic potential for retinal neovascular diseases.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"160-173"},"PeriodicalIF":1.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554015","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}