Molecular Vision最新文献

{"title":"Genetic and clinical characterization of suspected retinitis pigmentosa in a cohort of Brazilian patients.","authors":"Sarah Pereira de Freitas Cenachi, Maria Frasson, Anna Laura Marques Nascentes, Anna Luiza Braga Albuquerque, Rodrigo Rezende Arantes, Virgínia Mares, Luiz Armando Cunha De Marco, Márcio Bittar Nehemy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To identify causative genetic variants and associated clinical phenotypes in patients of a tertiary referral center in Brazil with suspected retinitis pigmentosa (RP).</p><p><strong>Methods: </strong>RP diagnosis was established based on predefined clinical criteria. The patients underwent detailed ophthalmologic assessments and multimodal retinal imaging. Genomic DNA was analyzed using a next-generation sequencing (NGS) panel targeting 238 genes associated with inherited retinal diseases.</p><p><strong>Results: </strong>Among 55 patients, the genetic diagnostic yield was 71% (39/55), with 13 novel variants identified. The most frequently implicated genes were <i>RHO</i>, <i>RPGR</i>, and <i>USH2A</i>, accounting for approximately 50% of genetically diagnosed cases. Fundus autofluorescence revealed patchy hypoautofluorescence surrounding the vascular arcades as the most frequent finding. On spectral-domain optical coherence tomography, the pattern of ellipsoid zone presentation in the central macula was significantly correlated with best-corrected visual acuity (p<0.001).</p><p><strong>Conclusions: </strong>This study delineates the genetic and phenotypic spectrum of RP in a tertiary Brazilian referral center, highlighting the utility of NGS for molecular diagnosis and clinical management.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"526-537"},"PeriodicalIF":1.8,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499085","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":"Ferroptosis related genes in retinopathy of prematurity: Screening for potential pharmacological targets.","authors":"Qiujuan Liao, Suyu Liu, Liqing Wei, Yuli Cai, Ying Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To elucidate the molecular mechanisms of retinopathy of prematurity (ROP) and identify potential drug targets for its treatment based on bioinformatics analysis.</p><p><strong>Methods: </strong>We obtained gene expression profiles from data sets GSE123945 and GSE135844 in the Gene Expression Omnibus database. Differential expression analysis was performed on GSE135844 to identify differentially expressed genes (DEGs). Ferroptosis-related genes were retrieved from FerrDb, and Venn diagrams were used to identify overlapping genes between DEGs and ferroptosis-related genes. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis, were conducted to explore the biological roles of these genes. Protein-protein interaction networks were constructed using the STRING database, and hub genes were identified using Cytoscape. Potential drug targets were screened using the Drug-Gene Interaction Database.</p><p><strong>Results: </strong>We identified 23 DEGs associated with ferroptosis in ROP. These genes were significantly enriched in biological processes such as angiogenesis, vasculature development, and wound healing. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the PI3K-Akt signaling pathway plays a central role in ROP pathogenesis. Gene set enrichment analysis identified the defense response as the most significantly enriched gene set. Hub genes, including <i>HMOX1, ALB</i>, and <i>JUN</i>, were identified through protein-protein interaction network analysis. Potential drugs targeting these hub genes, such as stannsoporfin, recombinant neurotrophic factors, zinc chloride, and irisolidone, were identified using the Drug-Gene Interaction Database.</p><p><strong>Conclusions: </strong>Our study demonstrates the utility of bioinformatics approaches in identifying ferroptosis-related genes and potential drug targets for ROP. The findings provide a foundation for further experimental validation and the development of novel therapeutic strategies for ROP.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"515-524"},"PeriodicalIF":1.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499490","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":"Deciphering the genetic basis of inherited retinal dystrophies via whole-exome sequencing in a Turkish cohort.","authors":"Zulal Keles, Ozlem Ural Fatihoglu, Ziya Ayhan, Ali O Saatci, Ahmet O Caglayan, Ayfer Ulgenalp","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Inherited retinal dystrophies (IRDs) encompass a genetically and clinically heterogeneous group of disorders, with over 300 genes currently implicated. Early and precise genetic diagnosis is critical for advancing targeted gene therapies and personalized treatment strategies. This study aims to investigate genetic findings in IRDs using whole-exome sequencing (WES) in a cohort of affected individuals.</p><p><strong>Methods: </strong>WES was performed on 34 unrelated probands diagnosed with diverse IRD subtypes. Variant analysis focused on identifying clinically relevant variants consistent with the patients' phenotypes and inheritance patterns, emphasizing novel and rare variants.</p><p><strong>Results: </strong>Clinically relevant variants consistent with the patients' phenotypes and inheritance patterns were identified in 24 cases. Among these, four variants were novel: <i>RP2</i> c.181_182del, <i>CYP4V2</i> c.377T>G, <i>RPGR</i> c.1414G>A, and <i>RPE65</i> c.267C>G. Additionally, we identified a patient with isolated IRD carrying a homozygous <i>IFT81</i> c.1969C>T (p.Gln657Ter) variant, a gene typically associated with syndromic phenotypes. Furthermore, we reported a relatively rare presentation of ARSG-related Usher syndrome in a patient harboring a homozygous <i>ARSG</i> c.263G>T (p.Arg88Leu) alteration.</p><p><strong>Conclusions: </strong>This study underscores the diagnostic power of WES in IRDs, revealing novel variants and supporting its integration into clinical practice to enhance early diagnosis and enable precision medicine.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"502-513"},"PeriodicalIF":1.8,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499451","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":"Targeted sequencing with single-molecule molecular inversion probes highlights a gap in understanding the cause of Fuchs endothelial corneal dystrophy.","authors":"Bushra Alayed, Danah Albuainain, Salina Siddiqui, Weijia Li, Ummey Hany, Seema Anand, Chris F Inglehearn, Christopher M Watson, Manir Ali","doi":"","DOIUrl":"","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;A trinucleotide repeat expansion in &lt;i&gt;TCF4&lt;/i&gt; is thought to cause Fuchs endothelial corneal dystrophy (FECD) in ~70% of European patients. In addition, strong evidence exists for the involvement of rare variants in &lt;i&gt;COL8A2&lt;/i&gt; and &lt;i&gt;SLC4A11&lt;/i&gt; in a small number of FECD cases, and more controversially, it has been suggested that variants in &lt;i&gt;ZEB1&lt;/i&gt;, &lt;i&gt;AGBL1&lt;/i&gt;, and &lt;i&gt;LOXHD1&lt;/i&gt; may also be involved. We screened patients without a &lt;i&gt;TCF4&lt;/i&gt; repeat expansion for causative variants in the other candidate FECD genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Genomic DNA from blood was genotyped for expansion of the CTG18.1 repeat in intron 2 of &lt;i&gt;TCF4&lt;/i&gt; using short-tandem repeat PCR, followed by triplet-repeat primed PCR (STR/TP-PCR). Single-molecule molecular inversion probes (smMIPs) were designed to amplify the coding exons and splice recognition sites of FECD candidate genes &lt;i&gt;COL8A2&lt;/i&gt;, &lt;i&gt;SLC4A11&lt;/i&gt;, &lt;i&gt;ZEB1&lt;/i&gt;, &lt;i&gt;AGBL1&lt;/i&gt;, and &lt;i&gt;LOXHD1&lt;/i&gt; using MIPGEN, and the libraries generated were sequenced on a NextSeq 2000. FASTQ-formatted sequence reads were aligned to the human reference genome with MIPVAR, and identified variants were annotated using Annovar. Rare potentially pathogenic variants (minor allele frequency ≤0.01 for assumed dominant inheritance, combined annotation-dependent depletion ≥15) were confirmed by Sanger sequencing and interpreted according to American College of Medical Genetics and Genomics criteria using the Franklin by Genoox interface.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Analysis of 114 FECD cases by STR/TP-PCR stratified the patients into FECD expansion-negative cases that had &lt;50 trinucleotide repeats on both alleles at the CTG18.1 locus (n = 33 probands and three additional family members) and FECD expansion-positive (n = 78) cases with at least one allele harboring ≥50 repeats in size. All 36 expansion negative cases were then analyzed by smMIP targeted capture and short-read sequencing of the five other genes implicated in FECD causation. For comparison, two control groups were similarly analyzed: a subset of 29 of the expansion-positive cases whose FECD was assumed to be caused by the repeat expansion and 29 expansion-negative unaffected individuals. Across all groups, 13 variants passed filtration criteria: 1 in &lt;i&gt;COL8A2&lt;/i&gt;, 2 in &lt;i&gt;SLC4A11&lt;/i&gt;, 4 in &lt;i&gt;AGBL1&lt;/i&gt;, and 6 in &lt;i&gt;LOXHD1&lt;/i&gt;. No variants were identified in &lt;i&gt;ZEB1.&lt;/i&gt; Eight of the variants identified were found in seven FECD expansion-negative cases, five in four FECD expansion-positive cases, and three in two non-FECD controls, with three variants appearing in both expansion-positive and expansion-negative patient groups. Statistical analysis indicated no significant enrichment of variants in expansion-negative cases compared to the other two groups (&lt;i&gt;p&lt;/i&gt; = 0.7612 and 0.3275). Only one variant (&lt;i&gt;LOXHD1&lt;/i&gt; NM_144612.7, c.5545G&gt;A, p.(Gly1849Arg)), found in an expansion-negative case, was classified as likel","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"486-500"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016412","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":"Unfolded proteins and aggregates: The role of proteostasis in pseudoexfoliation pathology.","authors":"Bushra Hayat, Debasmita Pankaj Alone","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Proteostasis impairment is central to cellular dysfunction in protein aggregation disorders such as Alzheimer disease, Parkinson disease, and age-related macular degeneration. Pseudoexfoliation (PEX), a systemic age-related disorder and a leading cause of secondary glaucoma, is increasingly recognized as a protein aggregation disease. It is characterized by the deposition of pseudoexfoliative material (PEXM) in ocular tissues, leading to elevated intraocular pressure and optic neuropathy.</p><p><strong>Objective: </strong>This review synthesizes current evidence on the role of proteostasis failure in PEX pathogenesis, with a focus on molecular mechanisms, stress response pathways, and potential therapeutic interventions.</p><p><strong>Methods: </strong>We conducted a comprehensive literature review of studies examining proteostasis mechanisms in PEX. Emphasis was placed on cellular pathways regulating protein synthesis, folding, and degradation, including the unfolded protein response (UPR), ubiquitin-proteasome system (UPS), and autophagy, as well as environmental and aging-related triggers of proteotoxic stress.</p><p><strong>Results: </strong>Evidence indicates that chronic proteotoxic stress, arising from aging, oxidative damage, and environmental influences, disrupts the proteostasis network (PN). Dysregulation of ER stress signaling, cytosolic stress responses, and protein degradation pathways contributes to the accumulation of misfolded proteins and extracellular matrix deposits in ocular tissues. These molecular alterations underlie disease onset and progression in PEX syndrome (PEXS) and PEX glaucoma (PEXG).</p><p><strong>Conclusions: </strong>Proteostasis dysfunction plays a pivotal role in PEX pathogenesis by promoting protein misfolding, aggregation, and extracellular deposition. Targeting the proteostasis network, through modulation of stress responses and enhancement of degradation pathways, represents a promising therapeutic strategy for PEXS and PEXG.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"463-484"},"PeriodicalIF":1.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513405","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":"Genetic phenotypic characteristics and inheritance patterns of patients with achromatopsia at a large academic institution and a review of the literature and gene therapies.","authors":"Sanjana Molleti, Pedro F Monsalve, Richard N Sather, Jade Y Moon, Jacie Ihinger, Sandra R Montezuma","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Achromatopsia (ACHM) is a cone dysfunction syndrome associated with low color vision, photophobia, and congenital nystagmus. Pathogenic variants in the <i>CNGA3</i> and <i>CNGB3</i> genes are the most common causes of ACHM. Identifying the underlying genetic etiology in patients with clinical findings of ACHM is critical to establishing the diagnosis and selecting targets for gene therapies. This study utilizes the inherited retinal disease (IRD) database at the University of Minnesota (UMN) to understand clinical features of achromatopsia, potential diagnostic methods, and genetic variability at one large academic institution.</p><p><strong>Methods: </strong>This retrospective cohort study examined patients with a genetically confirmed diagnosis of ACHM evaluated at the UMN/M Health IRD clinic between May 2015 and August 2022. Data were collected through UMN's electronic health record system and included information on demographics, history of ocular illness, visual acuity, and diagnostic exam results, such as electroretinogram, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Genetic testing was performed using next-generation sequencing panels of varying sizes, and variants were interpreted according to American College of Medical Genetics guidelines.</p><p><strong>Results: </strong>A total of 21 patients with a genetically confirmed ACHM were included in the study. Most patients were female (67%) and white (76%). The cohort included one pair of twin siblings and one group of three siblings. The median age of genetic testing conducted was 12 years (interquartile range, 12-20 years). One-third of patients had nyctalopia. All patients experienced difficulties with color vision, 20 of 21 (95.2%) had photosensitivity, and 18 of 21 patients reported congenital nystagmus. Diagnostic imaging showed most patients with a normal scotopic response and absent photopic response on electroretinogram, macular hyperfluorescence on fundus autofluorescence, and normal optical coherence tomography imaging.</p><p><strong>Conclusion: </strong>This study contributes to an understanding of the phenotypes and distribution of genetic variants associated with achromatopsia at a single academic institution in the state of Minnesota, particularly those involving the <i>CNGA3</i> and <i>CNGB3</i> genes. Future research could explore the prevalence of these variants in larger cohorts to enhance clinical management and treatment strategies for patients with achromatopsia.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"454-461"},"PeriodicalIF":1.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499206","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":"System biology analysis reveals that Grm6 is associated with glutamate accumulation-induced scotopic vision impairment in diabetic mice.","authors":"Ying Lian, Yanpu Zhao, Xiaoyu Yang, Hongjie He, Zhanyi Yang, Huanhuan Zhang, Guigang Yan, Lu Lu, Jia Mi, Geng Tian, Yanping Zhu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Scotopic vision impairment as an early event is found in diabetic retinopathy. However, the underlying mechanisms behind hyperglycemia-induced scotopic vision impairment remain unclear. This study aims to identify that Grm6 is associated with glutamate accumulation-induced scotopic vision impairment under hyperglycemia.</p><p><strong>Methods: </strong>In this study, diabetic mice with impaired scotopic vision were induced by streptozotocin, and the retinal electrical activity was evaluated using electroretinography. Label-free quantitative proteomic analysis was used to identify differentially expressed proteins in the retinas of diabetic mice. A retinal transcriptome-wide association analysis and correlation screening were performed in BXD mice strains to explore the potential genes associated with hyperglycemia. Gene function enrichment analysis was used to evaluate gene function and to construct the correlation network.</p><p><strong>Results: </strong>In total, 151 proteins were significantly altered in the retina of diabetic mice. Among these 151 candidates, 22 genes presented a significant correlation with blood glucose level (p<0.05), which were enriched in alanine, aspartate, and glutamate metabolism (p=0.003). Moreover, the glutamate catabolism-related genes Slc1a2, Gad1, and Glud1 were significantly negatively correlated with blood glucose at the transcript and proteome levels, which led to glutamate accumulation under hyperglycemia. Among eight types of metabotropic glutamate receptors, Grm6 had the most significant correlation with blood glucose level (<i>R</i>=-0.5291, p=0.0003). Moreover, Grm6 expression was significantly decreased at both the mRNA and protein levels in the diabetic retina. Gene coexpression network analysis further identified that Grm6 was correlated with Rgs9, suggesting that hyperglycemia may impair scotopic vision via the phototransduction pathway.</p><p><strong>Conclusions: </strong>Our study confirms that Grm6 is associated with scotopic vision impairment induced by glutamate accumulation in diabetic mice and provides an efficient strategy for exploring critical biomarkers and pathways through a combination of proteomics and transcriptome-wide association analysis.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"440-452"},"PeriodicalIF":1.8,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499594","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":"Cassia polysaccharides can regulate the effect of low PAX6 expression on the function of ARPE-19 cells through the Wnt/β-catenin pathway.","authors":"Luo Jincheng, Li Doudou, Li Jialin, Sun Xuewei, Wang Xue, Li Jie, Qiu Hongbin","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the protective effects of cassia polysaccharides on myopia by examining their influence on ARPE-19 cells with reduced PAX6 expression.</p><p><strong>Methods: </strong>The ARPE-19 cell line with diminished PAX6 expression was established using a lentiviral approach and the addition of XAV-939, an inhibitor of Wnt/β-catenin. We assessed the expression of genes and proteins involved in Wnt/β-catenin, scleral remodeling, and cell cycle regulation following treatment with cassia polysaccharides. Gene and protein expression were quantified using reverse transcription PCR and western blot analyses, respectively. Additionally, the migratory capabilities of these cells were evaluated using a scratch assay.</p><p><strong>Results: </strong>Optimal transduction was achieved with a multiplicity of infection of 20, successfully generating a stable ARPE-19 cell line with low PAX6 expression. Cassia polysaccharides did not significantly alter the expression of Wnt2 compared to control groups. Similarly, when treated with XAV-939, β-catenin levels were modified in PAX6-shRNA and XAV-939 but remained unchanged in the cassia polysaccharides. Scleral remodeling markers, including MMP-2 and TGF-β, were elevated, and COL1A1 was decreased in PAX6-shRNA, with no significant changes observed in the cassia polysaccharides. Cell cycle analysis indicated reduced cyclin-dependent kinase 1 and proliferating cell nuclear antigen levels in PAX6-shRNA, with cassia polysaccharides showing no significant effect. Scratch assay results demonstrated slower wound healing in PAX6-shRNA compared to controls over 72 h, with no significant differences observed in the cassia polysaccharides.</p><p><strong>Conclusions: </strong>Cassia polysaccharides may mitigate ARPE-19 cell damage induced by low PAX6 expression through modulation of Wnt/β-catenin, potentially slowing the progression of myopia and offering a protective effect on vision.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"424-438"},"PeriodicalIF":1.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499361","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":"Prevention of diabetic retinopathy in a rat model by a functional food mix.","authors":"Krishna Kalyan Kalahasti, Pandarinath Savitikadi, Ch Uday Kumar, Marka Nagaraju, S Sreenivasa Reddy, G Bhanuprakash Reddy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR), a severe microvascular complication of both type 1 and type 2 diabetes, is one of the leading causes of blindness. Prolonged hyperglycemia leads to vascular endothelial changes, inflammation, neovascularization, and apoptosis through multiple mechanisms, including increased aldose reductase (AR) activity and formation of advanced glycation end products, which contribute to the development of DR. Based on our previous studies with various functional foods that showed AR inhibition and prevented the formation of advanced glycation end products, in this study, a functional food (FF) mix was formulated and investigated its efficacy against DR progression in a rat model.</p><p><strong>Methods: </strong>An FF mix was prepared with powders of amla pericarp, turmeric rhizome, ginger rhizome, cinnamon bark, and black pepper seeds in a specific proportion. Two-month-old Sprague-Dawley rats were grouped into control (C), streptozotocin-induced diabetes (D), and diabetes fed with FF at two levels (FF1, 0.85 g/100 g diet; FF2, 4.25 g/100 g diet) for 6 months from the induction of diabetes. At the end of the experiment, electroretinography was performed, and the eyes were dissected after the animals were sacrificed. A set of eyes was formalin-fixed for histology and immunohistochemistry examination, and the retina from the remaining eyes was used for immunoblotting analysis.</p><p><strong>Results: </strong>Supplementation of FF mix in the diet to diabetic rats has improved retinal function (electroretinography), as well as prevented histomorphological changes and loss of photoreceptor cells (rhodopsin), compared to untreated diabetic rats. Further, FF mix ameliorated hyperglycemia-induced angiogenesis (vascular endothelial growth factor, hypoxia-inducible factor 1α) and gliosis (glial fibrillary acidic protein) in the diabetic rats, accompanied by decreased inflammation (phosphorylated nuclear factor κB, tumor necrosis factor α, monocyte chemoattractant protein 1) and apoptosis (Bax, Bcl2, caspase3, and caspase12).</p><p><strong>Conclusions: </strong>This study illustrates the potential of an FF mix, attributed to the synergistic effects of its components, alleviating the progression of diabetic retinopathy by reducing diabetes-induced hypoxia, gliosis, and inflammation, while also inhibiting apoptosis in retinal cells.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"411-422"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499513","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":"Hyperosmolar stress induces monocyte chemoattractant protein 1 expression in retinal pigmented epithelial arising retinal pigmented epithelial 19 cells.","authors":"Moncef Ould Hamou, Maureen Masset, Célia Weber, Lisa Scifo, Sarah Libert, Angélic Bryla, Françoise Gregoire, Valérie Delforge, Nargis Bolaky, Azine Datlibagi, Jean-Yves Springael, Jason Perret, François Willermain, Christine Delporte","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetes is a chronic inflammatory disease that may damage the blood-retinal barrier, leading to diabetic retinopathy (DR). Blood-retinal barrier rupture may subject the retinal pigmented epithelial cells to a hyperosmolar stress (HOS), activating the transcription factor nuclear factor of activated T cells 5 (NFAT5). In addition, inflammatory cytokines, such as monocyte chemoattractant protein 1 (MCP-1/CCL2), play a crucial role in DR. The aims of our study were to determine whether HOS induces MCP-1 levels in arising retinal pigmented epithelial 19 (ARPE-19) cells and to decipher the responsible intracellular cascade involved in such stimulation.</p><p><strong>Methods: </strong>ARPE-19 cells or ARPE-19 cells transfected with dominant negative NFAT5 plasmid or NFAT5 short hairpin RNA plasmids were preincubated or not for 1 h in the absence or presence of a protein kinase or transcription factor inhibitor and then incubated for 8 h with iso-osmolar or hyperosmolar medium in the absence or presence of inhibitor. NFAT5 reporter gene activity was quantified by luminescence. MCP-1 messenger RNA (mRNA) and protein levels were determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, respectively. Biologically active MCP-1 was assessed by a calcium mobilization assay performed using Chinese hamster ovary cells expressing or not the MCP-1 receptor and apoaequorin.</p><p><strong>Results: </strong>In response to HOS, ARPE-19 cells showed a significant increase in MCP-1 mRNA levels independent of NFAT5 activation. Moreover, the MCP-1 protein secreted by ARPE-19 in response to HOS is biologically active. The use of various inhibitors of protein kinase and transcription factors suggest that the HOS-induced increase in MCP-1 mRNA levels is dependent on a protein kinase C (PKC) and/or a MEK1/2-p38 pathway activating p53, as well as a PKC-p38-PI3K-PDK1-AKT activating hypoxia-inducible factor 1 alpha (HIF1α).</p><p><strong>Conclusion: </strong>HOS increases the expression of MCP-1 mRNA and protein levels in ARPE-19 cells, and the secreted MCP-1 is biologically active. The HOS-induced increase of MCP-1 mRNA appears to be independent of NFAT5 activation. Despite the activation of NFAT5 upon HOS and the presence of NFAT5 binding sites in the MCP-1 gene promoter, activated NFAT5 may not be sufficient to induce MCP-1 gene transactivation in response to HOS in ARPE-19 cells. The intracellular cascade involved in the HOS-induced increase of MCP-1 mRNA in ARPE-19 cells may consist of a PKC-p38-PI3K-PDK1-AKT-HIF1α axis and/or a MEK1/2-p38-p53 axis.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"380-394"},"PeriodicalIF":1.8,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499347","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}