Molecular Vision最新文献

{"title":"A novel <i>PRDM13</i> gene duplication causing congenital North Carolina macular dystrophy phenotype in a Mexican family.","authors":"Oscar Francisco Chacon-Camacho, Luis Leonardo Flores-Lagunes, Kent W Small, Nitin Udar, Uma Udar, Amber Diaz, Rocío Arce-González, Carolina Molina-Garay, Alan Martínez-Aguilar, Luis Montes-Almanza, Froylan Garcia-Martinez, Adriana Gudiño, Rodrigo Matsui-Serrano, Scarlett Fest-Parra, Carmen Alaez-Verson, Fadi Shaya, Juan Carlos Zenteno","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>North Carolina macular dystrophy (NCMD) is a rare autosomal dominantly inherited congenital maculopathy caused by either non-coding point mutations or tandem duplications in the DNase I hypersensitivity site DHS6S1, at chromosome 6q16 (MCDR1), or at chromosome 5 (MCDR3). To date, at least 30 NCMD pedigrees from different ethnicities have been genetically identified worldwide. Herein, we report the clinical and genetic features of a newly found NCMD family in Mexico with a novel tandem duplication involving both the DNASE1 site and the <i>PRDM13</i> gene.</p><p><strong>Methods: </strong>Seven affected subjects from a Mexican family underwent a complete ophthalmic assessment that included dilated indirect ophthalmoscopy, fundus photography, optical coherence tomography (OCT), fundus autofluorescence (FAF), kinetic and chromatic perimetry, and electroretinography (ERG). Next-generation sequencing (NGS), followed by array-based comparative genomic hybridization (array-CGH) and quantitative polymerase chain reaction (qPCR) analyzes, were employed to demonstrate the causative molecular defect.</p><p><strong>Results: </strong>All seven affected patients had a severe appearing phenotype characterized by symmetric excavated atrophic coloboma-like chorioretinal macular lesions. In addition, using OCT, lacunae in the inner retinal layers and inner retinal loss were observed in all patients. NGS identified a heterozygous tandem duplication of the entire coding sequence of the <i>PRDM13</i> gene in all seven affected individuals, whereas subsequent array CGH, NGS, and Sanger sequencing allowed for the identification of the precise boundaries of a ~148 kb MCDR1 duplication containing the whole <i>PRMD13</i> gene and the DNASE1 site.</p><p><strong>Conclusions: </strong>The phenotypic features in this NCMD pedigree continue to support the concept that this disorder is a congenital macular malformation rather than a progressive dystrophic entity. Unlike most NCMD families, there was no variable expressivity found in this study, possibly due to the relatively small size of the family. The other hypothesis is that the duplication involves genomic segments that are more consistently or tightly bound to other regulatory regions of PRDM13. The identification of a novel causative tandem duplication involving the DNASE1 site and the <i>PRDM13</i> gene in this family allows for the expansion of the mutational spectrum of the disease.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"400-408"},"PeriodicalIF":1.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433133","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":"The association of endothelial nitric oxide synthase (<i>eNOS</i>) gene polymorphisms and diabetic retinopathy among patients with type 2 diabetes: A case-control study.","authors":"Diala W Abu-Hassan, Muawyah D Al-Bdour, Iman Aolymat, Mohammed El-Khateeb","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic patients experience chronic hyperglycemia that increases oxidative stress by enhancing free radical formation and nitric oxide (NO) production. Genetic mutations in the endothelial nitric oxide synthase (<i>eNOS</i>) enzyme gene affect the levels of NO formation. These mutations, together with chronic hyperglycemia, may increase the risk of diabetic retinopathy (DR) development and/or DR progression as a complication of diabetes. This study aimed to determine whether the <i>eNOS</i> polymorphisms intron 4ab, exon 7 Glu298Asp variant (G894T), and T-786C are associated with DR severity.</p><p><strong>Methods: </strong>This case-control study involved 250 subjects (172 with type 2 diabetes mellitus (DM) with or without DR and 78 healthy controls). DR was detected by slit lamp biomicroscopy and its severity was determined with the evidence-based International Clinical Diabetic Retinopathy Disease Severity Scale. The genotyping of eNOS polymorphisms was analyzed by polymerase chain reaction (PCR) only or with restriction fragment length polymorphism. The haplotype analysis was performed using the SNPStats tool.</p><p><strong>Results: </strong>The genotype distribution for the three polymorphisms was significantly different in patients with diabetes compared to controls (intron 4 ab: a/a, 1.7%; a/b, 20.4%; b/b, 77.9%. G894T: GG, 56.4%; GT, 34.3%; TT, 9.3%. T-786C: TT, 58.2%; TC, 33.5%; CC, 8.3%). Differences in genotype or allele frequency was non-significant between subjects with diabetes and DR compared to those without DR, except the C allele of the T-786C polymorphism was significantly less common in DR patients. DR severity was not affected by any polymorphisms. Haplotypes bTC and aTT were significantly less common or more prevalent in DR than DM patients, respectively.</p><p><strong>Conclusions: </strong>We demonstrated that type 2 DM patients exhibited a higher prevalence of the three polymorphisms when compared to the control group. The C allele of T-786C polymorphism may have a protective effect against DR. Also, none of the mutations was correlated with a higher DR risk nor with the severity of DR. Haplotype aTT increased the risk for DR, while the bTC haplotype reduced it.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"390-398"},"PeriodicalIF":1.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433535","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":"Global mapping of BMAL1 protein-DNA interactions in human retinal Müller cells.","authors":"Qianyi Luo, Neel Sangani, Surabhi Abhyankar, Sahiti Somalraju, Sarath Chandra Janga, Ashay D Bhatwadekar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The circadian clock, a conserved biologic timekeeping mechanism, is pivotal in orchestrating rhythmic physiologic processes. While extensively studied in the central clock, the involvement of BMAL1 in peripheral clocks, particularly in human Müller cells, remains underexplored. Müller cells, critical for retinal homeostasis, may unveil novel insights into circadian regulation. Employing ChIP-sequencing, we comprehensively mapped BMAL1 binding sites in human Müller cells. The analysis identified 275 reproducible peaks, with predominant distribution across promoters (26.6%), intronic (26.3%), and intergenic (22.1%) regions, with 80% of these confident peaks linked to protein-coding genes. Differential peak analysis revealed 89 unique genes significantly enriched with BMAL1 sites in their promoters, while functional enrichment of the associated genes indicated key biologic processes such as circadian regulation of gene expression, photoperiodism, and glucocorticoid receptor signaling pathway regulation. Motif analysis revealed a highly conserved 6-nucleotide motif, CACGTG, appearing in 89.09% of the peaks. Analysis of the binding sites across genomic regions highlighted the robust BMAL1 binding, further confirmed by qPCR validation of circadian targets such as G6PC3, CIART, PER1, and TXNIP, which are critical for Müller cell health, along with SHMT2 and MALAT1, which have emerged as novel genes that may have implications for Müller cell health. Our findings unveil the regulatory landscape of BMAL1 in Müller cells, contributing to a broader understanding of the clock-mediated mechanism in ocular tissues. These insights hold therapeutic potential for circadian-related retinal diseases, presenting avenues for chronotherapeutic interventions.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"379-389"},"PeriodicalIF":1.4,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433439","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":"Expression of cytokines in the aqueous humor of cataract patients with pathologic myopia and simple high myopia.","authors":"Xue Han, Yaru Hu, Yue Chen, Jinbiao Cai, Yaru Chen, Na Li, Che Xu, Qi Zhou, Fengchao Wang, Jianfeng Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the role of cytokines during the progression process of cataract patients with pathologic myopia (PMC) and simple high myopia (SHMC).</p><p><strong>Methods: </strong>A total of 63 cataract patients who underwent cataract surgery were classified into a PMC group (22 eyes), an SHMC group (21 eyes), and an age-related cataract (ARC) group (20 eyes), based on axial length (AL) and International Myopia Institute (IMI)'s classification. Aqueous humor samples were extracted before surgery. Cytometric bead array (CBA) was employed to measure the level of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), interleukin-10 (IL-10), interleukin-17a (IL-17a), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor -α (TNF-α), intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM). Additionally, the correlations between cytokines and the AL or myopic maculopathy categories were examined.</p><p><strong>Results: </strong>VEGF, IL-6, MCP-1, ICAM, and VCAM (all p<0.001), TGF-β1 (p=0.018), and IL-8 (p=0.008) were statistically different among the three groups. In parallel, the levels of VCAM (<i>r</i>=0.718), MCP-1 (<i>r</i>=0.591), ICAM (<i>r</i>=0.584), IL-8 (<i>r</i>=0.435), IL-6 (<i>r</i>=0.396), and TNF-α (<i>r</i>=0.280) were positively associated with myopic maculopathy, while VEGF (<i>r</i>=-0.542), TGF-β1 (<i>r</i>=-0.381), and IL-17a (<i>r</i>=-0.284) were correlated inversely with myopic maculopathy (all p<0.05). Furthermore, a significant positive correlation was observed between AL and levels of VCAM (<i>r</i>=0.726), MCP-1 (<i>r</i>=0.644), ICAM (<i>r</i>=0.573), IL-6 (<i>r</i>=0.386), and IL-8(<i>r</i>=0.376). VEGF (<i>r</i>=-0.610), TGF-β1 (<i>r</i>=-0.361), and IL-17a (<i>r</i>=-0.319) were inversely associated with AL (all p<0.05). Further analysis using multiple regression indicated that, after adjusting for confounding factors, lower VEGF and higher VCAM were significantly associated with AL. However, the limitations of this study were reflected in the inability to determine whether the changes in cytokines were the consequences or causes of the formation of high myopia.</p><p><strong>Conclusions: </strong>The pathogeneses of PMC and SHMC may differ, and there are significant changes associated with inflammation and the immune response in eyes with PMC.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"369-377"},"PeriodicalIF":1.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433426","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":"WTAP-mediated N6-methyladenosine mRNA methylation regulates laser-induced macular neovascularization.","authors":"Qingyun Gong, Liting Hu, Guibo Liu, Xiaoni Yin, Xiaoran Zhao, Qinghua Li, Ying Li, Yibin Sun, Yuzheng Zhou, Chunyan Guo, Zhaodong Du","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Neovascular age-related macular degeneration (nAMD) is now a major cause of central vision loss in older adults worldwide. The primary characteristic of nAMD is the formation of macular neovascularization (MNV), which is a pathologic form of angiogenesis. Epigenetics plays a role in multiple pathological physiologic processes. N6-methyladenosine (m6A) modification is the most common, abundant, and reversible modification in eukaryotic mRNAs, and it plays a role in various pathological angiogenesis processes. This study intends to reveal the expression and functions of m6A during the macular neovascularization (MNV) process.</p><p><strong>Methods: </strong>A laser-induced MNV mouse model was used in this study. m6A quantitative analysis was performed to detect the expression of m6A. Subsequently, the expression of various m6A writers and erasers was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Immunohistochemistry was used to detect Wilms' tumor 1-associating protein (WTAP) expression in the MNV lesions. Intravitreal injection of WTAP siRNA in MNV mice to silence the WTAP gene. Hematoxylin and eosin (H&E) were used to determine the thickness and length of the MNV. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were examined to measure the leakage area of the MNV. Proliferating cell nuclear antigen (PCNA) expression was detected with a western blot. The mRNA and protein levels of β-catenin were tested with qRT-PCR and western blot.</p><p><strong>Results: </strong>We found increased m6A modification levels after laser induction compared with the normal control group. Subsequently, the expression of various m6A writers and erasers was detected. The results showed that WTAP increased in the MNV model in mice. After the injection of WTAP siRNA into the vitreous body, the expression of WTAP significantly decreased, subsequently decreasing the m6A modification levels. The width, breadth, and leakage area of MNV damage markedly decreased, and endothelial cell proliferation was inhibited. After laser-induced MNV, the expression of β-catenin increased, and that of β-catenin significantly decreased after WTAP knockout.</p><p><strong>Conclusions: </strong>In conclusion, this study suggests that WTAP-mediated m6A methylation can regulate pathological angiogenesis during MNV and that WTAP may participate in the formation of MNV through the wingless-related integration site (Wnt) pathway. WTAP may be a potential target for MNV treatment.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"336-347"},"PeriodicalIF":1.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013888","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":"Human lens epithelial cells induce the inflammatory response when placed into the lens capsular bag model of posterior capsular opacification.","authors":"Samuel G Novo, Adam P Faranda, Justin C D'Antin, Yan Wang, Mahbubul Shihan, Rafael I Barraquer, Ralph Michael, Melinda K Duncan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Cataracts are typically treated by phacoemulsification followed by intraocular lens implantation. Studies of mouse models of cataract surgery have revealed that lens epithelial cells rapidly remodel their transcriptome to express proinflammatory cytokines after lens fiber cell removal, but it is currently unknown whether this response is conserved in human lenses. This study seeks to fill this knowledge gap.</p><p><strong>Methods: </strong>Human cadaver eyes from 70 to 89 year old individuals were prepared for the human capsular bag model of cataract surgery. The central epithelium was preserved in RNAlater during culture preparation, then the equatorial epithelium was either immediately preserved in RNAlater after the culture was created, or 24 h later. Gene expression profiles were generated by bulk sequencing of RNA isolated from these tissue samples. The transcriptomic response of human cadaver-derived lens epithelial cells to culture in this \"capsular bag\" model was characterized by bioinformatic analysis. The human response was directly compared to that of 24-month-old mouse lens epithelial cells subjected to fiber cell removal surgery.</p><p><strong>Results: </strong>Human lens epithelial cells remodel approximately a third of their transcriptome by 24 h after surgery, and like mice, this response consists of induction of proinflammatory cytokine genes, upregulation of fibrotic markers and downregulation of genes controlling the lens epithelial phenotype.</p><p><strong>Conclusions: </strong>These observations demonstrate that humans and mice have similar responses to cataract surgery and support the use of mice to study the response of lens epithelial cells to cataract surgery, suggesting that identified injury response mechanisms can be leveraged to elucidate new approaches to improve the outcomes of cataract surgery.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"348-367"},"PeriodicalIF":1.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433363","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":"The interactions between <i>ARMS2</i>, <i>CFH</i>, <i>VEGF-A</i> and environmental factors on the risk of age-related macular degeneration.","authors":"Ariunzaya Altankhuyag, Chimedlkhamsuren Ganbold, Bayarlakh Byambadorj, Suvd Tumurbaatar, Purevsuren Sodnomtseren, Uranchimeg Davaatseren, Sarantuya Jav","doi":"","DOIUrl":"","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Age related macular degeneration (AMD) is a multifactorial disease caused by a combination of environmental and genetic factors. The prevalence of allele and genotypeof AMD-related genes is varied throughout the world due to racial and ethnic differences. Number of previous studies have shown that the polymorphisms in the &lt;i&gt;ARMS2&lt;/i&gt;, &lt;i&gt;CFH&lt;/i&gt; and &lt;i&gt;VEGF-A&lt;/i&gt; genes are associated with AMD. In Mongolia, there is a lack of sufficient data on AMD development in its population and thus needs more studies on the topic. Therefore, it needs more studies about AMD development in the population. For this reason, we have investigated several specified polymorphisms in &lt;i&gt;CFH&lt;/i&gt;, &lt;i&gt;VEGF-A&lt;/i&gt; and &lt;i&gt;ARMS2&lt;/i&gt; genes to reveal a relationship with AMD and determine the prevalence of alleles and genotypes of the genes in Mongolian population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Totally 161 AMD patients and 223 controls were enrolled in this case-control study. The polymorphisms in &lt;i&gt;CFH&lt;/i&gt;, &lt;i&gt;ARMS2&lt;/i&gt; and &lt;i&gt;VEGF&lt;/i&gt;-&lt;i&gt;A&lt;/i&gt; were detected by using the methods of allele-specific polymerase chain reaction (ASPCR) and PCR based restriction fragment length polymorphism (RFLP). Statistical analysis were performed by STATA 13.0, SNPAlyze 9.0 and MDR 3.0.2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;According to the study result, the characteristics of hypertension, constant-wearing sunglasses and anticoagulant medications in AMD group were significantly different from those in the control group. As for the dominant model, T allele of &lt;i&gt;ARMS2&lt;/i&gt; rs10490924 (cOR=4.45; 95% CI, 2.44-8.13, p&lt;0.001, aOR=5.08; 95% CI, 2.70-9.59, p&lt;0.001) was more frequent among patients with AMD in comparison with the control group. Also, G/G genotype of &lt;i&gt;CFH&lt;/i&gt; rs800292 (cOR=11.61; 95% CI, 3.41-39.51, p&lt;0.001, aOR=12.49; 95% CI, 3.47-44.91, p&lt;0.001) and G/G genotype of &lt;i&gt;CFH&lt;/i&gt; rs1065489 (cOR=4.19; 95% CI, 2.53-6.93, p&lt;0.001, aOR=4.67; 95% CI, 2.71-8.05, p&lt;0.001) were significantly higher in AMD group after Bonferroni correction. This result suggests that people who carrying the risk genotypes of these polymorphisms had an increased risk for AMD development. As for the models of three or more SNP interactions, the participants with any combinations of risk genotypes have 6 to 106-fold higher risk for AMD development. This result suggests that there is some positive-additive interaction existing between the genetic variants of &lt;i&gt;ARMS2&lt;/i&gt;, &lt;i&gt;CFH&lt;/i&gt; and &lt;i&gt;VEGF-A&lt;/i&gt; genes for AMD development. Our study also revealed that the participants with hypertension and carrying G/G for rs1065489 in &lt;i&gt;CFH&lt;/i&gt; gene or non G/G for rs10490924 in &lt;i&gt;ARMS2&lt;/i&gt; gene genotypes had 9 to 14 times higher risk for AMD development (cOR=9.05; 95% CI, 4.38-18.68, p&lt;0.001, RERI=4.546; AP=0.502, S=2.298, cOR=13.98; 95% CI, 3.19-61.1, p&lt;0.001, RERI=5.85; AP=0.419, S=1.821) with high level of significance. Moreover, it was found that the participants who avoided wearing sunglasse","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"320-335"},"PeriodicalIF":1.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433493","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":"Caveolin-1 regulates inflammatory mediators in retinal endothelial cells.","authors":"Youde Jiang, Li Liu, Mohamed Al-Shabrawey, Jena J Steinle","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"298-303"},"PeriodicalIF":1.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433374","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 implications of CHST6 gene mutations and their corneal microstructural changes in macular corneal dystrophy patients.","authors":"Durga Murugan, Roopam Duvesh, Sindhura Devi Adsumilli, Namperumalsamy Venkatesh Prajna, Prakash Chermakani, Periasamy Sundaresan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To collectively investigate the carbohydrate sulfotransferase 6 (CHST6) mutation spectrum and corneal morphological alterations of macular corneal dystrophy (MCD) patients using in vivo confocal microscopy (IVCM), histochemistry, immunohistochemistry, and further ascertaining the immunophenotype using an enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Methods: </strong>Sanger sequencing-based CHST6 gene screening was performed for 112 study participants (MCD patients, n = 68; family members, n = 44). Twenty-seven MCD patients underwent IVCM analyses, and corneal buttons were analyzed with histochemistry Alcian blue (AB) staining and immunohistochemistry anti-keratan sulfate (KS) monoclonal antibody, 5D4MoAb. An ELISA was used to determine serum KS levels. Quantitative analysis of the central corneal thickness (CCT), epithelial cell thickness, epithelial cell count, and stromal keratocyte cell count was performed using a one-way ANOVA.</p><p><strong>Results: </strong>Eighteen distinct CHST6 mutations, including one novel (p.L129V), were identified. MCD patients with predominant immunophenotype IA (n = 15) harboring major p.Q182Rfs199 deletion, p.194_R196delinsRC (delins), and open reading frame (ORF) mutations displayed AB positivity corresponding to loss of Bowman's layer, interlamellar glycosaminoglycan (GAG) depositions, and faint KS expression (5D4-MoAb) only in stromal keratocytes. Notably, IVCM imaging revealed BL loss due to confluent clumps of hyper-reflective, granular deposits together with scar tissue seen only in this group. Eight patients (with missense mutations) displayed immunophenotype I with positive GAG deposits and negative KS expression. Patients with immunophenotype II (n = 4) with no mutations showed both positive GAG deposits and KS expression. A quantitative analysis revealed a statistically significant decrease in CCT (p-value < 0.001), epithelial cell thickness, epithelial cell count, and stromal keratocyte cell count among the patients with truncation mutations compared to the control group.</p><p><strong>Conclusions: </strong>In this current study, the combinational findings of MCD-related corneal morphological alterations, immunophenotypes, and mutation spectrum are presented first, which indicated a severe phenotype in patients identified with truncation (deletion, delins, and deletion of ORF) mutations. However, additional studies with a larger number of patients would help highlight these findings and reinforce the possible correlation between genotypes and immunophenotypes in MCD pathogenesis.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"305-318"},"PeriodicalIF":1.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433435","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: A method for gene knockdown in the retina using a lipid-based carrier.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"289"},"PeriodicalIF":1.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676209","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}