Molecular Vision最新文献

{"title":"Retinal ribbon synapses and the potential functional role of TIAM1: A structural and molecular perspective.","authors":"Martha Emil Adly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Purpose: Retinal and inner ear ribbon synapses are specialized sensory synapses characterized by synaptic ribbons, electron-dense and protein-rich structures that enable rapid and sustained neurotransmitter release. This review aims to examine the molecular architecture of ribbon synapses with a particular focus on the potential involvement of Tiam1, a guanine nucleotide exchange factor implicated in neuronal development and synaptic plasticity.</p><p><strong>Methods: </strong>A comprehensive review of the available literature was conducted to summarize current knowledge on the structural organization and molecular components of ribbon synapses. Particular attention was given to studies investigating Tiam1 expression, function, and its possible role in cytoskeletal remodeling and synaptic regulation.</p><p><strong>Results: </strong>Evidence supports the central role of RIBEYE as the primary structural component of ribbon synapses; however, the regulatory mechanisms governing ribbon formation and function remain incompletely understood. Recent studies suggest a potential contribution of Tiam1 in modulating synaptic organization and function through Rac1 activation and cytoskeletal regulation, although direct experimental evidence in ribbon synapses is still limited.</p><p><strong>Conclusions: </strong>Ribbon synapses are critical for sustained neurotransmission in sensory systems, yet their molecular regulation remains incompletely defined. Tiam1 emerges as a promising candidate molecule that may influence ribbon synapse function. Future experimental studies are needed to clarify its localization, molecular interactions, and contribution to synaptic organization and plasticity.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"131-141"},"PeriodicalIF":1.4,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691053","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":"Analysis of retinal ganglion cell subtypes across six different inbred mouse strains.","authors":"Su-Ting Lin, Fangyu Lin, Jiaxing Wang, Eldon E Geisert","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal ganglion cells (RGCs) are the principal conduits responsible for propagating visual stimuli from the retina to visual centers in the brain. The loss of RGCs leads to visual deficits following trauma or in diseases such as glaucoma. Mouse models are consistently used to investigate root causes for RGC loss. This study quantifies the total number of RGCs and selected RGC subtypes across six strains of inbred mice used in ophthalmic research.</p><p><strong>Methods: </strong>Six mouse strains (C57BL/6J, BALB/cByJ, 129X1/SvJ, A/J, CBA/CaJ, and CAST/EiJ) were selected to represent genetic diversity across the mouse genome. Normal retinas were immunostained for POU6F2, BRN3A, SATB2, OPN4, SMI32, and TO-PRO-3. Cells positively labeled for POU6F2, BRN3A, and SATB2 were quantified using an automated deep learning tool, RGCode. Cells labeled with OPN4, SMI32, and TO-PRO-3 were quantified using the Fiji software.</p><p><strong>Results: </strong>We found statistically significant differences in the quantity (Mean±SEM) and percentage of different RGCs across the inbred mouse strains. The total number of RGCs per retina ranged from 39,961±838 in CAST/EiJ to 53,872±1864 in 129X1/SvJ (p<0.005). Global BRN3A counts ranged from 34,572±494 in CAST/EiJ to 44,253±798 in C57BL/6J (p<0.005). SATB2 counts ranged from 9944±384 in BALB/cByJ to 15,872±1196 in CBA/CaJ (p<0.005). OPN4 density ranged from 110±7 cells/mm² in CAST/EiJ to 164±13 cells/mm² in 129X1/SvJ (p<0.05). Differences in SMI32 density were not significant across all strains, with densities ranging from 183±14 cells/mm² in A/J to 279±12 cells/mm² in C57BL/6J (not significant).</p><p><strong>Conclusions: </strong>There is a significant variation in total RGC counts and RGC subtypes across the different mouse strains. When working with different strains of mice, it is important to consider this strain-based variation before drawing conclusions from experimental data.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"120-129"},"PeriodicalIF":1.4,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691077","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":"RNA interference to reduce <i>Egr1</i> expression in rods delays retinal degeneration in a model of retinitis pigmentosa.","authors":"Luca Merolla, Antonia Fottner, Cornelia Imsand, Claudia Matter, Jessica Rowlan, Maureen Neitz, Larissa P Govers, Marijana Samardzija, Christian Grimm","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by progressive photoreceptor degeneration. The early growth response-1 gene (<i>Egr1</i>) is an immediate-early gene implicated in neurodegenerative and stress responses in the retina, among many other tissues. While its expression is induced in the retina across various RP models, its functional role in the degenerative process remains unclear. This study aimed to investigate the contribution of <i>Egr1</i> to photoreceptor degeneration in vivo.</p><p><strong>Methods: </strong>We used adeno-associated virus (AAV)-mediated RNA interference and transgenic overexpression to modify <i>Egr1</i> levels in rod and cone photoreceptors of wild-type and <i>Rho^P23H/+</i> mice. Rod- and cone-specific promoters enabled cell-specific expression. Exposure to high levels of white light was used to induce retinal degeneration in wild-type mice. We assessed retinal structure and transgene expression through funduscopy, optical coherence tomography (OCT), immunofluorescence, and histological analysis. We measured <i>Egr1</i> mRNA expression levels via real-time PCR and assessed the effects of <i>Egr1</i> modulation on the retina by determining the thickness of the outer nuclear layer (ONL) and the number of surviving cones.</p><p><strong>Results: </strong>Similar to other models of retinal degeneration, <i>Egr1</i> was induced in the retina after light exposure and in the <i>Rho^P23H/+</i> mouse during degeneration. AAV-mediated down- or upregulation of <i>Egr1</i> in rods or cones did not affect retinal morphology in wild-type mice. In <i>Rho^P23H/+</i> mice, <i>Egr1</i> knockdown in rods modestly preserved ONL thickness up to 12 weeks after AAV injection. Overexpression did not accelerate degeneration beyond controls. <i>Egr1</i> modulation in cones of wild-type or <i>Rho^P23H/+</i> mice did not affect cone survival.</p><p><strong>Conclusions: </strong><i>Egr1</i> upregulation is a consistent early marker of photoreceptor stress, independent of the nature of the underlying stimulus. Since moderate support for cell survival and preservation of retinal morphology was achieved through the downregulation of <i>Egr1</i> expression in rods, but not in cones of the <i>Rho^P23H/+</i> mouse, the function of EGR1 in degenerative processes may be cell type specific. Although <i>Egr1</i> may contribute to disease progression, it is unlikely to be a causative factor for degeneration. Our findings underscore the complexity of the transcriptional response in retinal degeneration and suggest that <i>Egr1</i> is a secondary effector of degenerative processes in rods.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"102-118"},"PeriodicalIF":1.4,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691042","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":"Nanobacterial detection in aqueous humor and its effect on postphacoemulsification visual acuity among highly myopic patients.","authors":"Xiaoli Wu, Yan Zhou, Fen Lan, Tao Li, Juan Tang, Guifang Wu, Xingde Liu","doi":"","DOIUrl":"","url":null,"abstract":"&lt;p&gt;&lt;p&gt;This study aimed to investigate factors affecting visual outcomes after phacoemulsification in highly myopic patients with cataracts, based on the detection of nanobacteria (NB) in aqueous humor. Fifty highly myopic patients with cataracts who underwent phacoemulsification surgery at The First People's Hospital of Ziyang from December 2022 to June 2023 were enrolled. Aqueous humor samples were gathered from patients before surgery, and NB were isolated and cultured from the aqueous humor. They were identified using scanning electron microscopy and transmission electron microscopy. The calcium-phosphorus ratios in NB cultures (NB group) and nanohydroxyapatite (nHA) cultures (nHA group) were determined by energy-dispersive X-ray spectroscopy. Cell inhibition was compared using a CCK-8 assay. The expressions of calcification-related proteins, bone morphogenetic protein 2, osteopontin, apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein in cells were examined by western blot. Based on the best-corrected visual acuity (VA) 3 months after surgery, patients were classified into a normal vision (NV) group (best-corrected VA ≥0.3) and an abnormal vision (AV) group (best-corrected VA &lt;0.3). The factors influencing postoperative VA and efficacy were analyzed. Results revealed that the characteristics of the aqueous humor cultures were consistent with the features of NB described in the literature, with NB measuring approximately 90 to 340 nm in transmission electron microscopy. Energy-dispersive X-ray results indicated no remarkable difference in calcium-phosphorus ratios between the NB and nHA groups (&lt;i&gt;p&lt;/i&gt; &gt; 0.05), but the NB group exhibited remarkably stronger cell inhibition relative to the nHA group (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Western blot results revealed obviously higher levels of bone morphogenetic protein 2, osteopontin, and Bcl-2-associated X proteins in the NB group compared to the nHA group (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), while Bcl-2 expression was sharply lower, with a great difference in the NB group (&lt;i&gt;p&lt;/i&gt; &gt; 0.05). The gap in best-corrected VA 1 month after surgery between the NV group (68%) and the AV group (32%) was obvious (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). With increasing recovery time, the number of patients with best-corrected VA ≥0.3 at 6 months postoperatively substantially increased (86%). The NB-positive rate in the aqueous humor samples was observably lower in the NV group than the rate in the AV group (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Univariate logistic regression analysis revealed great differences in age, duration of high myopia, axial length (AXL), corneal astigmatism, incidence of macular disease, and NB-positive rate (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Multivariate logistic regression analysis indicated that AXL and the presence of NB in the aqueous humor were independent factors influencing the postoperative visual prognosis of highly myopic patients with cataracts (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). The experimental results signified that NB cultures suppressed c","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"84-100"},"PeriodicalIF":1.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776784","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":"Insight into genes responsible for cornea plana, megalocornea, keratoconus and brittle cornea syndrome.","authors":"Di Zhu, Yuxi Zheng, Yi Jiang, Dongwei Guo, Yingwei Wang, Jiamin Ouyang, Zhen Yi, Shiqiang Li, Xiaoyun Jia, Xueshan Xiao, Wenmin Sun, J Fielding Hejtmancik, Qingjiong Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Inherited diseases characterized by abnormal corneal morphology include cornea plana, megalocornea, keratoconus and brittle cornea syndrome. This study aims to investigate genes responsible for these diseases.</p><p><strong>Methods: </strong>Variants in genes responsible for cornea plana, megalocornea, keratoconus and brittle cornea syndrome were analyzed and characterized by multistep bioinformatics approach based on three large data sets, including our in-house exome sequencing database from patients with inherited eye diseases, literature review, and gnomAD database. Additionally, the phenotypes of patients carrying these variants were collected.</p><p><strong>Results: </strong>125 variants in six genes, namely <i>KERA</i> (Keratocan; OMIM: 603288), <i>CHRDL1</i> (Chordin-like 1; OMIM: 300350), <i>VSX1</i> (Visual system homeobox 1; OMIM: 605020), <i>TUBA3D</i> (Tubulin, alpha-3d; OMIM: 617878), <i>ZNF469</i> (Zinc finger protein 469; OMIM: 612078), and <i>PRDM5</i> (PR domain-containing protein 5; OMIM: 614161), have been reported in 244 families by literature review, of which 78 with cornea plana, 38 with megalocornea, 67 with keratoconus, and 61 with brittle cornea syndrome. Three variants in <i>KERA</i> were identified in 2 families with cornea plana in our cohort. Moreover, all reported variants in <i>VSX1</i> were reclassified as likely benign or benign based on several major evidence, including high allelic frequency in gnomAD, presence in unaffected individuals in in-house data set, and relatively tolerated by multiple computational prediction tools. Misinterpreted variants in <i>VSX1</i> has been detected in up to 3.13% of the general population.</p><p><strong>Conclusions: </strong>This study delineates the genetic and clinical landscape of cornea plana, megalocornea, keratoconus and brittle cornea syndrome for the first time. The pathogenicity of <i>VSX1</i> variants could not be confirmed, making <i>VSX1</i> an unlikely candidate gene for keratoconus. Correct classification of genes like <i>VSX1</i> is critical in the era of genomic medicine.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"70-82"},"PeriodicalIF":1.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639280","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":"Review: The role of microglia in diabetic retinopathy and its potential as a therapeutic target.","authors":"Wen Liu, Jieyu Jiang, Wenwen Li, Zhiming Liu, Xiangdong Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a common and severe complication of diabetes, which poses a serious threat to vision, and its pathogenesis is complex. Inflammatory response plays a crucial role in the progression of DR, but currently, anti-vascular endothelial growth factor therapy, the preferred treatment for DR, only targets the vascular part. Therefore, determining a treatment method targeting the inflammatory response in DR is an important step in addressing DR. As immune cells within the retina, microglia play a key role in the inflammatory response in DR, which is a crucial link in its pathogenic mechanism. By regulating the inflammatory response of microglia, the progression of DR can be effectively slowed down. This review deeply explores the mechanism of action of microglia in DR by reviewing relevant research achievements and evaluates the potential of treatment strategies targeting microglia in slowing down the progression of DR. The study focuses on how to further optimize the treatment regimen for DR by regulating different pathways such as the release of inflammatory factors, the occurrence of oxidative stress, phenotypic transformation, intercellular interactions, and phagocytic activity of microglia, providing important clues for the development of novel treatment methods for DR. Through a comprehensive analysis and evaluation of the effectiveness and safety of these treatment strategies, the study aims to provide more precise and effective treatment regimens for patients with DR, so as to improve their visual prognosis and quality of life.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"49-68"},"PeriodicalIF":1.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639353","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":"Molecular responses of human retinal pigment epithelial cells to ebolavirus VP24.","authors":"Liam M Ashander, Yuefang Ma, Genevieve F Oliver, Binoy Appukuttan, Cameron D Haydinger, Steven Yeh, Glenn A Marsh, Justine R Smith","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Uveitis (inflammation inside the eye) is a disabling manifestation of the post-Ebola syndrome that affects 10% to 35% of individuals who survive the infection. Post-Ebola uveitis presents with diverse clinical features but frequently involves the posterior segment of the eye, where the retinal pigment epithelium plays a key role in directing immune responses. Our previous work shows that this epithelium is relatively susceptible to infection with <i>Zaire ebolavirus</i> (EBOV), the strain responsible for most Ebola outbreaks. In addition to production roles, viral proteins may act to alter the molecular responses of host cells.</p><p><strong>Methods: </strong>We investigated the activity of EBOV viral protein 24 (VP24) in human retinal pigment epithelial cells. An EBOV VP24 expression plasmid was constructed in-house. Multiple primary cell isolates were lipofectamine-transfected, first with VP24 or control expression plasmids and then with polyinosinic-polycytidylic acid (poly I:C) to simulate viral RNA. A type I interferon (IFN) response to transfection was confirmed by an IFN-β enzyme-linked immunosorbent assay. Cellular immune responses after 4- and 24-h exposures to poly I:C were characterized by reverse transcription-quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Multidimensional scaling, drawing on 19 immune response-related gene transcripts, covering antiviral, immunomodulatory, and proinflammatory molecules, demonstrated changes in gene expression profiles following transfection. Analysis of individual cell isolates showed a range of changes, including upregulation and downregulation of different gene transcripts across the two investigated time points.</p><p><strong>Conclusions: </strong>Our findings suggest VP24 elicits variable immune responses from human retinal pigment epithelial cells, potentially contributing to the variation in clinical presentations of uveitis in Ebola survivors.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"34-48"},"PeriodicalIF":1.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639314","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":"Submacular tissue repair and fibrosis in neovascular macular degeneration: A predictable outcome secondary to a chronic age-related endotheliopathy.","authors":"Beatriz G Armendariz, David Kent","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fibrosis is strictly a histopathological term that refers to the replacement of functional tissue with permanent deposition of nonfunctional extracellular matrix (ECM), following an injury or disease, and can occur in any tissue in the body. In this histological setting, there is no overt difference between fibrosis and scarring. However, in the clinical context, fibrosis tends to be associated with chronic disease, as it ensures ongoing ECM deposition. This could be considered \"excessive\" when compared to ECM deposition in acute or end-stage chronic disease. This perspective highlights how fibrosis in neovascular age-related macular degeneration follows a stereotypical tissue repair process similar to that seen in other tissues and how salient biologic processes, such as aging and metabolic health, impact fibrosis development. In addition, we highlight the emerging and pivotal profibrogenic role played by progressive endothelial cell (EC) dysfunction, together with secondary blood flow impedance in the neovasculature. This results in abnormal vascular permeability, endothelial-to-mesenchymal transition, and EC senescence-associated secretory phenotype, processes that could potentially be targeted therapeutically. Finally, the dramatic impact of anti-vascular endothelial growth factor therapy, by primarily targeting permeability of the nascent microvasculature, on the natural history of fibrosis in neovascular age-related macular degeneration indirectly highlights the potentially significant role of ECs in fibrosis development and points toward how novel future targeting of these cells could further modulate the development of fibrosis.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"22-32"},"PeriodicalIF":1.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639304","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":"Exploring the molecular basis of microphthalmia and anophthalmia: Insights from an Egyptian cohort.","authors":"Gehad Elmakkawy, Amira Nabil, Karim Nabil, Asmaa Kenawy Amin, David Maskill, Manir Ali, Daniel Schorderet, Nader Bayoumi, Nihal Shakankiri, Ebtesam Abdalla","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to gain insight into the molecular spectrum of anophthalmia and microphthalmia (A/M) in the Egyptian population.</p><p><strong>Methods: </strong>We studied a cohort of 34 patients from 31 unrelated families affected by the A/M spectrum. All patients underwent a thorough clinical examination, ophthalmological assessment, and genetic testing including conventional karyotyping and exome sequencing (ES).</p><p><strong>Results: </strong>Chromosomal anomalies were identified in six patients. ES was performed on the remaining cases, revealing potentially causative variants in 13 families. The implicated genes were <i>SOX2</i>, <i>OTX2</i>, <i>CHD7, HMX1, PRR12, ATOH7, ZBTB11, B3GALNT2, GCNT2</i>, <i>DPH1</i>, <i>GJA8, FRAS1</i> and <i>UBE3B</i>. Among the variants, six were classified as pathogenic, five as likely pathogenic, and two as variants of uncertain significance. Notably, a <i>DPH1</i> pathogenic variant was identified in a patient with bilateral severe microphthalmia, representing a novel phenotype. Additionally, we report the fifth family diagnosed with oculo-auricular syndrome.</p><p><strong>Conclusions: </strong>Our findings confirm that genetic factors are a predominant cause of both syndromic and non-syndromic A/M and underscore the value of ES in uncovering the molecular basis of this spectrum. By reporting novel variants and unusual phenotypes within our cohort, we contribute to expanding both the mutational landscape and the phenotypic spectrum of A/M associated syndromes.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"1-20"},"PeriodicalIF":1.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639311","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":"Reticular fiber distribution in sclera: Key to understanding pathologic myopia and posterior staphylomas.","authors":"Hirohiko Kakizaki, Heebae Ahn, Muhammad Abumanhal, Derrick Lian, Kan Ishijima, Hidenori Mito, Naoyuki Morishige","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the distribution of reticular fibers in the human sclera and explore their potential role in the pathogenesis of pathologic myopia and posterior staphyloma.</p><p><strong>Methods: </strong>Central sagittal sections of 13 globes (6 right eyes and 7 left eyes) were obtained from 12 East Asian cadavers aged 38-94 years (mean age: 74.9 years). Three scleral regions were examined: the pars plana, 3:00-3:30 clock-hour position, and 5:00-5:30 clock-hour position. Specimens were fixed in 10% formalin and stained with silver nitrate. ImageJ software was used for image processing and quantification of fiber density.</p><p><strong>Results: </strong>Reticular fiber density exhibited considerable inter- and intraindividual variability. The average densities at the pars plana, 3:00-3:30, and 5:00-5:30 were 31.07%, 26.10%, and 22.70%, respectively. Density ranges were 23.46%-58.51% (pars plana), 19.18%-43.07% (3:00-3:30), and 13.48%-50.95% (5:00-5:30). In 10 eyes, the pars plana showed the highest density, followed by 3:00-3:30 and then 5:00-5:30. Two eyes had the lowest density at 3:00-3:30, while one eye exhibited the highest density in this region.</p><p><strong>Conclusions: </strong>Reticular fiber density in the sclera exhibits considerable interindividual variability. Our findings suggest that regions of structural vulnerability within the sclera may extend beyond the posterior pole, potentially offering new insights into the pathogenesis of posterior staphyloma. A reduction in reticular fiber density may be implicated in the progression of pathologic myopia and the development of posterior staphylomas, although further investigation is warranted to substantiate this association.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"31 ","pages":"584-595"},"PeriodicalIF":1.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499520","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}