Molecular Vision最新文献

{"title":"Phenotypic variability observed in a Chinese patient cohort with biallelic variants in the <i>CLN</i> genes.","authors":"Xin Zhang, Ke Xu, Jie Shi, Yue Xie, Nien Li, Weiyu Yan, Zi-Bing Jin, Yang Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>The neuronal ceroid lipofuscinoses (NCLs) comprise a group of inherited neurodegenerative disorders with thirteen NCL-disease causing genes ceroid lipofuscinosis neuronal (<i>CLN)</i> identified. The purpose of this study was to describe the genetic and clinical characteristics of a cohort of Chinese patients harboring biallelic variants in the <i>CLN</i> genes.</p><p><strong>Methods: </strong>We recruited 14 patients from 13 unrelated families who carried biallelic variants in the <i>CLN</i> genes. All patients underwent ophthalmic and systematic evaluations, as well as comprehensive molecular genetic analyses. Reverse transcription polymerase chain reaction (RT-PCR) assays were performed to observe the effect of a novel non-canonical splice-site (NCSS) variant on <i>CLN3</i> pre-mRNA splicing. Eventually, eight patients were followed up.</p><p><strong>Results: </strong>We detected 21 variants in three <i>CLN</i> genes (<i>CLN3</i>, <i>MFSD8</i>, and <i>PPT1</i>); 13 variants were novel. RT-PCR assays indicated that the NCSS variant c.963-13A>G changed the pre-mRNA splicing, thereby creating an in-frame indel variant p.(W321delinsCPNLR) in <i>CLN3</i>. Diagnoses of neuronal ceroid lipofuscinosis (NCL) and non-syndromic retinal dystrophy (RD) were established in eight patients and six patients, respectively. The patients with NCL showed clinical heterogeneity, from typical phenotypes of CLN3 or CLN7 disease to juvenile- or adult-onset CLN1 disease. All patients experienced early and severe visual loss. A retinal evaluation revealed specific macular striation in 12 of the 14 patients.</p><p><strong>Conclusions: </strong>Patients with variants in the three <i>CLN</i> genes exhibit varied clinical spectra, which might be related to their genotype. All patients presented relatively unique retinal alterations. Our findings point to a crucial need for genetic analysis for the early and accurate diagnosis of patients with NCL.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"175-187"},"PeriodicalIF":1.8,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676215","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":"Uveal melanoma cell lines Mel270 and 92.1 exhibit a mesenchymal phenotype and sensitivity to the cytostatic effects of transforming growth factor beta in vitro.","authors":"Coralie Doudnikoff, Delphine Leclerc, Gaëlle Angenard, David Gilot, Cédric Coulouarn, Frederic Mouriaux","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Uveal melanoma (UM) is a deadly cancer with limited therapeutic options. At advanced stages, UM cells metastasize almost exclusively into the liver, where targeting metastatic UM cells remain a clinical challenge. Transforming growth factor beta (TGF-β) exhibits a functional duality in cancer, with one arm limiting tumor growth at an early stage and the second arm promoting metastasis at an advanced stage, notably by inducing an epithelial-to-mesenchymal transition. Thus, we hypothesized that targeting the TGF-β pathway could be relevant in the treatment of metastatic UM.</p><p><strong>Methods: </strong>In this study, we first characterized the pseudoepithelial/mesenchymal phenotype of UM cell lines Mel270 and 92.1. We then treated the cell lines with TGF-β to evaluate their responsiveness to the cytokine and to characterize the functional impact of TGF-β on their cell viability.</p><p><strong>Results: </strong>The results demonstrated, first, that the UM cell lines exhibited a mesenchymal phenotype and responded to TGF-β treatment in vitro and, second, that TGF-β promoted a cytostatic effect on the UM cell lines.</p><p><strong>Conclusions: </strong>Our findings indicate that UM cells are sensitive to the two arms of TGF-β signaling, which suggests that targeting the TGF-β pathway could be challenging in UM and would require a precise selection of patients in which only the prometastatic arm of TGF-β is activated.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"160-166"},"PeriodicalIF":2.2,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862002","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":"EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells.","authors":"Li Liu, Youde Jiang, Mohamed Al-Shabrawey, Xiaobai Ren, Sui Wang, Jena J Steinle","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To examine whether increased ephrin type-B receptor 1 (EphB1) leads to inflammatory mediators in retinal Müller cells.</p><p><strong>Methods: </strong>Diabetic human and mouse retinal samples were examined for EphB1 protein levels. Rat Müller cells (rMC-1) were grown in culture and treated with EphB1 siRNA or ephrin B1-Fc to explore inflammatory mediators in cells grown in high glucose. An EphB1 overexpression adeno-associated virus (AAV) was used to increase EphB1 in Müller cells in vivo. Ischemia/reperfusion (I/R) was performed on mice treated with the EphB1 overexpression AAV to explore the actions of EphB1 on retinal neuronal changes in vivo.</p><p><strong>Results: </strong>EphB1 protein levels were increased in diabetic human and mouse retinal samples. Knockdown of EphB1 reduced inflammatory mediator levels in Müller cells grown in high glucose. Ephrin B1-Fc increased inflammatory proteins in rMC-1 cells grown in normal and high glucose. Treatment of mice with I/R caused retinal thinning and loss of cell numbers in the ganglion cell layer. This was increased in mice exposed to I/R and treated with the EphB1 overexpressing AAVs.</p><p><strong>Conclusions: </strong>EphB1 is increased in the retinas of diabetic humans and mice and in high glucose-treated Müller cells. This increase leads to inflammatory proteins. EphB1 also enhanced retinal damage in response to I/R. Taken together, inhibition of EphB1 may offer a new therapeutic option for diabetic retinopathy.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"167-174"},"PeriodicalIF":2.2,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859329","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 effect of age on aqueous humor of humans with high myopia.","authors":"Kai Wen, Mengjun Fu, Yongtao Li, Haorun Zhang, Xiu Wang, Yang Cai, Yaoling Li, Ruihong Su, Yifang Huang, Ming Liu, Yufeng Zhang, Shaozhen Zhao, Jing Sun","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>High myopia is a common cause of vision loss. Age is an important factor in the development of high myopia. However, the effect of age on aqueous humor proteins in the context of high myopia is unknown. This study explored the effect of age on the aqueous humor protein of humans with high myopia.</p><p><strong>Methods: </strong>The aqueous humor of high myopia patients of different ages with implantable collamer lens implantation (ICL) was collected. Data-independent acquisition proteomic analysis was employed to explore differentially expressed proteins (DEPs). Two different bioinformatics analysis methods were used to interpret the proteomic results. Furthermore, three proteins were confirmed by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The study showed 18 upregulated and 20 downregulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the upregulated DEPs were highly enriched in coagulation and complement cascades. Weighted gene coexpression network analysis showed that the blue module was identified as a key module for high myopia and that the plasminogen (PLG) protein is a hub protein. ELISA confirmed that the expression levels of Alpha-1-antitrypsin were significantly upregulated in the aqueous humor of older patients presenting with high myopia.</p><p><strong>Conclusions: </strong>This is the first study to investigate the effect of age on the level of aqueous humor protein in high myopia. Our study provided a comprehensive data set on the overall protein changes of different ages of human high myopia, shedding light on its potential molecular mechanism in high myopia damage to the eyeball.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"137-149"},"PeriodicalIF":1.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391918","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":"Precise longitudinal monitoring of corneal change through in vivo confocal microscopy in a rat dry eye disease model.","authors":"Minjie Chen, Stefanie Seo, Xianni Simmons, Youssef Maroud, Trystin Wong, William Schubert, Samuel C Yiu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>While lacrimal gland removal is commonly used in animal models to replicate dry eye disease, research into systematically monitoring dry eye disease's longitudinal pathological changes is limited. In vivo confocal microscopy (Heidelberg Retina Tomograph 3 with a Rostock Cornea Module, Heidelberg Engineering Inc., Franklin, MA) can non-invasively reveal corneal histopathological structures. To monitor dry-eye-disease-related changes in corneal structures, we developed a precise monitoring method using in vivo confocal microscopy in a rat double lacrimal gland removal model.</p><p><strong>Methods: </strong>Five Sprague-Dawley rats (age 8-9 weeks, male) underwent double lacrimal gland removal. Modified Schirmer's tear test, blink tests, and in vivo confocal microscopy images were acquired pre-surgery and at 1, 2, and 4 weeks post-surgery. Three individual stromal nerves were selected per eye as guide images, and images of the corresponding sub-basal nerve plexus area were acquired via volume acquisition. The same area was re-imaged in subsequent weeks.</p><p><strong>Results: </strong>After double lacrimal gland removal, tear production was reduced by 60%, and the blink rate increased 10 times compared to pre-surgery. Starting from 1 week after surgery, in vivo confocal microscopy showed increased sub-basal nerve plexus nerve fiber density with inflammatory cell infiltration at the sub-basal nerve plexus layer and remained at an elevated level at 2 and 4 weeks post-surgery.</p><p><strong>Conclusions: </strong>We demonstrated that our precise monitoring method revealed detailed changes in the corneal nerves, the epithelium, and the stroma.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"150-159"},"PeriodicalIF":1.8,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792932","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 generation and characterization of a transgenic zebrafish line with lens-specific Cre expression.","authors":"Xuyan Peng, Xiaolin Jia, Guohui Shang, Mengjiao Xue, Mingjun Jiang, Dandan Chen, Fengyan Zhang, Yanzhong Hu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Danio rerio zebrafish constitute a popular model for studying lens development and congenital cataracts. However, the specific deletion of a gene with a Cre/LoxP system in the zebrafish lens is unavailable because of the lack of a lens-Cre-transgenic zebrafish. This study aimed to generate a transgenic zebrafish line in which Cre recombinase was specifically expressed in the lens.</p><p><strong>Methods: </strong>The pTol2 <i>cryaa</i>:Cre-polyA-<i>cryaa</i>:EGFP (enhanced green fluorescent protein) plasmid was constructed and co-injected with Tol2-transposase into one-to-two-cell-stage wild-type (WT) zebrafish embryos. Whole-mount in situ hybridization (ISH), tissue section, hematoxylin and eosin staining, a Western blot, a split-lamp observation, and a grid transmission assay were used to analyze the Cre expression, lens structure, and lens transparency of the transgenic zebrafish.</p><p><strong>Results: </strong>In this study, we generated a transgenic zebrafish line, zTg(<i>cryaa</i>:Cre-<i>cryaa</i>:EGFP), in which Cre recombinase and EGFP were driven by the lens-specific <i>cryaa</i> promoter. zTg(<i>cryaa</i>:Cre-<i>cryaa</i>:EGFP) began to express Cre and EGFP specifically in the lens at the 22 hpf stage, and this ectopic Cre could efficiently and specifically delete the red fluorescent protein (RFP) signal from the lens when zTg(<i>cryaa</i>:Cre-<i>cryaa</i>:EGFP) embryos were injected with the <i>loxP</i>-flanked RFP plasmid. The overexpression of Cre and EGFP did not impair zebrafish development or lens transparency. Accordingly, this zTg(<i>cryaa</i>:Cre-<i>cryaa</i>:EGFP) zebrafish line is a useful tool for gene editing, specifically with zebrafish lenses.</p><p><strong>Conclusions: </strong>We established a zTg(<i>cryaa</i>:Cre-<i>cryaa</i>:EGFP) zebrafish line that can specifically express an active Cre recombinase in lens tissues. This transgenic zebrafish line can be used as a tool to specifically manipulate a gene in zebrafish lenses.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"123-136"},"PeriodicalIF":2.2,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852229","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":"Conversion of Optineurin into an Hsp72-Inducible protein by C-terminal addition of green fluorescent protein.","authors":"Wool Suh, Seongsoo Sohn, Tae Eun Kim, Changwon Kee","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Optineurin is known to be associated with glaucoma. This protein has often been investigated as a form of fusion with green fluorescent protein (GFP), but there have been few reports describing any undesired effect of the tag on the normal expression of naïve optineurin. We investigated whether GFP tagging potentially does not influence the characteristics of optineurin expression.</p><p><strong>Methods: </strong>Wild-type and mutant (E50K and M98K) optineurins were fused with GFP or yellow fluorescent protein (YFP) either at their N-terminus or C-terminus. The fusion constructs were loaded onto an adenoviral vector and analyzed by western blot analysis and immunocytochemistry.</p><p><strong>Results: </strong>In human trabecular meshwork cells, optineurins fused to GFP at their C-terminus (OPTN-GFP) were prone to aggregation and did not fluoresce as brightly as their counterparts fused to YFP did regardless of whether they were wild-type or mutant forms. In addition, their expression was accompanied by the apparent induction of heat shock protein 72 (Hsp72). Furthermore, OPTN-GFP appears to interact with Hsp72 and be co-aggregated into vesicle-like structures scattered throughout the cytoplasm. However, optineurin fused to GFP at its N-terminus was not aggregate and did not induce Hsp72 expression.</p><p><strong>Conclusions: </strong>It is well-known that misfolded or unfolded proteins are prone to aggregation and, if they are fused with GFP, their chromophores are not fully fluorescent. Additionally, it is also well-known that heat shock response is a key cellular processes against the accumulation of misfolded or unfolded proteins. Therefore, our data suggest that the addition of GFP to the C-terminus of optineurin might convert it into an unfolded or partially folded protein.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"114-122"},"PeriodicalIF":1.8,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433379","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":"Microstructure of the corneal endothelial transition zone in different laboratory animals.","authors":"Jun Seob Lee, So Young Lee, Hee Seung Chin, Na Rae Kim, Ji Won Jung","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the microstructure of the corneal endothelial transition zone in different laboratory animals.</p><p><strong>Methods: </strong>Flat-mount corneas of rabbits, rats, and mice were stained with Alizarin Red S (ARS) and observed using scanning electron microscopy (SEM). The progenitor cell markers p75 neurotrophin receptor (p75NTR), SRY-box transcription factor 9 (SOX9), leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), telomerase reverse transcriptase (TERT), and proliferation marker K_i-67 were examined in the flat-mounted corneas of three laboratory animals using immunofluorescence microscopy.</p><p><strong>Results: </strong>On flat mounts, proximity to the trabecular meshwork correlated with weaker ARS staining and greater polymorphism of endothelial cells in the transition zone in all animals. On SEM, distinct and smooth structures of the transition zone were negligibly detected in all animals. The endothelial cells in the transition zone had irregular shapes, with less dense, less wavy intercellular junctions, especially in murine corneas, exhibiting unique intercellular cystic spaces. In the transition zone of the rabbit cornea, progenitor cell markers p75NTR, SOX9, Lgr5, TERT, and proliferation marker K_i-67 were expressed, in contrast to those in other murine corneas.</p><p><strong>Conclusions: </strong>Although the transition zone was not identified clearly, irregular cell morphology and loss of cell-cell contact were observed in all animal corneal endothelial cells. The proliferative capacity and the presence of progenitor cells were confirmed in the transition zone, especially in the rabbit cornea.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"107-113"},"PeriodicalIF":2.2,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859813","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":"Exosomal microRNAs as potential biomarkers and therapeutic targets in corneal diseases.","authors":"Swati Arora, Nagendra Verma","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Exosomes are a subtype of extracellular vesicle (EV) that are released and found in almost all body fluids. Exosomes consist of and carry a variety of bioactive molecules, including genetic information in the form of microRNAs (miRNAs). miRNA, a type of small non-coding RNA, plays a key role in regulating genes by suppressing their translation. miRNAs are often disrupted in the pathophysiology of different conditions, including eye disease. The stability and easy detectability of exosomal miRNAs in body fluids make them promising biomarkers for the diagnosis of different diseases. Additionally, due to the natural delivery capabilities of exosomes, they can be modified to transport therapeutic miRNAs to specific recipient cells. Most exosome research has primarily focused on cancer, so there is limited research highlighting the importance of exosomes in ocular biology, particularly in cornea-associated pathologies. This review provides an overview of the existing evidence regarding the primary functions of exosomal miRNAs and their potential role in diagnostic and therapeutic applications in the human cornea.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"92-106"},"PeriodicalIF":1.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867689","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: Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy.","authors":"Jacob H J Betts, Linda Troeberg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sorsby fundus dystrophy (SFD) is a rare, inherited form of macular degeneration caused by mutations in the gene encoding tissue inhibitor of metalloproteinases 3 (TIMP-3). There are 21 mutations currently associated with SFD, with some variants (e.g., Ser179Cys, Tyr191Cys, and Ser204Cys) having been studied much more than others. We review what is currently known about the identified SFD variants in terms of their dimerization, metalloproteinase inhibition, and impact on angiogenesis, with a focus on disparities between reports and areas requiring further study. We also explore the potential molecular mechanisms leading to the accumulation of extracellular TIMP-3 in SFD and consider how accumulated TIMP-3 causes macular damage. Recent reports have identified extraocular pathologies in a small number of SFD patients. We discuss these intriguing findings and consider the apparent discrepancy between the widespread expression of TIMP-3 and the primarily retinal manifestations of SFD. The potential benefits of novel experimental approaches (e.g., metabolomics and stem cell models) in terms of investigating SFD pathology are presented. The review thus highlights gaps in our current molecular understanding of SFD and suggests ways to support the development of novel therapies.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"30 ","pages":"74-91"},"PeriodicalIF":2.2,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852520","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}