Experimental eye research最新文献

{"title":"Constitutive and hypoxia-induced VEGF production by cultured uveal melanocytes and retinal pigment epithelial cells","authors":"Dan-Ning Hu ,&nbsp;Ruihua Zhang ,&nbsp;Codrin E. Iacob ,&nbsp;Andy Yao ,&nbsp;Shun-Fa Yang ,&nbsp;Chi- Chao Chan ,&nbsp;Richard B. Rosen","doi":"10.1016/j.exer.2025.110318","DOIUrl":"10.1016/j.exer.2025.110318","url":null,"abstract":"<div><div>Constitutive secretion of VEGF is crucial for maintaining ocular circulation while hypoxia-induced VEGF secretion plays an important role in pathological neovascularization. Previous studies have highlighted the critical function of RPE cells in these situations. The role of uveal melanocytes (UM) in VEGF production, however, has not been well described. The aim of this study was to compare VEGF production from human RPE and UM cell lines obtained in pairs from 3 donors to minimize individual variability in cellular function. Cells were subjected to hypoxia, (1% oxygen environment) or chemical hypoxia (cobalt chloride, CoCl₂) at different times or dosages, respectively. The effects of these treatments on the cell viability and cell proliferation were tested using MTT and cell counting with trypan blue testing. The production of VEGF and its main upstream factor (hypoxia-inducible factors-1α, HIF-1α) were measured in the conditioned culture medium and cellular extracts, by using ELISA analysis. Additionally, mRNA levels of VEGF and HIF-1α were quantified through real-time PCR analysis. The effects of CoCl₂ on the expression of VEGF and HIF-1α in UM and RPE cells were also examined using flow cytometry. Hypoxia and COCL₂ exposure did not affect cell viability and cell proliferation. This study revealed that the constitutive production of VEGF by RPE cells is significantly greater than from the UM. However, UM demonstrated a more robust response to high hypoxia or chemical hypoxic stimulation compared to RPE cells. The data suggests that while RPE cells play a critical role in constitutive VEGF production under normal conditions, UM may contribute significantly to the pathological increase in VEGF under severe ocular hypoxia. The observation that intraocular injection of CoCl₂ to produce local chemical hypoxia, results in a significant increase of VEGF levels in intraocular fluids and tissues, has not been reported previously. While this model cannot currently test the <em>in vitro</em> results, it may help further our understanding of UM and RPE cells' roles in VEGF production in future studies using more advanced technologies in a well-established <em>in vivo</em> model.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110318"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-106a regulates the apoptosis and oxidative stress of porcine trabecular meshwork cells by targeting FAS","authors":"Junyi Lai ,&nbsp;Chen Tan ,&nbsp;Yunsheng Qiao ,&nbsp;Xinghuai Sun ,&nbsp;Junyi Chen","doi":"10.1016/j.exer.2025.110313","DOIUrl":"10.1016/j.exer.2025.110313","url":null,"abstract":"<div><div>This study investigates the impact of miR-106a on trabecular meshwork (TM) and its potential molecular mechanism, as TM dysfunction due to decreased cell viability is a major pathological feature of POAG. Primary porcine TM (PTM) cells were isolated and exposed to hyperoxic conditions to induce senescence. Through small RNA sequencing and qPCR verification, miR-106a was downregulated in aging PTM cells. The transfection system overexpressing miR-106a in PTM cells was achieved by polydopamine (PDA)/polyethyleneimine (PEI) nanoparticles (PDA/PEI NPs). Proliferation, apoptosis, and antioxidant capacity of PTM cells under normal and H₂O₂-treated conditions were assessed using CCK-8, mitochondrial assays, and reactive oxygen species measurements. As a result, Overexpression of miR-106a boosted PTM cell proliferation, dampened apoptosis, and enhanced capacity of antioxidative stress. Western blots were carried out to detect the expression of target genes of miR-106a. Mechanically, the expression of the two predicted target genes, FAS and CASP10, and genes of FAS-mediated signaling pathway were suppressed under normal and oxidative stress conditions. Dual-luciferase reporter results confirmed a direct binding between miR-106a and FAS. Thus, miR-106a promotes PTM cells’ viability, suppresses apoptosis and enhances antioxidative stress capacity by targeting FAS in PTM cells. Therefore, our study provides a potential therapeutic target in glaucoma.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110313"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic mutation in HSF4 is associated with retinal degeneration in mice","authors":"Baixue Liu ,&nbsp;Youfei Lang ,&nbsp;Yujie Li ,&nbsp;MingJun Jiang ,&nbsp;Mengjiao Xue ,&nbsp;Xiaolin Jia ,&nbsp;Xuyan Peng ,&nbsp;Yanzhong Hu","doi":"10.1016/j.exer.2025.110316","DOIUrl":"10.1016/j.exer.2025.110316","url":null,"abstract":"<div><div>Genetic mutations in Hsf4 cause developmental defect of lens at postnatal age. However, the regulatory effect of Hsf4 mutations on retinal homeostasis have not been elucidated. Here we found that HSF4 expresses in retinal and its expression level decrease with age increase. Using Hsf4^del mice, which express a Hsf4 mutant with deletion of 42 amino acids in-frame- in the N-terminal hydrophobic region and develop cataracts at P27, we found that Hsf4^del mutation downregulated the expression of visual cycle regulatory proteins, RPE65, RDH5 and RLBP1 and heat shock proteins HSP25 and HSP90, but upregulated retinal gliosis and senescence-associated proteins such as cycle-inhibitors P21 and P16 in P10 retina without change retinal structure. With age increase Hsf4^del mice undergo retinal degeneration, characterized by thinner ONL, disorganized INL, disconnected RPE, neovascularization, and lipofuscin deposits. ERG results showed that the amplitudes of a- and b-waves at dark adaption were reduced in Hsf4^del mice at P15, worsening with age. Intravitreal injection of AAV-Flag-Hsf4b in one-month-old Hsf4^del mice partially restored the expression of visual cycle proteins and ERG responses and reduced the gliosis. Studies in vitro indicated that Hsf4 is able to bind to promoters of RPE65 and RDH5. Altogether, these data suggest that Hsf4 participates in regulating the expression of retinal visual cycle-regulatory proteins in addition to heat shock proteins during early retinal development. Genetic mutations in Hsf4 is associated with not only congenital cataracts but also retinal degeneration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110316"},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDZK1 regulated by miR-145-5p protects against endothelial cell apoptosis and diabetic retinopathy by targeting mitochondrial function","authors":"Meixia An ,&nbsp;Jialuo Huang ,&nbsp;Jian Zhao ,&nbsp;Lili Wang ,&nbsp;Yanli Liu","doi":"10.1016/j.exer.2025.110314","DOIUrl":"10.1016/j.exer.2025.110314","url":null,"abstract":"<div><div>Mitochondria are a focus of biomedical research because of their role in apoptosis and diabetic retinopathy (DR) initiation and progression. However, the detailed mechanisms underlying mitochondrial disorders and endothelial dysfunction during DR remain elusive. We identified PDZ domain containing 1 (PDZK1) as a key factor linking endothelial mitochondrial dysfunction and cell apoptosis during DR progression. PDZK1 was downregulated by high concentrations of glucose in human retinal capillary endothelial cells (HRCECs) and decreased in serum from patients with DR. PDZK1 knockout induced endothelial cell apoptosis and an irregular and disordered arrangement of retinal cells, aggravating DR. Moreover, PDZK1 loss impaired endothelial mitochondrial function with accumulated damaged mitochondria, decreased mitochondrial DNA (mtDNA) content, and increased reactive oxygen species (ROS) production. Mechanistically, mRNA sequencing showed that PDZK1 deficiency in endothelial cells interfered with mitochondrial function by increasing ATF4 (Activating Transcription Factor 4) expression. Further studies showed that PDZK1 was inhibited by miR-145-5p. The expression of miR-145-5p was significantly upregulated in the serum of patients with DR and HRCECs with high glucose concentration, leading to endothelial dysfunction and DR progression. Our results suggested that PDZK1 deficiency is crucial in mediating retinal endothelial cell apoptosis and is associated with mitochondrial dysfunction. PDZK1 overexpression by upstream miRNA, or its downstream molecule, ATF4, may represent novel therapeutic approaches for DR treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110314"},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics unveils the role of pipecolic acid in regulating monocytes/macrophages-endothelial cells crosstalk to modulate choroidal neovascularization","authors":"Chang Liu ,&nbsp;Fangcheng Xu ,&nbsp;Ruoyan Wei ,&nbsp;Yun Cheng ,&nbsp;Yunzhe Wang ,&nbsp;Yefei Shi ,&nbsp;Ke Yang ,&nbsp;Wenhui Peng ,&nbsp;Weixia Jian ,&nbsp;Haixiang Wu ,&nbsp;Meiyan Li","doi":"10.1016/j.exer.2025.110315","DOIUrl":"10.1016/j.exer.2025.110315","url":null,"abstract":"<div><div>Choroidal neovascularization (CNV) is a leading cause of vision loss in ocular diseases, including age-related macular degeneration (AMD). Despite extensive research, the underlying mechanisms of CNV remain incompletely understood, with a predominant focus on endothelial dysfunction. CNV, however, is a multi-cellular, multi-stage process involving complex interactions between endothelial cells, monocytes/macrophages, and other immune cells. In this study, we employed a dual-platform metabolomics approach combining liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to identify key metabolic alterations associated with CNV. Our results revealed significant changes in metabolic pathways during CNV progression. Using a myeloid lineage tracing mouse model, we further explored how Pipecolic acid regulates interactions between monocytes/macrophages and endothelial cells, key players in CNV development. We found that Pipecolic acid modulates monocyte/macrophage-endothelial cell crosstalk, inhibiting pathological angiogenesis. These results provide valuable insights into the molecular mechanisms driving CNV and highlight potential therapeutic targets for treating ocular neovascular diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110315"},"PeriodicalIF":3.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slope Chain Code-based scale-independent tortuosity measurement on retinal vessels.","authors":"Zian Fanti, Ulf-Dietrich Braumann, Franziska G Rauscher, Thomas Ebert, Ernesto Bribiesca, M Elena Martinez-Perez","doi":"10.1016/j.exer.2025.110286","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110286","url":null,"abstract":"<p><p>Retinal vascular tortuosity presents valuable potential as a clinical biomarker for many relevant vascular and systemic diseases. Our work exhibits twofold: first, the definition of a novel scale-invariant metric to measure retinal blood vessel tortuosity; and second, the generation of a local database, called SCALE-TORT, with the intention of providing a means to test the scale invariance property on real retinal vessels rather than on synthetic data. The proposed scale invariant tortuosity metric is based on the Extended Slope Chain Code which uses variable straight-line segments for describing curves. It is focused on the representation of high-definition curves, the length of the segments is a function of the slope changes of the curve. Scale invariance is an important property when several different retinal image settings or different acquisition sources are used during a particular study or in clinical practice. The database SCALE-TORT, introduced herein, was built semi-automatically from digital images containing the coordinates of blood vessel central lines (curves) taken from images of the same eye obtained by two different imaging methodologies: retinal fundus camera and scanning laser ophthalmoscope. The vessel curves extracted from the same eye are paired for images acquired by the fundus camera and those acquired by the scanning laser ophthalmoscope to evaluate the scale invariance of the metric. Ten different tortuosity metrics were implemented and compared including our proposed metric. Three experiments were conducted to test the metrics and their properties. The first aimed to determine which tortuosity metrics possess the following properties: scale invariance, sensitivity to sudden tortuosity changes when the curve remains constant in size, and how they behave when curves are concatenated. In the second experiment, all reviewed metrics were tested on the publicly available RET-TORT database, to compare the results of the specific metric with the tortuosity classification provided by their experts and in comparison with other authors. Finally, in the third experiment, the behavior of different metrics, including those which are scale-invariant, were tested by utilizing the paired retinal vessel curves from our new SCALE-TORT database. In comparison with other tortuosity metrics, we show that the metric Extended Slope Chain Code proposed in this work optimally complies with scale invariance, in addition to having sufficient sensitivity to detect abrupt changes in tortuosity. Easy implementation being a further plus. Furthermore, we present a new and valueable database for scale property evaluation on images of retinal blood vessels called SCALE-TORT. As far as we are aware, there is no public database with these characteristics.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110286"},"PeriodicalIF":3.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Features that distinguish age-related macular degeneration from aging","authors":"Dorota Skowronska-Krawczyk ,&nbsp;Silvia C. Finnemann ,&nbsp;Maria B. Grant ,&nbsp;Katherine Held ,&nbsp;Zhengping Hu ,&nbsp;Yuancheng Ryan Lu ,&nbsp;Goldis Malek ,&nbsp;Florian Sennlaub ,&nbsp;Janet Sparrow ,&nbsp;Patricia A. D'Amore","doi":"10.1016/j.exer.2025.110303","DOIUrl":"10.1016/j.exer.2025.110303","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging changes and those observed in AMD. We provide a unique perspective on how genetic and environmental components modulate aging in the eye, as well as the specific role of the aging RPE and retina in the pathogenesis of AMD. Topics discussed include the mechanism of aging and its relation to the mechanism of AMD, current animal models that can be used to recapitulate some aspects of the pathology, and potential interventions that shift the balance towards healthy aging and therefore attenuate, prevent or delay the initiation of the disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110303"},"PeriodicalIF":3.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-224-3p regulates ferroptosis and inflammation in lens epithelial cells by targeting ACSL4","authors":"Feng Sun ,&nbsp;Na Li ,&nbsp;Yan Liu,&nbsp;Yuanyuan Han,&nbsp;Mengyue Xu,&nbsp;Che Xu,&nbsp;Juan Li,&nbsp;Jianfeng Wang","doi":"10.1016/j.exer.2025.110306","DOIUrl":"10.1016/j.exer.2025.110306","url":null,"abstract":"<div><div>In this study, we investigated the expression levels of miR-224-3p and inflammatory factors in the lens epithelium of patients with high myopia cataract (HMC) to determine how miR-224-3p/ACSL4 affects ferroptosis and inflammation in human lens epithelial cells (HLECs). The capsule tissues (including lens epithelial cells) of 36 patients with HMC and 36 patients with age-related cataract (ARC) were taken respectively. 18HMC and 18ARC capsule tissues were selected for RNA sequencing (RNA-Seq) and the rest were used for qPCR assays. The expression of miR-224-3p and ACSL4 in the capsules of patients was detected by qPCR, and RNA was extracted from each of the six capsules. To evaluate ferroptosis and inflammation, the levels of expression of ACSL4, GPX4, TFR1 and IL-6 was determined by immunohistochemistry, Transmission electron microscopy image showed the structure of mitochondria. The differential expression of mir-224-3p was identified through RNA sequencing, with its expression significantly increased in HMC. As a result, mir-224-3p was chosen for further experimentation. The expression levels of ACSL4, TFR1 and GPX4 varied between HMC and ARC. Target Scan predicted a direct binding site between mir-224-3p and ACSL4. The results showed that the expression levels of miR-224-3p, TFR1 and IL-6 in the HMC patients were significantly greater than those in ARC. ACSL4 and GPX4 in HMC were considerably lower than those in ARC. Electron microscopy images revealed that the mitochondria of HMC were significantly shrunken compared to those of ARC. So it was thought that ferroptosis and inflammation occured in HMC patients. A dual-luciferase report found miR-224-3p regulated ACSL4. PCR and WB assays revealed that ACSL4 was the downstream target gene of miR-224-3p. We also found that miR-224-3p promoted the proliferation and migration of HLECs. TNF-α (20 ng/mL) induced an inflammatory response in HLECs. Also, miR-224-3p effectively inhibited ferroptosis in HLECs induced by erastin, meanwhile the expression levels of Fe2+, MDA, ROS, and TFR1 were reduced, while GPX4 and GSH expression levels were elevated. The level of expression of IL-6 was decreased. Additionally, miR-224-3p increased the viability of HLECs by regulating ferroptosis and inflammation via ACSL4 targeting.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110306"},"PeriodicalIF":3.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal degeneration increases inter-trial variabilities of light-evoked spiking activities in ganglion cells","authors":"Da Eun Kim ,&nbsp;Sein Kim ,&nbsp;Minju Kim ,&nbsp;Byoung-Kyong Min ,&nbsp;Maesoon Im","doi":"10.1016/j.exer.2025.110305","DOIUrl":"10.1016/j.exer.2025.110305","url":null,"abstract":"<div><div>Retinal ganglion cells (RGCs) transmit visual information to the brain in the form of spike trains, which form visual perception. The reliabilities of spike timing and count are thought to play a crucial role in generating stable percepts. However, the effect of retinal degeneration on spike reproducibility remains underexplored. In this study, we examined longitudinal changes of both spike timing and count across different RGC types in response to repeated presentations of an identical light stimulus in retinal degeneration 10 (<em>rd10</em>) mice (B6.CXBl-<em>Pde6b</em>^rd10/J), a well-established model of retinitis pigmentosa (RP).</div><div>We recorded the spiking responses of RGC populations to repeated white flashes using 256-channel multi-electrode array (MEA) at four <em>rd10</em> age groups representing various stages of retinal degeneration. Our experimental results revealed a significant reduction in both spike timing and count consistencies compared to those in wild-type RGC recordings. Furthermore, the inter-trial variability patterns of different RGC types were found to differ throughout the degeneration process. For instance, when the spike time tiling coefficient (STTC) was used to evaluate inter-trial spike timing consistency, contrast-sensitive RGCs (ON, OFF, and ON-OFF types) exhibited a systematic decrease in spike timing consistency as degeneration progressed, whereas the remaining units did not show similar trends. Thus, we concluded that light-evoked spike trains become less consistent as degeneration progresses, with variability in spike timing and spike count varying across cell types.</div><div>Given the critical role of spiking reliability in visual perception, our findings highlight the importance of accounting for cell type-specific degeneration patterns and inter-trial spiking inconsistencies when developing visual rehabilitation therapies to achieve enhanced performance. The underlying mechanism(s) driving the inter-trial spiking inconsistencies warrant further investigation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110305"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel progressive rod-cone degeneration mutation causes retinitis pigmentosa","authors":"Xiaoliao Peng ,&nbsp;Xuejun Wang ,&nbsp;Yuliang Wang ,&nbsp;Weijung Ten ,&nbsp;Qinghong Lin ,&nbsp;Xingtao Zhou","doi":"10.1016/j.exer.2025.110276","DOIUrl":"10.1016/j.exer.2025.110276","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) is a genetic disorder often caused by single or multiple mutations. The progressive rod-cone degeneration (<em>PRCD</em>) gene is linked to retinal degeneration. This study identified a family affected by RP carrying a frameshift mutation (c.67del) in the <em>PRCD</em> gene. Blood samples from a patient with RP and three family members were analyzed by whole-exome sequencing. A point-mutant mouse model was created using gene-targeted modification to validate the suspected causative gene phenotypically. Binocular ophthalmological exams, including electroretinography and optical coherence tomography (OCT), were performed at P0, P30, P60, and P180. After 180 days, retinas were analyzed by polymerase chain reaction (PCR), Western blotting (WB) and immunofluorescence to measure gene expression and observe phenotypical changes, respectively. We used whole-exome sequencing of peripheral blood to identify a novel frameshift mutation in the <em>PRCD</em> gene: c.67del (p.Val23SerfsTer31). This mutation introduces a premature termination codon at amino acid position 31. Predictive tools indicate that this mutation is likely pathogenic. The proband's parents are consanguineous; the mother is a heterozygous carrier; the remaining two living family members exhibit a wild-type genotype. PCR, WB and immunofluorescent staining revealed significantly low <em>Prcd</em> expression in the <em>Prcd</em>^−/− mice than in wild-type mice. OCT and visual electrophysiological assessments detected lesions in the fundus of <em>Prcd</em>^−/− mice eyes; the severity of pathological changes increased with age. This study discovered a new mutation in the RP-associated <em>Prcd</em> gene and confirmed that it causes retinopathy in Prcd^−/− mice.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110276"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}