Experimental eye research最新文献

{"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 ,&nbsp;Ulf-Dietrich Braumann ,&nbsp;Franziska G. Rauscher ,&nbsp;Thomas Ebert ,&nbsp;Ernesto Bribiesca ,&nbsp;M. Elena Martinez-Perez","doi":"10.1016/j.exer.2025.110286","DOIUrl":"10.1016/j.exer.2025.110286","url":null,"abstract":"<div><div>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 valuable 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.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 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":"OA","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}

{"title":"Dissecting the biological complexity of age-related macular degeneration: Is it one disease, multiple separate diseases, or a spectrum?","authors":"Jason M.L. Miller ,&nbsp;Benjamin R. Thompson ,&nbsp;James T. Handa ,&nbsp;Philip Luthert ,&nbsp;Usha Chakravarthy ,&nbsp;Karl G. Csaky ,&nbsp;Alan Bird ,&nbsp;Benjamin K. Young ,&nbsp;Sudha K. Iyengar ,&nbsp;Jiwon Baek ,&nbsp;Moussa A. Zouache ,&nbsp;Burt T. Richards ,&nbsp;Gregory S. Hageman ,&nbsp;Gerry Rodrigues ,&nbsp;Kapil Bharti ,&nbsp;John G. Flannery ,&nbsp;Michael B. Gorin ,&nbsp;Catherine Bowes Rickman","doi":"10.1016/j.exer.2025.110304","DOIUrl":"10.1016/j.exer.2025.110304","url":null,"abstract":"<div><div>Clinicians recognize the heterogeneity of age-related macular degeneration (AMD) in presentation, progression, and treatment response, as well as the challenges in distinguishing it from other macular degenerations. As part of the 2024 Ryan Initiative for Macular Research meeting, a group of clinician-scientists and basic scientists were convened to consider the question of whether AMD should be classified as a single disorder or a spectrum of conditions. To answer this question, we reviewed research on several “dimensions” that constitute AMD risk or pathogenesis: genetics, ancestry, retinal imaging findings, diet and environment, aging, and outer retinal molecular and cellular pathways. The group reached a consensus that AMD represents a heterogeneous collection of disease states arising from the interplay of these dimensions. This heterogeneity can be conceived of as a “cloud” of AMD phenotypes. Defining subtypes within this “cloud” requires longitudinal cohorts of well-genotyped and phenotyped patients who progress from no AMD through late AMD, analyzed by unsupervised learning. Comparing the AMD subtypes that emerge from this analysis, especially -omics data from each subtype, will illuminate biology that is applicable to certain subtypes of AMD patients and molecular pathogenic mechanisms that universally apply to all AMD. This knowledge will, in turn, drive improved drug development.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110304"},"PeriodicalIF":3.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472338","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":"Cultivation and characterization of oral mucosal epithelial cells on fibrin gel in a xenobiotic-free medium for the treatment of limbal stem cell deficiency","authors":"Joao Victor Cabral ,&nbsp;Eleni Voukali ,&nbsp;Natalie Smorodinova ,&nbsp;Lukas Balogh ,&nbsp;Vojtech Kolin ,&nbsp;Pavel Studeny ,&nbsp;Magdalena Netukova ,&nbsp;Katerina Jirsova","doi":"10.1016/j.exer.2025.110300","DOIUrl":"10.1016/j.exer.2025.110300","url":null,"abstract":"<div><div>For the treatment of bilateral limbal stem cell deficiency (LSCD), cell therapy with transplantation of cultivated oral mucosa epithelial cells (COMET) is a promising alternative. Although not yet established, current protocols on the cultivation of oral mucosal epithelial cell (OMECs) sheets are based mainly on substrates and xenobiotic additives that may lead to variable outcomes and undesirable immune responses by the patient. The aim of this study was to characterize OMECs cultivated in xenobiotic-free media (XF) seeded on fibrin gel, in comparison to conventional complex (COM) medium. Oral mucosal biopsies were retrieved from 31 donors. After cultivation in COM or XF medium, OMECs were compared based on growth kinetics, morphology, cell size and viability. Using immunofluorescence and gene expression analyses, the degree of stemness, proliferation and differentiation was evaluated in OMEC cultures. Our findings showed that although OMECs showed a similar morphology and viability, and comparable growth kinetics, immunofluorescence revealed the preservation of stemness (p63 + p40 positivity in cells ≤11 μm) and proliferation in both COM and XF. Gene expression analyses showed that keratin (K)13 and K15 expression levels were significantly higher in XF (adj. <em>p</em> &lt; 0.001), but otherwise COM and XF-treated OMECs had comparable transcriptional profiles in a panel of stemness, proliferation and differentiation genes. These results demonstrate the feasibility of culturing OMECs on fibrin gel without xenogeneic additives, while maintaining their undifferentiated state and preserving stemness. In conclusion, both in terms of results and methodology, the procedures presented here are suitable for implementation in clinical practice.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110300"},"PeriodicalIF":3.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467477","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-214-3p attenuates ferroptosis-induced cellular damage in a mouse model of diabetic retinopathy through the p53/SLC7A11/GPX4 axis","authors":"Fang Yuan ,&nbsp;Songyu Han ,&nbsp;Yahong Li ,&nbsp;Sanming Li ,&nbsp;Dian Li ,&nbsp;Qingjun Tian ,&nbsp;Ronghua Feng ,&nbsp;Ying Shao ,&nbsp;Xing Liang ,&nbsp;Jingbo Wang ,&nbsp;Hetian Lei ,&nbsp;Xiaorong Li ,&nbsp;Yajian Duan","doi":"10.1016/j.exer.2025.110299","DOIUrl":"10.1016/j.exer.2025.110299","url":null,"abstract":"<div><div>Ferroptosis has been implicated in the development of diabetic retinopathy (DR). This study aimed to identify novel ferroptosis-related regulators involved in the pathophysiology of DR using an in vivo streptozotocin (STZ)-induced diabetic model in C57BL/6J mice and cultured primary human retinal vascular endothelial cells (HRECs). Transmission electron microscopy revealed mitochondrial morphological changes consistent with ferroptosis in vascular endothelial cells from STZ-treated mice. Western blot analysis showed increased levels of ferroptosis markers (4-HNE, p53, phosphorylated p53) along with decreased levels of glutathione (GSH), SLC7A11, and GPX4 in diabetic mice. <em>In vitro</em> experiments demonstrated that ferroptosis inhibitors, including pifithrin-α (a p53 inhibitor) and ferrostatin-1 (Fer-1), mitigated cellular damage and Fe²⁺ accumulation in high-glucose-treated HRECs. These inhibitors also improved mitochondrial membrane potential and restored GSH levels. Bioinformatics analysis and dual-luciferase assays identified a p53 binding site within the miR-214-3p sequence. Overexpression of miR-214-3p in high-glucose-treated HRECs resulted in downregulation of p53 and upregulation of SLC7A11 and GPX4, thereby alleviating ferroptosis-induced injury. This study demonstrates that ferroptosis contributes to retinal damage at tissue, cellular, and molecular levels in DR. Specifically, p53, regulated by miR-214-3p, promotes ferroptosis through the SLC7A11/GPX4 pathway under high-glucose conditions. These findings suggest that the miR-214-3p/p53/SLC7A11/GPX4 axis could serve as a potential therapeutic target for managing ferroptosis and retinal damage in diabetic retinopathy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110299"},"PeriodicalIF":3.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465378","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}