Experimental eye research最新文献

{"title":"Increased glucose concentration modifies TGF-β1 and NFκB signaling pathways in aniridia limbal fibroblasts, in vitro","authors":"Zhen Li ,&nbsp;Tanja Stachon ,&nbsp;Sabrina Häcker ,&nbsp;Fabian N. Fries ,&nbsp;Ning Chai ,&nbsp;Berthold Seitz ,&nbsp;Lei Shi ,&nbsp;Shao-Lun Hsu ,&nbsp;Shuailin Li ,&nbsp;Shanhe Liu ,&nbsp;Maryam Amini ,&nbsp;Shweta Suiwal ,&nbsp;Nóra Szentmáry","doi":"10.1016/j.exer.2024.110163","DOIUrl":"10.1016/j.exer.2024.110163","url":null,"abstract":"<div><div>To determine the impact of increased glucose concentration on gene expression of primary healthy human limbal fibroblasts (LFCs) and congenital aniridia human limbal fibroblasts (AN-LFCs), <em>in vitro</em>.</div><div>LFCs (n = 8) and AN-LFCs (n = 8) were isolated and cultured in serum containing DMEM, including either normal glucose (17.5 mM) or increased glucose (70 mM) concentration for 48h or 72h, respectively<strong>.</strong> mRNA and protein expression of transforming growth factor beta 1 (TGF-β1), alpha-smooth muscle actin (ACTA)2A1, SMAD 2/3, hypoxia markers such as nuclear factor kappa B (NFκB), inducible nitric oxide synthase (iNOS), hypoxia-inducible factor 1-alpha (HIF-1ɑ), oxidative stress markers such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Catalase (CAT) were analyzed using qPCR and Western blot.</div><div>In 70 mM glucose concentration medium for 48 h, <em>TGF-β1</em> mRNA expression was significantly lower (p = 0.001, p &lt; 0.001), <em>Nrf2</em> (p = 0.001, p = 0.001) and <em>CAT</em> (p = 0.001, p = 0.001) mRNA expression was significantly higher in LFCs and AN-LFCs, than using 17.5 mM glucose concentration medium. In addition, in 70 mM glucose concentration medium for 48 h, <em>SMAD 2</em>, <em>SMAD 3</em>, <em>NFκB</em>, <em>HIF-1ɑ</em> mRNA expression was significantly lower in AN-LFCs, than in 17.5 mM glucose concentration medium (p = 0.003, p = 0.002, p = 0.008, p = 0.020). At this time-point in 70 mM glucose concentration medium, at protein level, TGF-β1, SMAD2/3 and NFκB were significantly lower in AN-LFCs, than in 17.5 mM glucose concentration medium (p = 0.041, p = 0.002, p = 0.012).</div><div>In 70 mM glucose concentration medium for 72h, <em>TGF-β1</em> was significantly higher (p &lt; 0.001, p &lt; 0.001) and <em>Nrf2</em> (p = 0.001, p = 0.001) and <em>CAT</em> (p &lt; 0.001, p &lt; 0.001) mRNA were significantly lower in LFCs and AN-LFCs, than in 17.5 mM glucose concentration medium. At this time-point, in 70 mM glucose concentration medium, <em>NFκB</em> mRNA was significantly higher (p &lt; 0.001) in LFCs<strong>,</strong> than in 17.5 mM glucose concentration DMEM medium. In 70 mM glucose concentration medium for 72 h, TGF-β1 and NFκB protein were significantly lower in AN-LFCs, than in 17.5 mM glucose concentration medium (p &lt; 0.001, p &lt; 0.001).</div><div>Our study confirmed that high glucose concentration has an impact on TGF-β1 and NFκB signaling both in AN-LFCs and LFCs. These findings highlight that prolonged exposure to high glucose levels may contribute to cellular stress and dysfunction in LFCs and AN-LFCs.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110163"},"PeriodicalIF":3.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692848","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":"Macromolecular crowding agent dependent extracellular matrix deposition and growth factor retention in human corneal fibroblast cultures","authors":"Mehmet Gurdal,&nbsp;Dimitrios I. Zeugolis","doi":"10.1016/j.exer.2024.110162","DOIUrl":"10.1016/j.exer.2024.110162","url":null,"abstract":"<div><div>The major obstacle in the commercialisation and clinical translation of tissue engineered medicines is the required for the development of implantable tissue surrogates prolonged <em>in vitro</em> culture. Macromolecular crowding (MMC) enhances and accelerates extracellular matrix (ECM) deposition, thus offering an opportunity to bridge the gap between research and development in tissue engineered substitutes. However, the optimal MMC agent is still elusive. Herein, we first assessed the biophysical properties of the most widely used MMC agents [κλ carrageenan (κλ CR), λ carrageenan (λ CR) and Ficoll™ cocktail (FC)] and then assessed their effect in basic cell function, ECM deposition and growth factor retention in human corneal fibroblast (hCF) cultures. Dynamic light scattering analysis revealed that both CR macromolecules had significantly lower and higher zeta potential and hydrodynamic radius, respectively, than the FC. None of the MMC agents affected hCF morphology and all induced similar hCF viability, proliferation and metabolic activity. Electrophoresis and immunofluorescence analyses made apparent that at day 10 (longest time point assessed), the FC brought about the highest fibronectin and collagen types I, III, IV, V and VI deposition. Deposited ECM pattern analysis showed that at day 10, the FC induced the lowest lacunarity and normalised end points and the highest fractal dimension and % high density matrix. Further immunofluorescence analysis revealed no significant differences between the groups in vimentin, aldehyde dehydrogenase 3 family member A1, keratocan, paired box protein 6 and α-smooth muscle actin. Importantly, at day 10, the FC resulted in the highest growth factor retention (20 molecules). Our data clearly illustrate a MMC agent dependent cell response, with the FC having the highest positive effect in hCF cultures.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110162"},"PeriodicalIF":3.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686462","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":"A modified calculation formula for meibomian gland grading","authors":"Yang Liu ,&nbsp;Yaoyao Ren ,&nbsp;Wenjing Li ,&nbsp;Wei Liu ,&nbsp;Min Ke","doi":"10.1016/j.exer.2024.110166","DOIUrl":"10.1016/j.exer.2024.110166","url":null,"abstract":"<div><div>This study aimed to establish a modified calculation formula for the grading of meibomian glands. Meibography images from 102 participants by different examiners on separate machines on two consecutive days were analyzed, quantified and compared side-by-side. Measure and calculate the ratio of the MGs area to the whole eyelid area and the ratio of the MGs to the corneal base area. Our findings demonstrate that there were significant differences in the ratio of the meibomian gland area to the whole eyelid area between two measurements, but not in the ratio of the meibomian gland area to the corneal base area. The measurement of the eyelid area showed bigger variations and poorer repeatability than the meibomian gland area and the corneal base area. As such, the ratio of the meibomian gland area to the corneal base area is a more stable indicator for the grading of meibomian glands over multiple measurement.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110166"},"PeriodicalIF":3.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686457","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":"Human embryonic stem cell-derived immunity-and-matrix-regulatory cells on collagen scaffold effectively treat rat corneal alkali burn.","authors":"Haimiao Lin, Baojie Guo, Zhongwen Li, Chenxin Wang, Wenyu Wu, Zhaoxiang Lu, Liu Wang, Jun Wu, Jinming Li, Jie Hao, Yun Feng","doi":"10.1016/j.exer.2024.110164","DOIUrl":"10.1016/j.exer.2024.110164","url":null,"abstract":"<p><p>Corneal alkali burns (CAB) are a severe form of ocular injury that often leads to significant vision loss, with limited effective treatment options available beyond corneal transplantation. Immunity and matrix-regulatory cells (IMRCs) have emerged as a promising alternative due to their ability to modulate immune responses and support tissue repair. This study investigates the efficacy of IMRCs on collagen scaffolds (IMRCs-col) for treating CAB in a rat model. We developed a novel treatment combining IMRCs with a collagen scaffold to align with the ocular surface structure. In vitro analyses showed that IMRCs-col significantly upregulated the expression of immune regulatory molecules, including IL-1RA and SCF. Additionally, IMRCs-col effectively inhibited the production of pro-inflammatory cytokines (IL-8 and Gro-a/CXCL1) while promoting pro-regenerative cytokines (bFGF, HGF, and PDGF). In an animal model of CAB, IMRCs-col transplantation demonstrated substantial efficacy in restoring corneal opacity and reducing neovascularization. Histological examination revealed reduced inflammation and improved corneal tissue regeneration compared to untreated CAB. Enhanced activation of pathways associated with anti-inflammatory responses and tissue repair was observed at days 3, 7, and 21 post-treatment.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110164"},"PeriodicalIF":3.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686389","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":"Topical application of 666-15, a potent inhibitor of CREB, alleviates alkali-induced corneal neovascularization","authors":"Zuohong Li ,&nbsp;Jianping Chen ,&nbsp;Zhaohao Huang ,&nbsp;Weifeng Huang ,&nbsp;Kerui Wang ,&nbsp;Xuanwei Liang ,&nbsp;Wenru Su","doi":"10.1016/j.exer.2024.110165","DOIUrl":"10.1016/j.exer.2024.110165","url":null,"abstract":"<div><div>Corneal neovascularization (CNV) is a dynamically regulated process that arises due to a disruption in the equilibrium between pro-angiogenic and anti-angiogenic factors. Various cytokines are released by vascular endothelial cells and macrophages in damaged cornea, ultimately inducing CNV. The cAMP-response element-binding protein (CREB), a nuclear transcription factor, potentially impacts tumor angiogenesis by modulating the secretion of angiogenic proteins. This study aimed to assess the impact of 666-15, a potent inhibitor of CREB, on angiogenesis using human microvascular retinal endothelial cells (HMRECs), RAW 264.7 macrophage cell line and alkali-induce CNV mouse model. In vivo, the topical application of 666-15 (0.05 mg/mL) to the alkali-burn corneas led to 45% reduction in CNV. Additionally, in vitro treatment with 666-15 is effective in suppressing the migration, proliferation, and tube formation by HMRECs. Furthermore, treatment with 666-15 resulted in a down-regulation of pro-angiogenic cytokines expression, including VEGF-A, TGF-β1, b-FGF, and MMP-2 but simultaneously increasing anti-angiogenic cytokines expression, such as ADAMTS-1, Thrombospondin-1 (Tsp-1) and Tsp-2, both in alkali-burn corneas and HMRECs. And 666-15 inhibited the recruitment and the cytokines expression (VEGF-A, MMP-2, IL-1β, TNF-α, MCP-1 and MIP-1) of macrophage. Our findings revealed that 666–15 may suppress the function of endothelial cells and angiogenesis by restoring the homeostasis of pro-angiogenic stimuli, suggesting its potential as a therapeutic agent in the treatment of CNV and other angiogenesis-driven diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110165"},"PeriodicalIF":3.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686395","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":"Role of semaphorin7A in epithelial-mesenchymal transition and proliferative vitreoretinopathy","authors":"Shuang Song ,&nbsp;Rufei Yang ,&nbsp;Ying Su ,&nbsp;Feng Wang","doi":"10.1016/j.exer.2024.110153","DOIUrl":"10.1016/j.exer.2024.110153","url":null,"abstract":"<div><div>Proliferative vitreoretinopathy (PVR) is a multifactorial ocular condition characterized by the development of fibrotic membranes inside the vitreous cavity and on the detached retina, which can result in severe blindness. Semaphorin7A (Sema7a) is involved in axon growth, inflammatory responses, and immune regulation; however, its role in PVR and regulatory mechanisms in retinal pigment epithelium (RPE) cells remains unclear. This study aimed to examine Sema7a in PVR and the underlying mechanisms. Transcriptome sequencing was used to investigate the changes in mRNA expression profiles. Western blotting, immunofluorescence, and real-time polymerase chain reaction (RT-PCR) were utilized to investigate the potential mechanism of Sema7a on epithelial-mesenchymal transition (EMT) in RPE cells. Stimulating RPE cells with transforming growth factor beta-1 (TGF-β1) decreased the levels of epithelial markers but increased those of mesenchymal markers. Based on transcriptome sequencing, many molecules associated with PVR progression were regulated. PVR vitreous fluid proteomics data analysis showed that Sema7a significantly changed at different levels. Silencing <em>Sema7a</em> in RPE cells attenuated TGF-β1-induced EMT and their ability to induce experimental PVR; in contrast, recombinant Sema7a (rSema7a) directly triggered EMT in RPE cells. TGF-β1 induction mechanically activated the PI3k-AKT and MAPK pathways, while Sema7a knockdown by short interfering RNA lowered the phosphorylation of the PI3k-AKT/MAPK signaling pathway. Therefore, Sema7a may be a viable therapeutic target for PVR due to its crucial role in the TGF-β1-induced EMT of RPE cells.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110153"},"PeriodicalIF":3.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681335","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":"Assessment of protein profile in vitreous samples of patients with epiretinal membrane by proteomic approaches","authors":"Fatma Sumer ,&nbsp;Berna Ozkan ,&nbsp;V. Levent Karabas ,&nbsp;Gurler Akpinar ,&nbsp;Murat Kasap","doi":"10.1016/j.exer.2024.110160","DOIUrl":"10.1016/j.exer.2024.110160","url":null,"abstract":"<div><div>This study aims to characterize idiopathic epiretinal membrane (iERM) using proteomic analysis to enhance diagnosis and treatment strategies. In a prospective case-control clinical trial, vitreous fluids (VF) from twelve iERM patients were collected during surgery and analyzed by 2DE-based MALDI TOF-TOF MS/MS. PANTHER and STRING analyses were performed to investigate the biological relationships between the identified proteins and to determine relevant cellular pathways. A total of 148 proteins were identified, including 24 that were unique to iERM. Grouping the proteins by biological processes revealed that most were involved in cell adhesion (n = 6), proteolysis (n = 10), and complement activation (n = 8). Compared to control VF, 12 proteins were upregulated and 12 downregulated in iERM VF, with the differentially expressed proteins strongly associated with inflammation. Proteomic analysis highlighted complement and inflammatory proteins as potential biomarkers or therapeutic targets for iERM. Given that inflammation and fibrosis play critical roles in iERM, further investigation into these differential proteins holds significant clinical relevance. Despite the challenge of recruiting suitable patients, we believe the results of this study provide a valuable foundation for future research.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110160"},"PeriodicalIF":3.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647203","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":"Complement C3 knockout protects photoreceptors in the sodium iodate model","authors":"Tan Wang ,&nbsp;Ying Song ,&nbsp;Brent A. Bell ,&nbsp;Brandon D. Anderson ,&nbsp;Timothy T. Lee ,&nbsp;Weihong Yu ,&nbsp;Joshua L. Dunaief","doi":"10.1016/j.exer.2024.110161","DOIUrl":"10.1016/j.exer.2024.110161","url":null,"abstract":"<div><div>Complement factor 3 (C3) has emerged as a primary therapeutic target in age-related macular degeneration (AMD) supported by genetic, histologic, and clinical trial evidence. Yet, the site(s) of action are unclear. The purpose of this study was to test the effect of C3 knockout on photoreceptors and retinal pigment epithelial cells (RPE) in the sodium iodate (NaIO₃) model, which mirrors some features of AMD. <em>C3</em>^{<em>−/−</em>} and WT mice, both on a C57Bl/6J background, were injected intraperitoneally with 25 mg/kg NaIO₃. Electroretinography and optical coherence tomography were performed 7 days later to assess retinal function and structure, respectively. Then, mice were euthanized for retinal immunohistochemistry, quantitative real-time PCR and enzyme-linked immunosorbent assays. NaIO₃ increased C3 protein levels in the neural retina but not RPE. WT but not <em>C3</em>^{<em>−/−</em>} mice showed NaIO₃-induced iC3b deposition on photoreceptor outer segments. <em>C3</em>^{<em>−/−</em>} mice were partially protected against photoreceptor layer thinning. There was partial preservation of rod and cone function in the <em>C3</em>^{<em>−/−</em>} group. Neither RPE structure nor function was protected. These results suggest outer segment opsonization contributes to photoreceptor death in this model, and that targeting C3 can protect photoreceptor structure and function when RPE cells are stressed.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110161"},"PeriodicalIF":3.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667563","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":"Deferiprone protects photoreceptors by inhibiting ferroptosis after experimental retinal detachment","authors":"Ziyang Ye ,&nbsp;Yuanye Yan ,&nbsp;Feiyu Jin,&nbsp;Jiazhen Jiang,&nbsp;Can Deng,&nbsp;Lisong Wang,&nbsp;Kai Dong","doi":"10.1016/j.exer.2024.110156","DOIUrl":"10.1016/j.exer.2024.110156","url":null,"abstract":"<div><div>The detachment of the retinal neuroepithelium from the retinal pigment epithelium (RPE), often due to a retinal tear and subsequent subretinal fluid (SRF) accumulation, is a critical factor leading to photoreceptor cells (PR) death and permanent vision impairment in retinal detachment (RD) scenarios. Predicting postoperative visual recovery is challenging, even with surgical reattachment. Research has indicated that increased iron and transferrin (TF) saturation in the vitreous fluid (VF) correlates with poorer visual outcomes, suggesting a potential role for ferroptosis, a form of regulated cell death, in PR following RD. To explore this hypothesis, we analyzed the VF of RD patients for ferroptosis markers, revealing reduced levels of glutathione peroxidase 4 (GPX4), glutathione (GSH), and reduced nicotinamide adenine dinucleotide phosphate (NADPH), alongside elevated levels of Long-chain acyl-CoA synthetase 4(ACSL4), malondialdehyde (MDA), and ferrous iron. We then developed a mouse model to simulate RD and administered the iron chelator deferiprone (DFP) as a treatment. Our findings indicated that DFP mitigated ferroptosis in the retina, thereby preserving retinal architecture and function. Collectively, our study establishes the occurrence of ferroptosis in RD and demonstrates the therapeutic potential of DFP in protecting PR and treating RD.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110156"},"PeriodicalIF":3.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644303","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":"SN promote retinal pathological neovascularization through activation of EGFR, IR and IGF-1R","authors":"Wen Deng ,&nbsp;Kongqian Huang ,&nbsp;Ling Cui ,&nbsp;Zhijie Niu ,&nbsp;Diyang Ke ,&nbsp;Li Jiang ,&nbsp;Ningning Tang ,&nbsp;Haibin Zhong ,&nbsp;Qianqian Lan ,&nbsp;Fan Xu ,&nbsp;Fen Tang","doi":"10.1016/j.exer.2024.110158","DOIUrl":"10.1016/j.exer.2024.110158","url":null,"abstract":"<div><div>Secretoneurin (SN) is a neuropeptide derived from secretogranin II (SgII), mainly are involved in neuroendocrine system. The present study is aimed to investigate the role of SN in retinal pathological neovascularization and physiological vasculature. In the study, we found the overexpression of SgII in retina of Oxygen-Induced Retinopathy (OIR) mouse model, and <em>SgII</em> knockdown could alleviate pathological retinal neovascularization in OIR. Conversely, <em>SgII</em> knockdown have no detectable effect in embryonic physiological vasculature. Experiments <em>in vitro</em> and <em>in vivo</em> further verified SN's angiogenic effect on the eye. In further, we identified that SN promoted angiogenesis via activation of Epidermal Growth Factor Receptor (EGFR), Insulin Receptor (IR), and Insulin-like Growth Factor 1 Receptor (IGF-1R), and followed by the phosphorylation of PI3K-AKT-mTOR signaling. In summarize, our study suggests that SN might be a postnatal angiogenic factor, which was critically involved in retinal pathological neovascularization, but not in embryonic retinal physiological vasculature. Moreover, we identified the receptors and the downstream signaling involved in SN induced retinal angiogenesis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110158"},"PeriodicalIF":3.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644304","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}