{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:43:46Z","timestamp":1787021026389,"version":"build-2736575974"},"reference-count":125,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2024J011453"],"award-info":[{"award-number":["2024J011453"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","award":["2023CXA055"],"award-info":[{"award-number":["2023CXA055"]}],"id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To summarize the role of endoplasmic reticulum stress (ERS) in the pathogenesis of diabetic retinopathy (DR) and evaluate potential ERS-targeted interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review analyzes recent preclinical and clinical studies focusing on the molecular mechanisms of ERS and its impact on retinal inflammation, oxidative stress, and angiogenesis in DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ERS, triggered by hyperglycemia-induced oxidative stress and glucotoxicity, activates the unfolded protein response (UPR) via inositol-requiring enzyme 1 (IRE1), PKR-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) pathways. While initially protective, prolonged ERS leads to apoptosis, chronic inflammation, and neovascularization. Key downstream mediators include C\/EBP homologous protein (CHOP), X-box binding protein 1 (XBP1), and activating transcription factor 4 (ATF4). ERS inhibitors such as 4-phenylbutyric acid and tauroursodeoxycholic acid, along with selective modulators of UPR signaling, have shown neuroprotective and anti-inflammatory effects in DR models. Combination therapies integrating antioxidants and anti-inflammatory agents demonstrate synergistic efficacy. However, clinical translation remains limited by delivery barriers and incomplete understanding of UPR-specific actions in the human retina.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Targeting ERS presents a promising therapeutic strategy for DR, with the potential to preserve vision and improve outcomes for diabetic patients. Future research should focus on elucidating the precise molecular pathways and developing targeted, personalized ERS-modulating therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40659-026-00675-0","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:52:44Z","timestamp":1769590364000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting endoplasmic reticulum stress in diabetic retinopathy: mechanistic insights and emerging therapies"],"prefix":"10.1186","volume":"59","author":[{"given":"Junting","family":"Weng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danjuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanjiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8938-6153","authenticated-orcid":false,"given":"Shuoyun","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"675_CR1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.survophthal.2024.02.004","volume":"69","author":"F Jiang","year":"2024","unstructured":"Jiang F, Lei C, Chen Y, et al. The complement system and diabetic retinopathy. Surv Ophthalmol. 2024;69:575\u201384. https:\/\/doi.org\/10.1016\/j.survophthal.2024.02.004.","journal-title":"Surv Ophthalmol"},{"key":"675_CR2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/1061186X.2024.2316775","volume":"32","author":"R Wang","year":"2024","unstructured":"Wang R, Rao S, Zhong Z, et al. Emerging role of ferroptosis in diabetic retinopathy: a review. J Drug Target. 2024;32:393\u2013403. 2024\/02\/22.","journal-title":"J Drug Target"},{"key":"675_CR3","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/aos.14644","volume":"99","author":"Y Xu","year":"2021","unstructured":"Xu Y, Wang A, Lin X, et al. Global burden and gender disparity of vision loss associated with diabetes retinopathy. Acta Ophthalmol. 2021;99:431\u201340. 2020\/10\/31.","journal-title":"Acta Ophthalmol"},{"key":"675_CR4","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1080\/09273948.2022.2027464","volume":"31","author":"EA Rani","year":"2023","unstructured":"Rani EA, Janani R, Chonche MJ, et al. Lactucaxanthin regulates the cascade of retinal oxidative stress, endoplasmic reticulum stress and inflammatory signaling in diabetic rats. Ocul Immunol Inflamm. 2023;31:320\u20138. 2022\/01\/27.","journal-title":"Ocul Immunol Inflamm"},{"key":"675_CR5","doi-asserted-by":"publisher","first-page":"820","DOI":"10.3389\/fphys.2018.00820","volume":"9","author":"AR Santiago","year":"2018","unstructured":"Santiago AR, Boia R, Aires ID, et al. Sweet stress: coping with vascular dysfunction in diabetic retinopathy. Front Physiol. 2018;9:820. https:\/\/doi.org\/10.3389\/fphys.2018.00820.","journal-title":"Front Physiol"},{"key":"675_CR6","doi-asserted-by":"publisher","first-page":"101231","DOI":"10.1016\/j.preteyeres.2023.101231","volume":"98","author":"SX Zhang","year":"2024","unstructured":"Zhang SX, Wang JJ, Starr CR, et al. The Endoplasmic reticulum: homeostasis and crosstalk in retinal health and disease. Prog Retin Eye Res. 2024;98:101231. https:\/\/doi.org\/10.1016\/j.preteyeres.2023.101231.","journal-title":"Prog Retin Eye Res"},{"key":"675_CR7","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2021.5240","author":"P Shi","year":"2021","unstructured":"Shi P, Zhang Z, Xu J, et al. Endoplasmic reticulum stress\u2013induced cell death as a potential mechanism for targeted therapy in glioblastoma (Review). Int J Oncol. 2021. https:\/\/doi.org\/10.3892\/ijo.2021.5240","journal-title":"Int J Oncol"},{"key":"675_CR8","doi-asserted-by":"crossref","first-page":"109699","DOI":"10.1016\/j.biopha.2019.109699","volume":"124","author":"Y Wang","year":"2020","unstructured":"Wang Y, Wang L, Guo H, et al. Knockdown of MALAT1 attenuates high-glucose-induced angiogenesis and inflammation via Endoplasmic reticulum stress in human retinal vascular endothelial cells. Biomed Pharmacother = Biomed Pharmacother. 2020;124:109699. 2020\/01\/28.","journal-title":"Biomed Pharmacother = Biomed Pharmacother"},{"key":"675_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10050967","author":"P Wadgaonkar","year":"2022","unstructured":"Wadgaonkar P, Bi Z, Wan J, et al. Arsenic activates the ER stress-associated unfolded protein response via the activating transcription factor 6 in human bronchial epithelial cells. Biomedicines. 2022. https:\/\/doi.org\/10.3390\/biomedicines10050967","journal-title":"Biomedicines"},{"key":"675_CR10","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/160140","author":"JH Ma","year":"2014","unstructured":"Ma JH, Wang JJ, Zhang SX. The unfolded protein response and diabetic retinopathy. J Diabetes Res. 2014. https:\/\/doi.org\/10.1155\/2014\/160140","journal-title":"J Diabetes Res"},{"key":"675_CR11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2147\/vhrm.2008.04.01.115","volume":"4","author":"T Oshitari","year":"2008","unstructured":"Oshitari T, Hata N, Yamamoto S. Endoplasmic reticulum stress and diabetic retinopathy. Vasc Health Risk Manag. 2008;4:115\u201322. https:\/\/doi.org\/10.2147\/vhrm.2008.04.01.115.","journal-title":"Vasc Health Risk Manag"},{"key":"675_CR12","doi-asserted-by":"publisher","first-page":"696","DOI":"10.2337\/db12-1469","volume":"62","author":"NE Cameron","year":"2013","unstructured":"Cameron NE. Role of endoplasmic reticulum stress in diabetic neuropathy. Diabetes. 2013;62:696\u20137. https:\/\/doi.org\/10.2337\/db12-1469.","journal-title":"Diabetes"},{"key":"675_CR13","doi-asserted-by":"crossref","first-page":"615125","DOI":"10.3389\/fncel.2020.615125","volume":"14","author":"K Alam","year":"2020","unstructured":"Alam K, Akhter Y. The impacts of unfolded protein response in the retinal cells during diabetes: possible implications on diabetic retinopathy development. Front Cell Neurosci. 2020;14:615125. 2021\/02\/23.","journal-title":"Front Cell Neurosci"},{"key":"675_CR14","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1111\/aos.14573","volume":"99","author":"Y Shan","year":"2021","unstructured":"Shan Y, Xu Y, Lin X, et al. Burden of vision loss due to diabetic retinopathy in China from 1990 to 2017: findings from the global burden of disease study. Acta Ophthalmol. 2021;99:e267\u201373. 2020\/09\/02.","journal-title":"Acta Ophthalmol"},{"key":"675_CR15","doi-asserted-by":"publisher","first-page":"Cd006127","DOI":"10.1002\/14651858.CD006127.pub3","volume":"3","author":"DV Do","year":"2023","unstructured":"Do DV, Han G, Abariga SA, et al. Blood pressure control for diabetic retinopathy. Cochrane Database Syst Rev. 2023;3:Cd006127. https:\/\/doi.org\/10.1002\/14651858.CD006127.pub3","journal-title":"Cochrane Database Syst Rev"},{"key":"675_CR16","doi-asserted-by":"publisher","first-page":"e0285302","DOI":"10.1371\/journal.pone.0285302","volume":"18","author":"AX Chan","year":"2023","unstructured":"Chan AX, McDermott Iv JJ, Lee TC, et al. Correction: Associations between healthcare utilization and access and diabetic retinopathy complications using all of Us nationwide survey data. PLoS ONE. 2023;18:e0285302. https:\/\/doi.org\/10.1371\/journal.pone.0285302.","journal-title":"PLoS ONE"},{"key":"675_CR17","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1177\/10815589221145040","volume":"71","author":"M Estaji","year":"2023","unstructured":"Estaji M, Hosseini B, Bozorg-Qomi S, et al. Pathophysiology and diagnosis of diabetic retinopathy: a narrative review. J Invest Med: Off Publ Am Fed Clin Res. 2023;71:265\u201378. https:\/\/doi.org\/10.1177\/10815589221145040.","journal-title":"J Invest Med: Off Publ Am Fed Clin Res"},{"key":"675_CR18","doi-asserted-by":"publisher","DOI":"10.2174\/0115733998296228240521151050","author":"DS Pushparani","year":"2024","unstructured":"Pushparani DS, Varalakshmi J, Roobini K, et al. Diabetic retinopathy-a review. Curr Diabetes Rev. 2024. https:\/\/doi.org\/10.2174\/0115733998296228240521151050","journal-title":"Curr Diabetes Rev"},{"key":"675_CR19","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.ajo.2009.07.007","volume":"148","author":"X Wang","year":"2009","unstructured":"Wang X, Wang G, Wang Y. Intravitreous vascular endothelial growth factor and hypoxia-inducible factor 1a in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2009;148:883\u20139. 2009\/10\/20.","journal-title":"Am J Ophthalmol"},{"key":"675_CR20","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/09273948.2020.1811350","volume":"30","author":"KS Raman","year":"2022","unstructured":"Raman KS, Matsubara JA. Dysregulation of the NLRP3 inflammasome in diabetic retinopathy and potential therapeutic targets. Ocul Immunol Inflamm. 2022;30:470\u20138. 2020\/10\/08.","journal-title":"Ocul Immunol Inflamm"},{"key":"675_CR21","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10010050","author":"L\u00c1 Ortega","year":"2021","unstructured":"Ortega L\u00c1. Oxidative stress in diabetic retinopathy. Antioxid (Basel Switzerland). 2021. https:\/\/doi.org\/10.3390\/antiox10010050","journal-title":"Antioxid (Basel Switzerland)"},{"key":"675_CR22","doi-asserted-by":"publisher","first-page":"3223","DOI":"10.1007\/s10792-021-01864-4","volume":"41","author":"D Soni","year":"2021","unstructured":"Soni D, Sagar P, Takkar B. Diabetic retinal neurodegeneration as a form of diabetic retinopathy. Int Ophthalmol. 2021;41:3223\u201348. https:\/\/doi.org\/10.1007\/s10792-021-01864-4.","journal-title":"Int Ophthalmol"},{"key":"675_CR23","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13148-023-01619-1","volume":"16","author":"C Cai","year":"2024","unstructured":"Cai C, Gu C, He S, et al. TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy. Clin Epigenetics. 2024;16:6. https:\/\/doi.org\/10.1186\/s13148-023-01619-1.","journal-title":"Clin Epigenetics"},{"key":"675_CR24","doi-asserted-by":"publisher","first-page":"e701","DOI":"10.1002\/mco2.701","volume":"5","author":"Y Liu","year":"2024","unstructured":"Liu Y, Xu C, Gu R, et al. Endoplasmic reticulum stress in diseases. MedComm. 2024;5:e701. https:\/\/doi.org\/10.1002\/mco2.701.","journal-title":"MedComm"},{"key":"675_CR25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41569-021-00511-w","volume":"18","author":"J Ren","year":"2021","unstructured":"Ren J, Bi Y, Sowers JR, et al. Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases. Nat Reviews Cardiol. 2021;18:499\u2013521. https:\/\/doi.org\/10.1038\/s41569-021-00511-w.","journal-title":"Nat Reviews Cardiol"},{"key":"675_CR26","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.canlet.2020.07.009","volume":"490","author":"N McCarthy","year":"2020","unstructured":"McCarthy N, Dolgikh N, Logue S, et al. The IRE1 and PERK arms of the unfolded protein response promote survival of rhabdomyosarcoma cells. Cancer Lett. 2020;490:76\u201388. https:\/\/doi.org\/10.1016\/j.canlet.2020.07.009.","journal-title":"Cancer Lett"},{"key":"675_CR27","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-024-05014-z","author":"L Zhou","year":"2024","unstructured":"Zhou L, Zhu X, Lei S, et al. The role of the ER stress sensor IRE1 in cardiovascular diseases. Mol Cell Biochem. 2024. https:\/\/doi.org\/10.1007\/s11010-024-05014-z","journal-title":"Mol Cell Biochem"},{"key":"675_CR28","doi-asserted-by":"publisher","first-page":"118740","DOI":"10.1016\/j.lfs.2020.118740","volume":"265","author":"S Bashir","year":"2021","unstructured":"Bashir S, Banday M, Qadri O, et al. The molecular mechanism and functional diversity of UPR signaling sensor IRE1. Life Sci. 2021;265:118740. https:\/\/doi.org\/10.1016\/j.lfs.2020.118740","journal-title":"Life Sci"},{"key":"675_CR29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fmolb.2019.00011","volume":"6","author":"CJ Adams","year":"2019","unstructured":"Adams CJ, Kopp MC, Larburu N, et al. Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front Mol Biosci. 2019;6:11. 2019\/04\/02.","journal-title":"Front Mol Biosci"},{"key":"675_CR30","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s44318-023-00014-z","volume":"43","author":"L Neidhardt","year":"2024","unstructured":"Neidhardt L, Cloots E, Friemel N, et al. The IRE1\u03b2-mediated unfolded protein response is repressed by the chaperone AGR2 in mucin producing cells. EMBO J. 2024;43:719\u201353. 2024\/01\/05.","journal-title":"EMBO J"},{"key":"675_CR31","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/jnc.14216","volume":"143","author":"DR Masser","year":"2017","unstructured":"Masser DR, Otalora L, Clark NW, et al. Functional changes in the neural retina occur in the absence of mitochondrial dysfunction in a rodent model of diabetic retinopathy. J Neurochem. 2017;143:595\u2013608. 2017\/09\/14.","journal-title":"J Neurochem"},{"key":"675_CR32","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41419-024-06701-x","volume":"15","author":"M Blanc","year":"2024","unstructured":"Blanc M, Habbouche L, Xiao P, et al. Bax inhibitor-1 preserves pancreatic \u03b2-cell proteostasis by limiting proinsulin misfolding and programmed cell death. Cell Death Dis. 2024;15:334. 2024\/05\/15.","journal-title":"Cell Death Dis"},{"key":"675_CR33","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbrc.2020.06.036","volume":"529","author":"Y Xiong","year":"2020","unstructured":"Xiong Y, Wang Y, Xiong Y, et al. Salidroside alleviated hypoxia-induced liver injury by inhibiting endoplasmic reticulum stress-mediated apoptosis via IRE1\u03b1\/JNK pathway. Biochem Biophys Res Commun. 2020;529:335\u201340. 2020\/07\/25.","journal-title":"Biochem Biophys Res Commun"},{"key":"675_CR34","doi-asserted-by":"crossref","first-page":"383","DOI":"10.18240\/ijo.2025.03.02","volume":"18","author":"LZ Wang","year":"2025","unstructured":"Wang LZ, Yan JJ. GPR120\/FFAR4 protects retinal vascular endothelial cells against high glucose injury via suppressing ROS-ERS mediated apoptosis. Int J Ophthalmol. 2025;18:383\u20139. 2025\/03\/19.","journal-title":"Int J Ophthalmol"},{"key":"675_CR35","doi-asserted-by":"crossref","first-page":"1405546","DOI":"10.3389\/fcell.2024.1405546","volume":"12","author":"K Zhao","year":"2024","unstructured":"Zhao K, Zhang H, Yang D. SIRT1 exerts protective effects by inhibiting endoplasmic reticulum stress and NF-\u03baB signaling pathways. Front Cell Dev Biology. 2024;12:1405546. 2024\/05\/15.","journal-title":"Front Cell Dev Biology"},{"key":"675_CR36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1167\/iovs.65.4.23","volume":"65","author":"A Leonardi","year":"2024","unstructured":"Leonardi A, Donato A, Rosani U, et al. Endoplasmic reticulum stress and unfolded protein response in vernal keratoconjunctivitis. Investig Ophthalmol Vis Sci. 2024;65:23. 2024\/04\/10.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"675_CR37","doi-asserted-by":"crossref","first-page":"6108","DOI":"10.1002\/fsn3.4289","volume":"12","author":"F Mirzavi","year":"2024","unstructured":"Mirzavi F, Rajabian A, Hosseini H. The potential protective role of carotenoids from saffron: a focus on endoplasmic reticulum stress-related organ damage. Food Sci Nutr. 2024;12:6108\u201322. 2024\/11\/18.","journal-title":"Food Sci Nutr"},{"key":"675_CR38","doi-asserted-by":"crossref","first-page":"115981","DOI":"10.1016\/j.envpol.2020.115981","volume":"272","author":"X Wang","year":"2021","unstructured":"Wang X, Zhuang Y, Fang Y, et al. Endoplasmic reticulum stress aggravates copper-induced apoptosis via the PERK\/ATF4\/CHOP signaling pathway in Duck renal tubular epithelial cells. Environ Pollut (Barking Essex: 1987). 2021;272:115981. 2020\/11\/30.","journal-title":"Environ Pollut (Barking Essex: 1987)"},{"key":"675_CR39","doi-asserted-by":"publisher","first-page":"37375","DOI":"10.1074\/jbc.M303619200","volume":"278","author":"S Luo","year":"2003","unstructured":"Luo S, Baumeister P, Yang S, et al. Induction of Grp78\/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF\/CRE site independent of the Endoplasmic reticulum stress elements. J Biol Chem. 2003;278:37375\u201385. https:\/\/doi.org\/10.1074\/jbc.M303619200.","journal-title":"J Biol Chem"},{"key":"675_CR40","doi-asserted-by":"crossref","first-page":"115711","DOI":"10.1016\/j.ecoenv.2023.115711","volume":"268","author":"H Zhang","year":"2023","unstructured":"Zhang H, Ran M, Jiang L, et al. Mitochondrial dysfunction and endoplasmic reticulum stress induced by activation of PPAR\u03b1 leaded testicular to apoptosis in SD rats explored to di-(2-ethylhexyl) phthalate (DEHP). Ecotoxicol Environ Saf. 2023;268:115711. 2023\/11\/19.","journal-title":"Ecotoxicol Environ Saf"},{"key":"675_CR41","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.molmed.2019.03.005","volume":"25","author":"CC Glembotski","year":"2019","unstructured":"Glembotski CC, Rosarda JD, Wiseman RL. Proteostasis and beyond: ATF6 in ischemic disease. Trends Mol Med. 2019;25:538\u201350. https:\/\/doi.org\/10.1016\/j.molmed.2019.03.005.","journal-title":"Trends Mol Med"},{"key":"675_CR42","doi-asserted-by":"crossref","first-page":"43046","DOI":"10.1074\/jbc.M408466200","volume":"279","author":"J Shen","year":"2004","unstructured":"Shen J, Prywes R. Dependence of site-2 protease cleavage of ATF6 on prior site-1 protease digestion is determined by the size of the luminal domain of ATF6. J Biol Chem. 2004;279:43046\u201351. 2004\/08\/10.","journal-title":"J Biol Chem"},{"key":"675_CR43","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1002\/jcb.26296","volume":"119","author":"S Ghaderi","year":"2018","unstructured":"Ghaderi S, Ahmadian S, Soheili ZS, et al. AAV delivery of GRP78\/BiP promotes adaptation of human RPE cell to ER stress. J Cell Biochem. 2018;119:1355\u201367. 2017\/08\/08.","journal-title":"J Cell Biochem"},{"key":"675_CR44","doi-asserted-by":"crossref","first-page":"14164","DOI":"10.1074\/jbc.RA120.014173","volume":"295","author":"RB Sharma","year":"2020","unstructured":"Sharma RB, Darko C, Alonso LC. Intersection of the ATF6 and XBP1 ER stress pathways in mouse islet cells. J Biol Chem. 2020;295:14164\u201377. 2020\/08\/14.","journal-title":"J Biol Chem"},{"key":"675_CR45","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/jcmm.16255","volume":"25","author":"M Moncan","year":"2021","unstructured":"Moncan M, Mnich K, Blomme A, et al. Regulation of lipid metabolism by the unfolded protein response. J Cell Mol Med. 2021;25:1359\u201370. 2021\/01\/06.","journal-title":"J Cell Mol Med"},{"key":"675_CR46","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cellsig.2013.11.008","volume":"26","author":"KH Tay","year":"2014","unstructured":"Tay KH, Luan Q, Croft A, et al. Sustained IRE1 and ATF6 signaling is important for survival of melanoma cells undergoing ER stress. Cell Signal. 2014;26:287\u201394. 2013\/11\/19.","journal-title":"Cell Signal"},{"key":"675_CR47","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.arcmed.2020.02.001","volume":"51","author":"C Sankaranarayanan","year":"2020","unstructured":"Sankaranarayanan C, Kalaivani K. Isopulegol mitigates hyperglycemia mediated oxidative and endoplasmic reticulum stress in HFD\/STZ induced diabetic rats. Arch Med Res. 2020;51:204\u201314. https:\/\/doi.org\/10.1016\/j.arcmed.2020.02.001.","journal-title":"Arch Med Res"},{"key":"675_CR48","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","volume":"8","author":"X Chen","year":"2023","unstructured":"Chen X, Shi C, He M, et al. Endoplasmic reticulum stress: molecular mechanism and therapeutic targets. Signal Transduct Target Therapy. 2023;8:352. https:\/\/doi.org\/10.1038\/s41392-023-01570-w.","journal-title":"Signal Transduct Target Therapy"},{"key":"675_CR49","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1111\/iwj.13950","volume":"20","author":"L Ma","year":"2023","unstructured":"Ma L, Hua L, Yu W, et al. TSG-6 inhibits hypertrophic Scar fibroblast proliferation by regulating IRE1\u03b1\/TRAF2\/NF-\u03baB signalling. Int Wound J. 2023;20:1008\u201319. https:\/\/doi.org\/10.1111\/iwj.13950.","journal-title":"Int Wound J"},{"key":"675_CR50","doi-asserted-by":"crossref","first-page":"e23512","DOI":"10.1096\/fj.202301592R","volume":"38","author":"RR Lim","year":"2024","unstructured":"Lim RR, Mahaling B, Tan A, et al. ITF2357 regulates NF-\u03baB signaling pathway to protect barrier integrity in retinal pigment epithelial cells. FASEB J: Off Publ Fed Am Soc Exp Biol. 2024;38:e23512. 2024\/03\/02.","journal-title":"FASEB J: Off Publ Fed Am Soc Exp Biol"},{"key":"675_CR51","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.jdiacomp.2018.05.006","volume":"32","author":"P Brito","year":"2018","unstructured":"Brito P, Costa J, Gomes N, et al. Serological inflammatory factors as biomarkers for anatomic response in diabetic macular edema treated with anti-VEGF. J Diabetes Complicat. 2018;32:643\u20139. 2018\/05\/31.","journal-title":"J Diabetes Complicat"},{"key":"675_CR52","doi-asserted-by":"publisher","first-page":"104103","DOI":"10.1016\/j.mvr.2020.104103","volume":"133","author":"JH Yun","year":"2021","unstructured":"Yun JH. Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy. Microvasc Res. 2021;133:104103. https:\/\/doi.org\/10.1016\/j.mvr.2020.104103","journal-title":"Microvasc Res"},{"key":"675_CR53","doi-asserted-by":"publisher","first-page":"e95","DOI":"10.1016\/j.jcjo.2019.09.004","volume":"55","author":"AM Elhusseiny","year":"2020","unstructured":"Elhusseiny AM, Smiddy WE. Carboplatin- and\/or paclitaxel-induced ischemic retinopathy. Can J Ophthalmol J Can D\u2019Ophtalmologie. 2020;55:e95\u20138. https:\/\/doi.org\/10.1016\/j.jcjo.2019.09.004","journal-title":"Can J Ophthalmol J Can D\u2019Ophtalmologie"},{"key":"675_CR54","doi-asserted-by":"crossref","first-page":"114595","DOI":"10.1016\/j.jep.2021.114595","volume":"282","author":"Y Li","year":"2022","unstructured":"Li Y, Fu Y, Sun J, et al. Tanshinone IIA alleviates NLRP3 inflammasome-mediated pyroptosis in Mycobacterium tuberculosis-(H37Ra-) infected macrophages by inhibiting endoplasmic reticulum stress. J Ethnopharmacol. 2022;282:114595. 2021\/09\/14.","journal-title":"J Ethnopharmacol"},{"key":"675_CR55","doi-asserted-by":"crossref","first-page":"108335","DOI":"10.1016\/j.exer.2020.108335","volume":"202","author":"X Chu","year":"2021","unstructured":"Chu X, Wang C, Wu Z, et al. JNK\/c-Jun-driven NLRP3 inflammasome activation in microglia contributed to retinal ganglion cells degeneration induced by indirect traumatic optic neuropathy. Exp Eye Res. 2021;202:108335. 2020\/11\/04.","journal-title":"Exp Eye Res"},{"key":"675_CR56","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.7150\/thno.11685","volume":"5","author":"SR Kim","year":"2015","unstructured":"Kim SR, Kim HJ, Kim DI, et al. Blockade of interplay between IL-17A and Endoplasmic reticulum stress attenuates LPS-Induced lung injury. Theranostics. 2015;5:1343\u201362. 2015\/10\/31.","journal-title":"Theranostics"},{"key":"675_CR57","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24020913","author":"G Lupo","year":"2023","unstructured":"Lupo G, Agafonova A, Cosentino A, et al. Protective effects of human pericyte-like adipose-derived mesenchymal stem cells on human retinal endothelial cells in an in vitro model of diabetic retinopathy: evidence for autologous cell therapy. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24020913.","journal-title":"Int J Mol Sci"},{"key":"675_CR58","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12974-022-02477-z","volume":"19","author":"J Huang","year":"2022","unstructured":"Huang J, Li Z, Hu Y, et al. Melatonin, an endogenous hormone, modulates Th17 cells via the reactive-oxygen species\/TXNIP\/HIF-1\u03b1 axis to alleviate autoimmune uveitis. J Neuroinflamm. 2022;19:124. 2022\/05\/28.","journal-title":"J Neuroinflamm"},{"key":"675_CR59","doi-asserted-by":"publisher","first-page":"9028483","DOI":"10.1155\/2019\/9028483","volume":"2019","author":"S Wu","year":"2019","unstructured":"Wu S, Zhu X, Guo B et al. Unfolded protein response pathways correlatively modulate endoplasmic reticulum stress responses in rat retinal M\u00fcller cells. J Ophthalmol. 2019; 2019:9028483. https:\/\/doi.org\/10.1155\/2019\/9028483","journal-title":"J Ophthalmol"},{"key":"675_CR60","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2337\/db11-0315","volume":"61","author":"Y Zhong","year":"2012","unstructured":"Zhong Y, Li J, Chen Y, et al. Activation of Endoplasmic reticulum stress by hyperglycemia is essential for M\u00fcller cell-derived inflammatory cytokine production in diabetes. Diabetes. 2012;61:492\u2013504. 2012\/01\/10.","journal-title":"Diabetes"},{"key":"675_CR61","doi-asserted-by":"crossref","first-page":"114685","DOI":"10.1016\/j.fct.2024.114685","volume":"188","author":"M Aschner","year":"2024","unstructured":"Aschner M, Skalny AV, Paoliello MMB, et al. Retinal toxicity of heavy metals and its involvement in retinal pathology. Food Chem Toxicology: Int J Published Br Industrial Biol Res Association. 2024;188:114685. 2024\/04\/26.","journal-title":"Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc"},{"key":"675_CR62","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/febs.14522","volume":"286","author":"H Kroeger","year":"2019","unstructured":"Kroeger H, Chiang WC, Felden J, et al. ER stress and unfolded protein response in ocular health and disease. FEBS J. 2019;286:399\u2013412. 2018\/05\/29.","journal-title":"FEBS J"},{"key":"675_CR63","doi-asserted-by":"crossref","first-page":"680947","DOI":"10.3389\/fcell.2021.680947","volume":"9","author":"Y Xiao","year":"2021","unstructured":"Xiao Y, Hu X, Fan S, et al. Single-Cell transcriptome profiling reveals the suppressive role of retinal neurons in microglia activation under diabetes mellitus. Front Cell Dev Biology. 2021;9:680947. 2021\/08\/27.","journal-title":"Front Cell Dev Biology"},{"key":"675_CR64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1113\/EP085794","volume":"102","author":"RM Restaino","year":"2017","unstructured":"Restaino RM, Deo SH, Parrish AR, et al. Increased monocyte-derived reactive oxygen species in type 2 diabetes: role of Endoplasmic reticulum stress. Exp Physiol. 2017;102:139\u201353. 2016\/11\/20.","journal-title":"Exp Physiol"},{"key":"675_CR65","doi-asserted-by":"crossref","first-page":"152540","DOI":"10.1016\/j.tox.2020.152540","volume":"442","author":"JH Quan","year":"2020","unstructured":"Quan JH, Gao FF, Lee M, et al. Involvement of endoplasmic reticulum stress response and IRE1-mediated ASK1\/JNK\/Mcl-1 pathways in silver nanoparticle-induced apoptosis of human retinal pigment epithelial cells. Toxicology. 2020;442:152540. 2020\/07\/28.","journal-title":"Toxicology"},{"key":"675_CR66","doi-asserted-by":"crossref","first-page":"7350","DOI":"10.1074\/jbc.RA120.013093","volume":"295","author":"WP Miller","year":"2020","unstructured":"Miller WP, Sunilkumar S, Giordano JF, et al. The stress response protein REDD1 promotes diabetes-induced oxidative stress in the retina by Keap1-independent Nrf2 degradation. J Biol Chem. 2020;295:7350\u201361. 2020\/04\/17.","journal-title":"J Biol Chem"},{"key":"675_CR67","doi-asserted-by":"crossref","first-page":"877175","DOI":"10.3389\/fphar.2022.877175","volume":"13","author":"W Zhang","year":"2022","unstructured":"Zhang W, Ye F, Pang N, et al. Restoration of sarco\/endoplasmic reticulum Ca(2+)-ATPase activity functions as a pivotal therapeutic target of anti-glutamate-induced excitotoxicity to attenuate endoplasmic reticulum Ca(2+) depletion. Front Pharmacol. 2022;13:877175. 2022\/05\/07.","journal-title":"Front Pharmacol"},{"key":"675_CR68","doi-asserted-by":"crossref","first-page":"e3172","DOI":"10.1038\/cddis.2017.566","volume":"8","author":"K Kapupara","year":"2017","unstructured":"Kapupara K, Wen YT, Tsai RK, et al. Soluble P-selectin promotes retinal ganglion cell survival through activation of Nrf2 signaling after ischemia injury. Cell Death Dis. 2017;8:e3172. 2017\/11\/17.","journal-title":"Cell Death Dis"},{"key":"675_CR69","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1080\/15321819.2020.1726774","volume":"41","author":"A Ahmad","year":"2020","unstructured":"Ahmad A, Ahsan H. Biomarkers of inflammation and oxidative stress in ophthalmic disorders. J Immunoassay Immunochem. 2020;41:257\u201371. https:\/\/doi.org\/10.1080\/15321819.2020.1726774.","journal-title":"J Immunoassay Immunochem"},{"key":"675_CR70","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3892\/ijmm.2015.2418","volume":"37","author":"B Lv","year":"2016","unstructured":"Lv B, Chen T, Xu Z, et al. Crocin protects retinal ganglion cells against H2O2-induced damage through the mitochondrial pathway and activation of NF-\u03baB. Int J Mol Med. 2016;37:225\u201332. 2016\/01\/01.","journal-title":"Int J Mol Med"},{"key":"675_CR71","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.chemosphere.2019.04.026","volume":"227","author":"ZL Jia","year":"2019","unstructured":"Jia ZL, Cen J, Wang JB, et al. Mechanism of isoniazid-induced hepatotoxicity in zebrafish larvae: activation of ROS-mediated ERS, apoptosis and the Nrf2 pathway. Chemosphere. 2019;227:541\u201350. 2019\/04\/21.","journal-title":"Chemosphere"},{"key":"675_CR72","doi-asserted-by":"publisher","first-page":"101799","DOI":"10.1016\/j.redox.2020.101799","volume":"37","author":"Q Kang","year":"2020","unstructured":"Kang Q, Yang C. Oxidative stress and diabetic retinopathy: molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol. 2020;37:101799. https:\/\/doi.org\/10.1016\/j.redox.2020.101799","journal-title":"Redox Biol"},{"key":"675_CR73","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41419-020-03103-7","volume":"11","author":"R Zhang","year":"2020","unstructured":"Zhang R, Shen W, Du J, et al. Selective knockdown of hexokinase 2 in rods leads to age-related photoreceptor degeneration and retinal metabolic remodeling. Cell Death Dis. 2020;11:885. 2020\/10\/22.","journal-title":"Cell Death Dis"},{"key":"675_CR74","doi-asserted-by":"publisher","first-page":"e1007627","DOI":"10.1371\/journal.pgen.1007627","volume":"14","author":"DM Van Den Brink","year":"2018","unstructured":"Van Den Brink DM, Cubizolle A, Chatelain G, et al. Physiological and pathological roles of FATP-mediated lipid droplets in drosophila and mice retina. PLoS Genet. 2018;14:e1007627. https:\/\/doi.org\/10.1371\/journal.pgen.1007627.","journal-title":"PLoS Genet"},{"key":"675_CR75","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030569","author":"C Sarcinelli","year":"2020","unstructured":"Sarcinelli C, Dragic H, Piecyk M, et al. ATF4-dependent NRF2 transcriptional regulation promotes antioxidant protection during endoplasmic reticulum stress. Cancers. 2020. https:\/\/doi.org\/10.3390\/cancers12030569","journal-title":"Cancers"},{"key":"675_CR76","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12071465","author":"F Buonfiglio","year":"2023","unstructured":"Buonfiglio F, B\u00f6hm EW, Pfeiffer N et al. Oxidative stress: a suitable therapeutic target for optic nerve diseases? Antioxidants (Basel, Switzerland) 2023. https:\/\/doi.org\/10.3390\/antiox12071465","journal-title":"Antioxidants (Basel, Switzerland)"},{"key":"675_CR77","doi-asserted-by":"publisher","first-page":"8908960","DOI":"10.1155\/2019\/8908960","volume":"2019","author":"P Wang","year":"2019","unstructured":"Wang P, Chen F, Wang W, et al. Hydrogen sulfide attenuates high glucose-induced human retinal pigment epithelial cell inflammation by inhibiting ROS formation and NLRP3 inflammasome activation. Mediat Inflamm. 2019;2019:8908960. https:\/\/doi.org\/10.1155\/2019\/8908960","journal-title":"Mediat Inflamm"},{"key":"675_CR78","doi-asserted-by":"crossref","first-page":"110126","DOI":"10.1016\/j.exer.2024.110126","volume":"248","author":"N Zhang","year":"2024","unstructured":"Zhang N, Ji D, Hu Y, et al. The role of nicotinamide riboside in the preservation of retinal ganglion cells using an in vitro glutamate-induced excitotoxicity model. Exp Eye Res. 2024;248:110126. 2024\/10\/17.","journal-title":"Exp Eye Res"},{"key":"675_CR79","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1177\/1535370218794915","volume":"243","author":"R Lenin","year":"2018","unstructured":"Lenin R, Nagy PG, Gentry J, et al. Featured article: deterioration of visual function mediated by senescence-associated endoplasmic reticulum stress in inflammatory tie2-TNF mice. Exp Biol Med (Maywood NJ). 2018;243:976\u201384. https:\/\/doi.org\/10.1177\/1535370218794915.","journal-title":"Exp Biol Med (Maywood NJ)"},{"key":"675_CR80","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8090367","author":"RH Alhasani","year":"2020","unstructured":"Alhasani RH, Almarhoun M, Zhou X, et al. Tauroursodeoxycholic acid protects retinal pigment epithelial cells from oxidative injury and endoplasmic reticulum stress in vitro. Biomedicines. 2020. https:\/\/doi.org\/10.3390\/biomedicines8090367","journal-title":"Biomedicines"},{"key":"675_CR81","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/13510002.2022.2069534","volume":"27","author":"S Zhu","year":"2022","unstructured":"Zhu S, Li X, Dang B, et al. Hydrogen sulfide protects retina from blue light-induced photodamage and degeneration via inhibiting ROS-mediated ER stress-CHOP apoptosis signal. Redox Report: Commun Free Radical Res. 2022;27:100. 110.2022\/04\/29.","journal-title":"Redox Report: Commun Free Radical Res"},{"key":"675_CR82","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020600","author":"GM Tosi","year":"2021","unstructured":"Tosi GM, Giustarini D, Franci L, et al. Superior properties of N-acetylcysteine ethyl ester over N-acetyl cysteine to prevent retinal pigment epithelial cells oxidative damage. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22020600","journal-title":"Int J Mol Sci"},{"key":"675_CR83","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nm.4059","volume":"22","author":"JS Joyal","year":"2016","unstructured":"Joyal JS, Sun Y, Gantner ML, et al. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1. Nat Med. 2016;22:439\u201345. 2016\/03\/15.","journal-title":"Nat Med"},{"key":"675_CR84","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12886-019-1151-9","volume":"19","author":"JL Chen","year":"2019","unstructured":"Chen JL, Hung CT, Keller JJ, et al. Proteomic analysis of retinal pigment epithelium cells after exposure to UVA radiation. BMC Ophthalmol. 2019;19:168. .","journal-title":"BMC Ophthalmol"},{"key":"675_CR85","doi-asserted-by":"crossref","first-page":"e559","DOI":"10.1111\/aos.13995","volume":"97","author":"S De Cill\u00e0","year":"2019","unstructured":"De Cill\u00e0 S, Vezzola D, Farruggio S, et al. The subthreshold micropulse laser treatment of the retina restores the oxidant\/antioxidant balance and counteracts programmed forms of cell death in the mice eyes. Acta Ophthalmol. 2019;97:e559\u201367. 2018\/12\/27.","journal-title":"Acta Ophthalmol"},{"key":"675_CR86","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.4239\/wjd.v14.i9.1349","volume":"14","author":"KX Sun","year":"2023","unstructured":"Sun KX, Chen YY, Li Z, et al. Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway. World J Diabetes. 2023;14:1349\u201368. https:\/\/doi.org\/10.4239\/wjd.v14.i9.1349.","journal-title":"World J Diabetes"},{"key":"675_CR87","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.2174\/0113862073275316231123060640","volume":"27","author":"S Wen","year":"2024","unstructured":"Wen S, Hu M, Chen C, et al. Neuritin alleviates diabetic retinopathy by regulating endoplasmic reticulum stress in rats. Comb Chem High Throughput Screen. 2024;27:2454\u201361. 2024\/01\/04.","journal-title":"Comb Chem High Throughput Screen"},{"key":"675_CR88","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158135","author":"X Zhang","year":"2021","unstructured":"Zhang X, Xu J, Marshall B, et al. The role of caspase-12 in retinal bystander cell death and innate immune responses against MCMV retinitis. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22158135","journal-title":"Int J Mol Sci"},{"key":"675_CR89","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1111\/aos.12113","volume":"92","author":"F Ezquer","year":"2014","unstructured":"Ezquer F, Ezquer M, Arango-Rodriguez M, et al. Could donor multipotent mesenchymal stromal cells prevent or delay the onset of diabetic retinopathy? Acta Ophthalmol. 2014;92:e86\u201395. 2013\/06\/19.","journal-title":"Acta Ophthalmol"},{"key":"675_CR90","doi-asserted-by":"publisher","first-page":"105755","DOI":"10.1016\/j.phrs.2021.105755","volume":"171","author":"CL Zhang","year":"2021","unstructured":"Zhang CL, Wang HL, Li PC, et al. Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy. Pharmacol Res. 2021;171:105755. https:\/\/doi.org\/10.1016\/j.phrs.2021.105755","journal-title":"Pharmacol Res"},{"key":"675_CR91","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.4103\/1673-5374.357913","volume":"18","author":"F Pan","year":"2023","unstructured":"Pan F, Hu D, Sun LJ, et al. Valproate reduces retinal ganglion cell apoptosis in rats after optic nerve crush. Neural Regeneration Res. 2023;18:1607\u201312. https:\/\/doi.org\/10.4103\/1673-5374.357913.","journal-title":"Neural Regeneration Res"},{"key":"675_CR92","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21072351","author":"MC Potilinski","year":"2020","unstructured":"Potilinski MC, Lorenc V, Perisset S, et al. Mechanisms behind retinal ganglion cell loss in diabetes and therapeutic approach. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21072351.","journal-title":"Int J Mol Sci"},{"key":"675_CR93","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41419-019-1780-1","volume":"10","author":"Y Qiu","year":"2019","unstructured":"Qiu Y, Yao J, Jia L, et al. Shifting the balance of autophagy and proteasome activation reduces proteotoxic cell death: a novel therapeutic approach for restoring photoreceptor homeostasis. Cell Death Dis. 2019;10:547. 2019\/07\/20.","journal-title":"Cell Death Dis"},{"key":"675_CR94","doi-asserted-by":"crossref","first-page":"e22641","DOI":"10.1002\/jbt.22641","volume":"35","author":"R Li","year":"2021","unstructured":"Li R, Wang Y, Chen P, et al. Inhibiting endoplasmic reticulum stress by activation of G-protein-coupled Estrogen receptor to protect retinal astrocytes under hyperoxia. J Biochem Mol Toxicol. 2021;35:e22641. 2020\/10\/01.","journal-title":"J Biochem Mol Toxicol"},{"key":"675_CR95","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1167\/iovs.65.11.39","volume":"65","author":"B Kaur","year":"2024","unstructured":"Kaur B, Miglioranza Scavuzzi B, Yang M, et al. ER stress and mitochondrial perturbations regulate cell death in retinal detachment: exploring the role of HIF1\u03b1. Investig Ophthalmol Vis Sci. 2024;65:39. https:\/\/doi.org\/10.1167\/iovs.65.11.39.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"675_CR96","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1177\/11206721211000674","volume":"32","author":"J Wu","year":"2022","unstructured":"Wu J, Cui D, Li H, et al. Protective effects of NAC and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans retinoic acid. Eur J Ophthalmol. 2022;32:395\u2013401. https:\/\/doi.org\/10.1177\/11206721211000674.","journal-title":"Eur J Ophthalmol"},{"key":"675_CR97","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1021\/acs.jafc.5b05864","volume":"64","author":"DD Wang","year":"2016","unstructured":"Wang DD, Zhu HZ, Li SW, et al. Crude saponins of Panax notoginseng have neuroprotective effects to inhibit palmitate-triggered endoplasmic reticulum stress-associated apoptosis and loss of postsynaptic proteins in staurosporine differentiated RGC-5 retinal ganglion cells. J Agric Food Chem. 2016;64:1528\u201339. 2016\/02\/03.","journal-title":"J Agric Food Chem"},{"key":"675_CR98","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/14740338.2021.1952979","volume":"21","author":"DSC Ng","year":"2022","unstructured":"Ng DSC, Ho M, Iu LPL, et al. Safety review of anti-VEGF therapy in patients with myopic choroidal neovascularization. Exp Opin Drug Saf. 2022;21:43\u201354. 2021\/07\/07.","journal-title":"Exp Opin Drug Saf"},{"key":"675_CR99","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.1096\/fj.201700012R","volume":"31","author":"I Grechowa","year":"2017","unstructured":"Grechowa I, Horke S, Wallrath A, et al. Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response. FASEB J: Off Publ Fed Am Soc Exp Biol. 2017;31:3868\u201381. 2017\/05\/17.","journal-title":"FASEB J: Off Publ Fed Am Soc Exp Biol"},{"key":"675_CR100","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1167\/iovs.64.11.17","volume":"64","author":"S Shi","year":"2023","unstructured":"Shi S, Ding C, Zhu S, et al. PERK inhibition suppresses neovascularization and protects neurons during ischemia-induced retinopathy. Investig Ophthalmol Vis Sci. 2023;64:17. https:\/\/doi.org\/10.1167\/iovs.64.11.17","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"675_CR101","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121778","author":"Y Li","year":"2022","unstructured":"Li Y, Li HY, Shao J, et al. GRP75 modulates endoplasmic reticulum-mitochondria coupling and accelerates Ca(2+)-dependent endothelial cell apoptosis in diabetic retinopathy. Biomolecules. 2022. https:\/\/doi.org\/10.3390\/biom12121778","journal-title":"Biomolecules"},{"key":"675_CR102","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3233\/THC-199015","volume":"27","author":"CC Hu","year":"2019","unstructured":"Hu CC, Chiu YC, Chaw JR, et al. Thermo-responsive hydrogel as an anti-VEGF drug delivery system to inhibit retinal angiogenesis in Rex rabbits. Technol Health Care: Official J Eur Soc Eng Med. 2019;27:153\u201363. 2019\/05\/03.","journal-title":"Technol Health Care: Official J Eur Soc Eng Med"},{"key":"675_CR103","doi-asserted-by":"publisher","first-page":"116311","DOI":"10.1016\/j.bcp.2024.116311","volume":"225","author":"J Li","year":"2024","unstructured":"Li J, Zhao T, Sun Y. Interleukin-17A in diabetic retinopathy: the crosstalk of inflammation and angiogenesis. Biochem Pharmacol. 2024;225:116311. https:\/\/doi.org\/10.1016\/j.bcp.2024.116311.","journal-title":"Biochem Pharmacol"},{"key":"675_CR104","doi-asserted-by":"crossref","first-page":"8424","DOI":"10.1167\/iovs.12-10207","volume":"53","author":"A Mima","year":"2012","unstructured":"Mima A, Qi W, Hiraoka-Yamomoto J, et al. Retinal not systemic oxidative and inflammatory stress correlated with VEGF expression in rodent models of insulin resistance and diabetes. Investig Ophthalmol Vis Sci. 2012;53:8424\u201332. 2012\/12\/01.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"675_CR105","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00125-018-4776-y","volume":"62","author":"J Yang","year":"2019","unstructured":"Yang J, Chen C, McLaughlin T, et al. Loss of X-box binding protein 1 in M\u00fcller cells augments retinal inflammation in a mouse model of diabetes. Diabetologia. 2019;62:531\u201343. 2019\/01\/07.","journal-title":"Diabetologia"},{"key":"675_CR106","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9061921","author":"MC Thounaojam","year":"2020","unstructured":"Thounaojam MC, Jadeja RN, Rajpurohit S, et al. Ursodeoxycholic acid halts pathological neovascularization in a mouse model of oxygen-induced retinopathy. J Clin Med. 2020. https:\/\/doi.org\/10.3390\/jcm9061921.","journal-title":"J Clin Med"},{"issue":"Suppl 1","key":"675_CR107","doi-asserted-by":"crossref","first-page":"i11","DOI":"10.1136\/bjophthalmol-2014-305302","volume":"98","author":"D Malik","year":"2014","unstructured":"Malik D, Tarek M, del Caceres J, et al. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture. Br J Ophthalmol. 2014;98(Suppl 1):i11\u201316. 2014\/05\/20.","journal-title":"Br J Ophthalmol"},{"key":"675_CR108","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197413","author":"H Huang","year":"2020","unstructured":"Huang H. Pericyte-endothelial interactions in the retinal microvasculature. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21197413","journal-title":"Int J Mol Sci"},{"key":"675_CR109","doi-asserted-by":"publisher","first-page":"113733","DOI":"10.1016\/j.intimp.2024.113733","volume":"145","author":"W Sun","year":"2025","unstructured":"Sun W, Li X, Zhang L, et al. IL-17A exacerbates synovial inflammation in osteoarthritis via activation of endoplasmic reticulum stress. Int Immunopharmacol. 2025;145:113733. https:\/\/doi.org\/10.1016\/j.intimp.2024.113733.","journal-title":"Int Immunopharmacol"},{"key":"675_CR110","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1080\/13813455.2021.1888302","volume":"129","author":"A Abdel-Ghaffar","year":"2023","unstructured":"Abdel-Ghaffar A, Elhossary GG, Mahmoud AM, et al. Effects of 4-phenylbutyric acid on the development of diabetic retinopathy in diabetic rats: regulation of endoplasmic reticulum stress-oxidative activation. Arch Physiol Biochem. 2023;129:964\u201374. 2021\/03\/04.","journal-title":"Arch Physiol Biochem"},{"key":"675_CR111","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13578-021-00593-6","volume":"11","author":"Y Wang","year":"2021","unstructured":"Wang Y, Gao S, Gao S, et al. Blocking the interaction between interleukin-17A and endoplasmic reticulum stress in macrophage attenuates retinal neovascularization in oxygen-induced retinopathy. Cell Bioscience. 2021;11:82. 2021\/05\/03.","journal-title":"Cell Bioscience"},{"key":"675_CR112","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091023","author":"SH Kim","year":"2019","unstructured":"Kim SH, Kwon D, Lee S, et al. Polyhexamethyleneguanidine phosphate-induced cytotoxicity in liver cells is alleviated by tauroursodeoxycholic acid (TUDCA) via a reduction in endoplasmic reticulum stress. Cells. 2019. https:\/\/doi.org\/10.3390\/cells8091023","journal-title":"Cells"},{"key":"675_CR113","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.2174\/1570159x21666230907152207","volume":"22","author":"J Li","year":"2024","unstructured":"Li J, Huang Z, Jin Y, et al. Neuroprotective effect of Tauroursodeoxycholic acid (TUDCA) on in vitro and in vivo models of retinal disorders: A systematic review. Curr Neuropharmacol. 2024;22:1374\u201390. https:\/\/doi.org\/10.2174\/1570159x21666230907152207.","journal-title":"Curr Neuropharmacol"},{"key":"675_CR114","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1056\/NEJMoa1916945","volume":"383","author":"S Paganoni","year":"2020","unstructured":"Paganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. N Engl J Med. 2020;383:919\u201330. https:\/\/doi.org\/10.1056\/NEJMoa1916945.","journal-title":"N Engl J Med"},{"key":"675_CR115","doi-asserted-by":"crossref","first-page":"108555","DOI":"10.1016\/j.exer.2021.108555","volume":"206","author":"R Janani","year":"2021","unstructured":"Janani R, Anitha RE, Perumal MK, et al. Astaxanthin mediated regulation of VEGF through HIF1\u03b1 and XBP1 signaling pathway: an insight from ARPE-19 cell and streptozotocin mediated diabetic rat model. Exp Eye Res. 2021;206:108555. 2021\/04\/01.","journal-title":"Exp Eye Res"},{"key":"675_CR116","doi-asserted-by":"crossref","first-page":"111730","DOI":"10.1016\/j.jinorgbio.2022.111730","volume":"229","author":"X Wang","year":"2022","unstructured":"Wang X, Hu R, Wang C, et al. Nrf2 axis and endoplasmic reticulum stress mediated autophagy activation is involved in molybdenum and cadmium co-induced hepatotoxicity in ducks. J Inorg Biochem. 2022;229:111730. 2022\/01\/30.","journal-title":"J Inorg Biochem"},{"key":"675_CR117","first-page":"1704","volume":"11","author":"DQ Kong","year":"2018","unstructured":"Kong DQ, Li L, Liu Y, et al. Association between endoplasmic reticulum stress and risk factors of diabetic retinopathy. Int J Ophthalmol. 2018;11:1704\u201310. 2018\/10\/27.","journal-title":"Int J Ophthalmol"},{"key":"675_CR118","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1097\/IAE.0b013e31828bcb2f","volume":"33","author":"L Wu","year":"2013","unstructured":"Wu L, Reply. Correspondence to: intravitreal tumor necrosis factor inhibitors in the treatment of refractory diabetic macular edema: a pilot study from the Pan-American collaborative retina study group. Retina (Philadelphia Pa). 2013;33:1287\u201390. 2013\/04\/30.","journal-title":"Retina (Philadelphia Pa)"},{"key":"675_CR119","doi-asserted-by":"crossref","first-page":"e2941","DOI":"10.1038\/cddis.2017.308","volume":"8","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Lv X, Hu Z, et al. Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction. Cell Death Dis. 2017;8:e2941. 2017\/07\/21.","journal-title":"Cell Death Dis"},{"key":"675_CR120","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3390\/pathophysiology31010007","volume":"31","author":"IA Alvarez","year":"2024","unstructured":"Alvarez IA, Lee M, Eshaq RS, et al. High glucose induces oxidative stress that alters glycocalyx proteoglycan levels in primary rat retinal microvascular endothelial cells and in isolated ophthalmic arteries. Pathophysiology: Official J Int Soc Pathophysiology. 2024;31:89\u201399. https:\/\/doi.org\/10.3390\/pathophysiology31010007.","journal-title":"Pathophysiology: Official J Int Soc Pathophysiology"},{"key":"675_CR121","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3389\/fcell.2017.00099","volume":"5","author":"LJ Campbell","year":"2017","unstructured":"Campbell LJ, Hyde DR. Opportunities for CRISPR\/Cas9 gene editing in retinal regeneration research. Front Cell Dev Biology. 2017;5:99. https:\/\/doi.org\/10.3389\/fcell.2017.00099.","journal-title":"Front Cell Dev Biology"},{"key":"675_CR122","doi-asserted-by":"publisher","DOI":"10.3390\/nu10081046","author":"MK Kang","year":"2018","unstructured":"Kang MK, Lee EJ, Kim YH et al. Chrysin ameliorates malfunction of retinoid visual cycle through blocking activation of AGE-RAGE-ER stress in glucose-stimulated retinal pigment epithelial cells and diabetic eyes. Nutrients. 2018; https:\/\/doi.org\/10.3390\/nu10081046","journal-title":"Nutrients"},{"key":"675_CR123","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.lfs.2019.04.016","volume":"228","author":"H Wang","year":"2019","unstructured":"Wang H, Li J, Zhong P, et al. Blocking CXCR3 with AMG487 ameliorates the blood-retinal barrier disruption in diabetic mice through anti-oxidative. Life Sci. 2019;228:198\u2013207. 2019\/05\/01.","journal-title":"Life Sci"},{"key":"675_CR124","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaf136","author":"S Ge","year":"2025","unstructured":"Ge S, Sun S, Xu H, et al. Deep learning in single-cell and spatial transcriptomics data analysis: advances and challenges from a data science perspective. Brief Bioinform. 2025. https:\/\/doi.org\/10.1093\/bib\/bbaf136","journal-title":"Brief Bioinform"},{"key":"675_CR125","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1007\/s12033-021-00345-4","volume":"63","author":"SA Rasoulinejad","year":"2021","unstructured":"Rasoulinejad SA, Maroufi F. CRISPR-Based genome editing as a new therapeutic tool in retinal diseases. Mol Biotechnol. 2021;63:768\u201379. https:\/\/doi.org\/10.1007\/s12033-021-00345-4.","journal-title":"Mol Biotechnol"}],"container-title":["Biological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40659-026-00675-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-026-00675-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40659-026-00675-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:06:03Z","timestamp":1771596363000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40659-026-00675-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":125,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["675"],"URL":"https:\/\/doi.org\/10.1186\/s40659-026-00675-0","relation":{},"ISSN":["0717-6287"],"issn-type":[{"value":"0717-6287","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"17 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This is a narrative review and did not involve human participants or animal experiments. For research integrity queries, please contact the corresponding author Miss. Shuoyun Weng, Email: shuoyunweng8618@163.com.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}