{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:35:06Z","timestamp":1787020506676,"version":"build-2736575974"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000915"],"award-info":[{"award-number":["82000915"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101133"],"award-info":[{"award-number":["82101133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670894"],"award-info":[{"award-number":["81670894"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0112701"],"award-info":[{"award-number":["2020YFA0112701"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pearl River Talents Program-Local Innovative and Research Teams","award":["2017BT01S138"],"award-info":[{"award-number":["2017BT01S138"]}]},{"name":"\u201c100 talents plan\u201d from Sun Yat-sen University"},{"name":"the Open Research Funds of the State Key Laboratory of Ophthalmology","award":["2022KF04"],"award-info":[{"award-number":["2022KF04"]}]},{"name":"Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science","award":["2017B030314025"],"award-info":[{"award-number":["2017B030314025"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Age-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn\u2019t been investigated in the pathogenesis of AMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Western blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-\u03b2-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1\u03b1 expression both in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO\n                      <jats:sub>3<\/jats:sub>\n                      in the development of oxidative stress-induced retinal degeneration. Similarly, overexpression of HTRA1 in ARPE-19 cells accelerated cellular senescence. Our RNA-seq revealed an overlap between HTRA1-induced differentially expressed genes associated with aging and those involved in mitochondrial function and hypoxia response in ARPE-19 cells. HTRA1 overexpression in ARPE-19 cells impaired mitochondrial function and augmented glycolytic capacity. Importantly, upregulation of HTRA1 remarkably activated HIF-1 signaling, shown as promoting HIF1\u03b1 expression which mainly located in the nucleus. HIF1\u03b1 translation inhibitor KC7F2 significantly prevented HTRA1-induced cellular senescence in ARPE-19 cells, as well as improved the visual function in hHTRA1-Tg mice treated with NaIO\n                      <jats:sub>3<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-023-01138-9","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T05:02:19Z","timestamp":1686718939000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration"],"prefix":"10.1186","volume":"21","author":[{"given":"Wenchang","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingfang","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bizhi","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehong","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-li","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"issue":"10153","key":"1138_CR1","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","volume":"392","author":"P Mitchell","year":"2018","unstructured":"Mitchell P, et al. Age-related macular degeneration. Lancet. 2018;392(10153):1147\u201359. https:\/\/doi.org\/10.1016\/S0140-6736(18)31550-2.","journal-title":"Lancet"},{"issue":"6","key":"1138_CR2","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1056\/NEJMcp2102061","volume":"385","author":"RS Apte","year":"2021","unstructured":"Apte RS. Age-related Macular Degeneration. N Engl J Med. 2021;385(6):539\u201347. https:\/\/doi.org\/10.1056\/NEJMcp2102061.","journal-title":"N Engl J Med"},{"issue":"2","key":"1138_CR3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/ng.3448","volume":"48","author":"LG Fritsche","year":"2016","unstructured":"Fritsche LG, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016;48(2):134\u201343. https:\/\/doi.org\/10.1038\/ng.3448.","journal-title":"Nat Genet"},{"issue":"6","key":"1138_CR4","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.str.2012.03.021","volume":"20","author":"C Eigenbrot","year":"2012","unstructured":"Eigenbrot C, et al. Structural and functional analysis of HtrA1 and its subdomains. Structure. 2012;20(6):1040\u201350. https:\/\/doi.org\/10.1016\/j.str.2012.03.021.","journal-title":"Structure"},{"issue":"2","key":"1138_CR5","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1534\/genetics.116.195966","volume":"205","author":"F Grassmann","year":"2017","unstructured":"Grassmann F, et al. Recombinant haplotypes narrow the ARMS2\/HTRA1 Association Signal for Age-Related Macular Degeneration. Genetics. 2017;205(2):919\u201324. https:\/\/doi.org\/10.1534\/genetics.116.195966.","journal-title":"Genetics"},{"issue":"5801","key":"1138_CR6","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1126\/science.1133811","volume":"314","author":"Z Yang","year":"2006","unstructured":"Yang Z, et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314(5801):992\u20133. https:\/\/doi.org\/10.1126\/science.1133811.","journal-title":"Science"},{"key":"1138_CR7","unstructured":"Chan CC, et al. Human HtrA1 in the archived eyes with age-related macular degeneration. Trans Am Ophthalmol Soc, 2007. 105: p. 92 \u2013 7; discussion 97 \u2013 8."},{"issue":"1","key":"1138_CR8","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1167\/iovs.16-20922","volume":"58","author":"GM Tosi","year":"2017","unstructured":"Tosi GM, et al. HTRA1 and TGF-beta1 concentrations in the aqueous humor of patients with Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2017;58(1):162\u20137. https:\/\/doi.org\/10.1167\/iovs.16-20922.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"35","key":"1138_CR9","doi-asserted-by":"publisher","first-page":"14578","DOI":"10.1073\/pnas.1102853108","volume":"108","author":"A Jones","year":"2011","unstructured":"Jones A, et al. Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice. Proc Natl Acad Sci U S A. 2011;108(35):14578\u201383. https:\/\/doi.org\/10.1073\/pnas.1102853108.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1138_CR10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.ajo.2021.06.017","volume":"232","author":"AM Khanani","year":"2021","unstructured":"Khanani AM, et al. Phase 1 study of the Anti-HtrA1 antibody-binding Fragment FHTR2163 in Geographic Atrophy secondary to age-related Macular Degeneration. Am J Ophthalmol. 2021;232:49\u201357. https:\/\/doi.org\/10.1016\/j.ajo.2021.06.017.","journal-title":"Am J Ophthalmol"},{"issue":"18","key":"1138_CR11","doi-asserted-by":"publisher","first-page":"9952","DOI":"10.1073\/pnas.1917608117","volume":"117","author":"I Tom","year":"2020","unstructured":"Tom I, et al. Development of a therapeutic anti-HtrA1 antibody and the identification of DKK3 as a pharmacodynamic biomarker in geographic atrophy. Proc Natl Acad Sci U S A. 2020;117(18):9952\u201363. https:\/\/doi.org\/10.1073\/pnas.1917608117.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"1138_CR12","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.mehy.2012.01.018","volume":"78","author":"MR Kozlowski","year":"2012","unstructured":"Kozlowski MR. RPE cell senescence: a key contributor to age-related macular degeneration. Med Hypotheses. 2012;78(4):505\u201310. https:\/\/doi.org\/10.1016\/j.mehy.2012.01.018.","journal-title":"Med Hypotheses"},{"issue":"1","key":"1138_CR13","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12974-021-02088-0","volume":"18","author":"KS Lee","year":"2021","unstructured":"Lee KS, et al. Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration. J Neuroinflammation. 2021;18(1):32. https:\/\/doi.org\/10.1186\/s12974-021-02088-0.","journal-title":"J Neuroinflammation"},{"key":"1138_CR14","doi-asserted-by":"publisher","unstructured":"Ahamed W, et al. HTRA1 regulates subclinical inflammation and activates proangiogenic response in the retina and choroid. Int J Mol Sci. 2022;23(18). https:\/\/doi.org\/10.3390\/ijms231810206.","DOI":"10.3390\/ijms231810206"},{"issue":"3\u20134","key":"1138_CR15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41434-021-00281-7","volume":"29","author":"S Visuvanathan","year":"2022","unstructured":"Visuvanathan S, et al. XIAP gene therapy effects on retinal ganglion cell structure and function in a mouse model of glaucoma. Gene Ther. 2022;29(3\u20134):147\u201356. https:\/\/doi.org\/10.1038\/s41434-021-00281-7.","journal-title":"Gene Ther"},{"issue":"4","key":"1138_CR16","doi-asserted-by":"publisher","first-page":"e61381","DOI":"10.1371\/journal.pone.0061381","volume":"8","author":"M Chen","year":"2013","unstructured":"Chen M, et al. Age- and light-dependent development of localised retinal atrophy in CCL2(-\/-)CX3CR1(GFP\/GFP) mice. PLoS ONE. 2013;8(4):e61381. https:\/\/doi.org\/10.1371\/journal.pone.0061381.","journal-title":"PLoS ONE"},{"key":"1138_CR17","doi-asserted-by":"publisher","unstructured":"Dunn KC, et al. ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp Eye Res. 1996;62(2). https:\/\/doi.org\/10.1006\/exer.1996.0020. 155 \u2013 69.","DOI":"10.1006\/exer.1996.0020"},{"issue":"7","key":"1138_CR18","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1038\/nprot.2016.065","volume":"11","author":"R Fernandez-Godino","year":"2016","unstructured":"Fernandez-Godino R, Garland DL, Pierce EA. Isolation, culture and characterization of primary mouse RPE cells. Nat Protoc. 2016;11(7):1206\u201318. https:\/\/doi.org\/10.1038\/nprot.2016.065.","journal-title":"Nat Protoc"},{"key":"1138_CR19","doi-asserted-by":"publisher","first-page":"788422","DOI":"10.3389\/fcell.2021.788422","volume":"9","author":"M Zhao","year":"2021","unstructured":"Zhao M, et al. Defect of LSS disrupts Lens Development in Cataractogenesis. Front Cell Dev Biol. 2021;9:788422. https:\/\/doi.org\/10.3389\/fcell.2021.788422.","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"1138_CR20","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1167\/iovs.13-13075","volume":"55","author":"J Wang","year":"2014","unstructured":"Wang J, et al. Direct effect of sodium iodate on neurosensory retina. Invest Ophthalmol Vis Sci. 2014;55(3):1941\u201353. https:\/\/doi.org\/10.1167\/iovs.13-13075.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1138_CR21","doi-asserted-by":"publisher","unstructured":"Koster C, et al. Sodium-Iodate Injection Can replicate retinal degenerative Disease Stages in pigmented mice and Rats: non-invasive Follow-Up using OCT and ERG. Int J Mol Sci. 2022;23(6). https:\/\/doi.org\/10.3390\/ijms23062918.","DOI":"10.3390\/ijms23062918"},{"key":"1138_CR22","doi-asserted-by":"publisher","unstructured":"Moiseeva O, et al. Mitochondrial dysfunction contributes to oncogene-induced senescence. Mol Cell Biol. 2009;29(16). https:\/\/doi.org\/10.1128\/MCB.01868-08. 4495 \u2013 507.","DOI":"10.1128\/MCB.01868-08"},{"issue":"2","key":"1138_CR23","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.cmet.2015.11.011","volume":"23","author":"CD Wiley","year":"2016","unstructured":"Wiley CD, et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 2016;23(2):303\u201314. https:\/\/doi.org\/10.1016\/j.cmet.2015.11.011.","journal-title":"Cell Metab"},{"issue":"7","key":"1138_CR24","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrrheum.2016.69","volume":"12","author":"U Fearon","year":"2016","unstructured":"Fearon U, et al. Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis. Nat Rev Rheumatol. 2016;12(7):385\u201397. https:\/\/doi.org\/10.1038\/nrrheum.2016.69.","journal-title":"Nat Rev Rheumatol"},{"key":"1138_CR25","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2021.4601","author":"V Kuan","year":"2021","unstructured":"Kuan V, et al. Association of Smoking, Alcohol Consumption, blood pressure, body Mass Index, and glycemic risk factors with age-related Macular Degeneration: a mendelian randomization study. JAMA Ophthalmol. 2021. https:\/\/doi.org\/10.1001\/jamaophthalmol.2021.4601.","journal-title":"JAMA Ophthalmol"},{"key":"1138_CR26","doi-asserted-by":"publisher","first-page":"16016","DOI":"10.1038\/sigtrans.2016.16","volume":"1","author":"W Wang","year":"2016","unstructured":"Wang W, et al. Genetic and environmental factors strongly influence risk, severity and progression of age-related macular degeneration. Signal Transduct Target Ther. 2016;1:16016. https:\/\/doi.org\/10.1038\/sigtrans.2016.16.","journal-title":"Signal Transduct Target Ther"},{"key":"1138_CR27","doi-asserted-by":"publisher","unstructured":"Abokyi S, et al. Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models Oxid Med Cell Longev, 2020. 2020: p.\u00a07901270. https:\/\/doi.org\/10.1155\/2020\/7901270.","DOI":"10.1155\/2020\/7901270"},{"key":"1138_CR28","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","volume":"60","author":"S Datta","year":"2017","unstructured":"Datta S, et al. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res. 2017;60:201\u201318. https:\/\/doi.org\/10.1016\/j.preteyeres.2017.03.002.","journal-title":"Prog Retin Eye Res"},{"key":"1138_CR29","doi-asserted-by":"publisher","first-page":"757","DOI":"10.2147\/CIA.S158513","volume":"13","author":"I Liguori","year":"2018","unstructured":"Liguori I, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757\u201372. https:\/\/doi.org\/10.2147\/CIA.S158513.","journal-title":"Clin Interv Aging"},{"issue":"13","key":"1138_CR30","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1002\/1873-3468.13498","volume":"593","author":"J Chapman","year":"2019","unstructured":"Chapman J, Fielder E, Passos JF. Mitochondrial dysfunction and cell senescence: deciphering a complex relationship. FEBS Lett. 2019;593(13):1566\u201379. https:\/\/doi.org\/10.1002\/1873-3468.13498.","journal-title":"FEBS Lett"},{"key":"1138_CR31","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.exer.2013.04.013","volume":"112","author":"Supanji","year":"2013","unstructured":"Supanji, et al. HtrA1 is induced by oxidative stress and enhances cell senescence through p38 MAPK pathway. Exp Eye Res. 2013;112:79\u201392. https:\/\/doi.org\/10.1016\/j.exer.2013.04.013.","journal-title":"Exp Eye Res"},{"issue":"8","key":"1138_CR32","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1021\/acs.jproteome.8b00129","volume":"17","author":"J Schillinger","year":"2018","unstructured":"Schillinger J, et al. HTRA1-Dependent cell cycle proteomics. J Proteome Res. 2018;17(8):2679\u201394. https:\/\/doi.org\/10.1021\/acs.jproteome.8b00129.","journal-title":"J Proteome Res"},{"key":"1138_CR33","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s12885-016-2425-8","volume":"16","author":"N Schmidt","year":"2016","unstructured":"Schmidt N, et al. Epigenetic silencing of serine protease HTRA1 drives polyploidy. BMC Cancer. 2016;16:399. https:\/\/doi.org\/10.1186\/s12885-016-2425-8.","journal-title":"BMC Cancer"},{"key":"1138_CR34","doi-asserted-by":"publisher","first-page":"768026","DOI":"10.1155\/2014\/768026","volume":"2014","author":"J Blasiak","year":"2014","unstructured":"Blasiak J, et al. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration. Biomed Res Int. 2014;2014:768026. https:\/\/doi.org\/10.1155\/2014\/768026.","journal-title":"Biomed Res Int"},{"key":"1138_CR35","doi-asserted-by":"publisher","unstructured":"Kurihara T, et al. Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration. Elife. 2016;5. https:\/\/doi.org\/10.7554\/eLife.14319.","DOI":"10.7554\/eLife.14319"},{"issue":"1","key":"1138_CR36","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.preteyeres.2010.09.003","volume":"30","author":"E Stefansson","year":"2011","unstructured":"Stefansson E, Geirsdottir A, Sigurdsson H. Metabolic physiology in age related macular degeneration. Prog Retin Eye Res. 2011;30(1):72\u201380. https:\/\/doi.org\/10.1016\/j.preteyeres.2010.09.003.","journal-title":"Prog Retin Eye Res"},{"issue":"5","key":"1138_CR37","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1158\/1541-7786.MCR-11-0065","volume":"9","author":"SM Welford","year":"2011","unstructured":"Welford SM, Giaccia AJ. Hypoxia and senescence: the impact of oxygenation on tumor suppression. Mol Cancer Res. 2011;9(5):538\u201344. https:\/\/doi.org\/10.1158\/1541-7786.MCR-11-0065.","journal-title":"Mol Cancer Res"},{"issue":"6","key":"1138_CR38","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1007\/s11357-021-00457-4","volume":"43","author":"JB Chae","year":"2021","unstructured":"Chae JB, et al. Targeting senescent retinal pigment epithelial cells facilitates retinal regeneration in mouse models of age-related macular degeneration. Geroscience. 2021;43(6):2809\u201333. https:\/\/doi.org\/10.1007\/s11357-021-00457-4.","journal-title":"Geroscience"},{"issue":"1","key":"1138_CR39","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/clpt.2012.193","volume":"93","author":"RM Naylor","year":"2013","unstructured":"Naylor RM, Baker DJ, van Deursen JM. Senescent cells: a novel therapeutic target for aging and age-related diseases. Clin Pharmacol Ther. 2013;93(1):105\u201316. https:\/\/doi.org\/10.1038\/clpt.2012.193.","journal-title":"Clin Pharmacol Ther"},{"key":"1138_CR40","doi-asserted-by":"publisher","unstructured":"Zhang L, et al. Cellular senescence: a key therapeutic target in aging and diseases. J Clin Invest. 2022;132(15). https:\/\/doi.org\/10.1172\/JCI158450.","DOI":"10.1172\/JCI158450"},{"issue":"17","key":"1138_CR41","doi-asserted-by":"publisher","first-page":"6021","DOI":"10.1073\/pnas.0501823102","volume":"102","author":"S Grau","year":"2005","unstructured":"Grau S, et al. Implications of the serine protease HtrA1 in amyloid precursor protein processing. Proc Natl Acad Sci U S A. 2005;102(17):6021\u20136. https:\/\/doi.org\/10.1073\/pnas.0501823102.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1138_CR42","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.exger.2016.03.019","volume":"81","author":"M Lorenzi","year":"2016","unstructured":"Lorenzi M, et al. Association of frailty with the serine protease HtrA1 in older adults. Exp Gerontol. 2016;81:8\u201312. https:\/\/doi.org\/10.1016\/j.exger.2016.03.019.","journal-title":"Exp Gerontol"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-023-01138-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-023-01138-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-023-01138-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T05:03:52Z","timestamp":1686719032000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-023-01138-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,14]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1138"],"URL":"https:\/\/doi.org\/10.1186\/s12964-023-01138-9","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,14]]},"assertion":[{"value":"14 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the animal procedures were approved by the Animal Ethical Committee at Zhongshan Ophthalmic Center, Sun Yat-sen University (Guangzhou, China), and all the uses of animals were performed in accordance with the Association for Research in Vision and Ophthalmology (ARVO) statement.","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 no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"134"}}