{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:04:27Z","timestamp":1760241867187,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T00:00:00Z","timestamp":1535673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto","doi-asserted-by":"publisher","award":["Anja ja Mirja Tissarin rahasto"],"award-info":[{"award-number":["Anja ja Mirja Tissarin rahasto"]}],"id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Otto A Malm Foundation","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"The Diabetes Research Foundations","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100013510","name":"Eye and Tissue Bank Foundation","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100013510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Vascular endothelial growth factor (VEGF) expression induces age-related macular degeneration (AMD), which is a common vision-threatening disease due to choroidal neovascularization and a fibrovascular membrane. We describe a mouse model of neovascular AMD with the local expression of human VEGF-A165 in the eye. We use a transgenic mouse in which human VEGF-A165 has been silenced with the loxP-STOP fragment. The choroidal neovascularization and human VEGF-A165 expression in the mouse are induced by subretinal adenoviral Cre gene delivery. Cre gene transfer is compared with adenoviral LacZ gene transfer control. We characterize the AMD phenotype and changes in the vasculature by using fluorescein angiography, optical coherence tomography, and immunohistochemistry. At early time points, mice exhibit increases in retinal thickness (348 \u00b1 114 \u00b5m vs. 231 \u00b1 32 \u00b5m) and choroidal neovascularization area (12000 \u00b1 15174 \u00b5m2 vs. 2169 \u00b1 3495 \u00b5m2) compared with the control. At later time points, choroidal neovascularization develops into subretinal fibrovascular membrane. Human VEGF-A165 expression lasts several weeks. In conclusion, the retinas display vascular abnormalities consistent with choroidal neovascularization. Together with immunohistochemical findings, these changes resemble clinical AMD-like ocular pathologies. We conclude that this mouse model of Cre-induced choroidal neovascularization is useful for mimicking the pathogenesis of AMD, studying the effects of human VEGF-A165 in the retina, and evaluating anti-VEGF treatments for choroidal neovascularization.<\/jats:p>","DOI":"10.3390\/genes9090438","type":"journal-article","created":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T10:57:52Z","timestamp":1535713072000},"page":"438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Human Vascular Endothelial Growth Factor A165 Expression Induces the Mouse Model of Neovascular Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1900-0134","authenticated-orcid":false,"given":"Emmi","family":"Kokki","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70150 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommi","family":"Karttunen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venla","family":"Olsson","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70150 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kati","family":"Kinnunen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland"},{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70029 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-2708","authenticated-orcid":false,"given":"Seppo","family":"Yl\u00e4-Herttuala","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70150 Kuopio, Finland"},{"name":"Heart Center and Gene Therapy Unit, Kuopio University Hospital, 70029 Kuopio, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,31]]},"reference":[{"key":"ref_1","unstructured":"WHO (2017, November 29). Priority Eye Diseases. Available online: http:\/\/www.who.int\/blindness\/causes\/priority\/en\/index7.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1350-9462(02)00043-5","article-title":"Vascular endothelial growth factors and angiogenesis in eye disease","volume":"22","author":"Witmer","year":"2003","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.exer.2005.10.012","article-title":"Mouse models of age-related macular degeneration","volume":"82","author":"Yu","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_4","first-page":"1365","article-title":"Angiogenic gene therapy in cardiovascular diseases: Dream or vision?","volume":"38","author":"Bridges","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.preteyeres.2008.05.001","article-title":"Vascular endothelial growth factor in eye disease","volume":"27","author":"Penn","year":"2008","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s11481-014-9531-7","article-title":"Vascular endothelial growth factor signaling in hypoxia and inflammation","volume":"9","author":"Ramakrishnan","year":"2014","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ajo.2005.10.012","article-title":"Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization","volume":"141","author":"Tong","year":"2006","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1016\/j.ophtha.2009.05.039","article-title":"Neovascular age-related macular degeneration: Intraocular cytokines and growth factors and the influence of therapy with ranibizumab","volume":"116","author":"Funk","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1136\/bjo.81.2.154","article-title":"Increased expression of angiogenic growth factors in age-related maculopathy","volume":"81","author":"Kliffen","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","first-page":"855","article-title":"Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes","volume":"37","author":"Lopez","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1136\/bjo.2003.032466","article-title":"Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy","volume":"88","author":"Matsuoka","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_12","first-page":"1929","article-title":"Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor","volume":"37","author":"Kvanta","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.phrs.2015.11.027","article-title":"Targeting VEGF in eye neovascularization: What\u2019s new?: A comprehensive review on current therapies and oligonucleotide-based interventions under development","volume":"103","author":"Amadio","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.mam.2012.06.003","article-title":"Animal models of age related macular degeneration","volume":"33","author":"Pennesi","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lepp\u00e4nen, P., Kholov\u00e1, I., M\u00e4h\u00f6nen, A.J., Airenne, K., Koota, S., Mansukoski, H., N\u00e4rv\u00e4inen, J., Wirzenius, M., Alhonen, L., and J\u00e4nne, J. (2006). Short and long-term effects of hVEGF-A165 in Cre-activated transgenic mice. PLoS ONE, 1.","DOI":"10.1371\/journal.pone.0000013"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.preteyeres.2016.04.003","article-title":"Risk factors and biomarkers of age-related macular degeneration","volume":"54","author":"Lambert","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1089\/hum.2016.040","article-title":"Advances in gene therapy for diseases of the eye","volume":"27","author":"Petit","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/sj.gt.3300701","article-title":"A vitrectomy improves the transfection efficiency of adenoviral vector-mediated gene transfer to M\u00fcller cells","volume":"5","author":"Sakamoto","year":"1998","journal-title":"Gene Ther."},{"key":"ref_19","first-page":"2535","article-title":"Adenovirus vector-mediated in vivo gene transfer into adult murine retina","volume":"35","author":"Bennett","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","first-page":"2543","article-title":"In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector","volume":"35","author":"Li","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ueyama, K., Mori, K., Shoji, T., Omata, H., Gehlbach, P.L., Brough, D.E., Wei, L.L., and Yoneya, S. (2014). Ocular localization and transduction by adenoviral vectors are serotype-dependent and can be modified by inclusion of RGD fiber modifications. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108071"},{"key":"ref_22","first-page":"59","article-title":"An improved and cost-effective methodology for the reduction of autofluorescence in direct immunofluorescence studies on formalin-fixed paraffin-embedded tissues","volume":"51","author":"Viegas","year":"2007","journal-title":"Eur. J. Histochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.preteyeres.2010.05.003","article-title":"Animal models of choroidal and retinal neovascularization","volume":"29","author":"Grossniklaus","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1021\/nn305958y","article-title":"Targeted intraceptor nanoparticle therapy reduces angiogenesis and fibrosis in primate and murine macular degeneration","volume":"7","author":"Luo","year":"2013","journal-title":"ACS Nano"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00324","DOI":"10.7554\/eLife.00324","article-title":"Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1","volume":"2","author":"Luo","year":"2013","journal-title":"Elife"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1096\/fj.201700336R","article-title":"Animal models of ocular angiogenesis: From development to pathologies","volume":"31","author":"Liu","year":"2017","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1167\/iovs.10-6266","article-title":"In vivo evaluation of laser-induced choroidal neovascularization using spectral-domain optical coherence tomography","volume":"52","author":"Giani","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1006\/exer.2000.0907","article-title":"Quantitative image analysis of laser-induced choroidal neovascularization in rat","volume":"71","author":"Edelman","year":"2000","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.exer.2015.03.009","article-title":"Molecular mechanisms of subretinal fibrosis in age-related macular degeneration","volume":"142","author":"Ishikawa","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11900","DOI":"10.1073\/pnas.0503015102","article-title":"Apolipoprotein E allele-dependent pathogenesis: A model for age-related retinal degeneration","volume":"102","author":"Malek","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/nm950","article-title":"An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice","volume":"9","author":"Ambati","year":"2003","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1097\/IAE.0000000000000819","article-title":"Optical coherence tomography angiography features of subretinal fibrosis in age-related macular degeneration","volume":"35","author":"Miere","year":"2015","journal-title":"Retina"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ophtha.2013.10.019","article-title":"Risk of scar in the comparison of age-related macular degeneration treatments trials","volume":"121","author":"Daniel","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ajo.2013.02.012","article-title":"Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab","volume":"156","author":"Bloch","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1167\/iovs.02-0281","article-title":"AAV-mediated expression of vascular endothelial growth factor induces choroidal neovascularization in rat","volume":"44","author":"Wang","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.1167\/iovs.09-4956","article-title":"A subretinal matrigel rat choroidal neovascularization (CNV) model and inhibition of CNV and associated inflammation and fibrosis by VEGF trap","volume":"51","author":"Cao","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1167\/iovs.07-0870","article-title":"Expression of VLDLR in the retina and evolution of subretinal neovascularization in the knockout mouse model\u2019s retinal angiomatous proliferation","volume":"49","author":"Hu","year":"2008","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhang, H., Yang, Y., Takeda, A., Yoshimura, T., Oshima, Y., Sonoda, K.-H., and Ishibashi, T. (2013). A novel platelet-activating factor receptor antagonist inhibits choroidal neovascularization and subretinal fibrosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068173"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6089","DOI":"10.1167\/iovs.10-5189","article-title":"Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration","volume":"52","author":"Jo","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, Y., Takeda, A., Yoshimura, T., Oshima, Y., Sonoda, K.-H., and Ishibashi, T. (2013). IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080288"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.ajpath.2015.11.014","article-title":"\u03b1B-crystallin regulates subretinal fibrosis by modulation of epithelial-mesenchymal transition","volume":"186","author":"Ishikawa","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1172\/JCI31030","article-title":"Fibrosis and diseases of the eye","volume":"117","author":"Friedlander","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/gt.2008.178","article-title":"Cellular tropism and transduction properties of seven adeno-associated viral vector serotypes in adult retina after intravitreal injection","volume":"16","author":"Ruitenberg","year":"2009","journal-title":"Gene Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1006\/mthe.2001.0473","article-title":"Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa","volume":"4","author":"Liang","year":"2001","journal-title":"Mol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ymthe.2004.09.022","article-title":"Biodistribution of rAAV vectors following intraocular administration: Evidence for the presence and persistence of vector DNA in the optic nerve and in the brain","volume":"11","author":"Provost","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/jgm.1126","article-title":"Novel AAV serotypes for improved ocular gene transfer","volume":"10","author":"Lebherz","year":"2008","journal-title":"J. Gene Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1016\/S0042-6989(98)00308-3","article-title":"Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV","volume":"39","author":"Dudus","year":"1999","journal-title":"Vis. Res."},{"key":"ref_48","first-page":"146","article-title":"Modulation of choroidal neovascularization by subretinal injection of retinal pigment epithelium and polystyrene microbeads","volume":"15","author":"Schmack","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2174\/1566523217666171003170348","article-title":"Comparative study of adeno-associated virus, adenovirus, baculovirus and lentivirus vectors for gene therapy of the eyes","volume":"17","author":"Kalesnykas","year":"2017","journal-title":"Curr. Gene Ther."},{"key":"ref_50","first-page":"1137","article-title":"Differential regulation of a glial fibrillary acidic protein-LacZ transgene in retinal astrocytes and M\u00fcller cells","volume":"36","author":"Verderber","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/eye.2008.206","article-title":"Macrophages in neovascular age-related macular degeneration: Friends or foes?","volume":"23","author":"Skeie","year":"2009","journal-title":"Eye"},{"key":"ref_52","first-page":"119","article-title":"Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization","volume":"8","author":"Grossniklaus","year":"2002","journal-title":"Mol. Vis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1136\/bjo.2009.165563","article-title":"Bruch\u2019s membrane and choroidal macrophages in early and advanced age-related macular degeneration","volume":"94","author":"Cherepanoff","year":"2010","journal-title":"Br. J. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Liu, J., Copland, D.A., Horie, S., Wu, W.-K., Chen, M., Xu, Y., Paul Morgan, B., Mack, M., Xu, H., and Nicholson, L.B. (2013). Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072935"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1167\/iovs.14-13989","article-title":"Spontaneous CNV in a novel mutant mouse is associated with early VEGF-A-driven angiogenesis and late-stage focal edema, neural cell loss, and dysfunction","volume":"55","author":"Nagai","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5934","DOI":"10.1167\/iovs.09-3462","article-title":"The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages","volume":"50","author":"Luhmann","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.exer.2012.11.015","article-title":"Ccl2, Cx3cr1 and Ccl2\/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration","volume":"107","author":"Luhmann","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1474-9726.2007.00351.x","article-title":"Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice","volume":"7","author":"Xu","year":"2008","journal-title":"Aging Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/j.neurobiolaging.2011.03.010","article-title":"Accumulation of murine subretinal macrophages: Effects of age, pigmentation and CX3CR1","volume":"33","author":"Chinnery","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1016\/j.neurobiolaging.2015.05.019","article-title":"Cd59a deficiency in mice leads to preferential innate immune activation in the retinal pigment epithelium\u2013choroid with age","volume":"36","author":"Herrmann","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_61","first-page":"103","article-title":"Accumulation and autofluorescence of phagocytized rod outer segment material in macrophages and microglial cells","volume":"18","author":"Lei","year":"2012","journal-title":"Mol. Vis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/9\/9\/438\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:22:28Z","timestamp":1760196148000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/9\/9\/438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,31]]},"references-count":61,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["genes9090438"],"URL":"https:\/\/doi.org\/10.3390\/genes9090438","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2018,8,31]]}}}