{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:31:27Z","timestamp":1777401087015,"version":"3.51.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["N000250\/1"],"award-info":[{"award-number":["N000250\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["N000250\/1"],"award-info":[{"award-number":["N000250\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["N000250\/1"],"award-info":[{"award-number":["N000250\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["N000250\/1"],"award-info":[{"award-number":["N000250\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["N000250\/1"],"award-info":[{"award-number":["N000250\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["N000250\/1"],"award-info":[{"award-number":["N000250\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Age related macular degeneration (AMD) is the most common blinding disease in those over 60 years. In 50% of cases it is associated with polymorphisms of complement factor H (FH), implicating immune vulnerability. But such individuals may exhibit abnormal outer retinal blood flow decades before disease initiation, suggesting an early disease footprint. FH is expressed in the retinal pigmented epithelium (RPE). During development the RPE is adjacent to the site of retinal mitosis and complex regulatory interactions occur between the relatively mature RPE and retinal neuronal precursors that control the cell cycle. Here we ask if the absence of FH from the RPE influences retinal development using a mouse CFH knockout (<jats:italic>Cfh<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) with an aged retinal degenerative phenotype. We reveal that from birth, these mice have significantly disrupted and delayed retinal development. However, once development is complete, their retinae appear relatively normal, although many photoreceptor and RPE mitochondria are abnormally large, suggesting dysfunction consistent with premature ATP decline in <jats:italic>Cfh<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>. Total retinal mtDNA is also reduced and these deficits are associated shortly after with reduced retinal function. <jats:italic>Cfh<\/jats:italic><jats:sup>\u2212\/+<\/jats:sup> mice also show significant abnormal patterns of cell production but not as great as in <jats:italic>Cfh<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>. These results reveal that not only is FH an important player in sculpting retinal development but also that the developmental abnormality in <jats:italic>Cfh<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> likely establishes critical vulnerability for later aged retinal degeneration.<\/jats:p>","DOI":"10.1038\/s41598-018-37673-6","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T11:04:33Z","timestamp":1548932673000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration"],"prefix":"10.1038","volume":"9","author":[{"given":"Chrishne","family":"Sivapathasuntharam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew John","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harpreet","family":"Shinhmar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaimie Hoh","family":"Kam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sobha","family":"Sivaprasad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-4521","authenticated-orcid":false,"given":"Glen","family":"Jeffery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"37673_CR1","doi-asserted-by":"crossref","unstructured":"Curcio, C. A. & Johnson, M. Structure, Function, and Pathology of Bruch\u2019s Membrane. 5th edn, Vol. 1, 465\u2013481 (Elsevier Inc 2012).","DOI":"10.1016\/B978-1-4557-0737-9.00020-5"},{"key":"37673_CR2","first-page":"3117","volume":"41","author":"RA Linsenmeier","year":"2000","unstructured":"Linsenmeier, R. A. & Padnick-Silver, L. Metabolic dependence of photoreceptors on the choroid in the normal and detached retina. Invest Ophthalmol Vis Sci 41, 3117\u20133123 (2000).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"37673_CR3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1017\/S0952523802194028","volume":"19","author":"QV Hoang","year":"2002","unstructured":"Hoang, Q. V., Linsenmeier, R. A., Chung, C. K. & Curcio, C. A. Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation. Vis Neurosci 19, 395\u2013407 (2002).","journal-title":"Vis Neurosci"},{"key":"37673_CR4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S1350-9462(98)00012-3","volume":"18","author":"R Guymer","year":"1999","unstructured":"Guymer, R., Luthert, P. & Bird, A. Changes in Bruch\u2019s membrane and related structures with age. Prog Retin Eye Res 18, 59\u201390 (1999).","journal-title":"Prog Retin Eye Res"},{"key":"37673_CR5","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1016\/j.neurobiolaging.2008.10.019","volume":"31","author":"AL Wang","year":"2010","unstructured":"Wang, A. L., Lukas, T. J., Yuan, M. & Neufeld, A. H. Age-related increase in mitochondrial DNA damage and loss of DNA repair capacity in the neural retina. Neurobiol Aging 31, 2002\u20132010, https:\/\/doi.org\/10.1016\/j.neurobiolaging.2008.10.019 (2010).","journal-title":"Neurobiol Aging"},{"key":"37673_CR6","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1038\/nm.3998","volume":"21","author":"T Finkel","year":"2015","unstructured":"Finkel, T. The metabolic regulation of aging. Nat Med 21, 1416\u20131423, https:\/\/doi.org\/10.1038\/nm.3998 (2015).","journal-title":"Nat Med"},{"key":"37673_CR7","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C Lopez-Otin","year":"2013","unstructured":"Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194\u20131217, https:\/\/doi.org\/10.1016\/j.cell.2013.05.039 (2013).","journal-title":"Cell"},{"key":"37673_CR8","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1017\/S0952523807070204","volume":"24","author":"A Cunea","year":"2007","unstructured":"Cunea, A. & Jeffery, G. The ageing photoreceptor. Vis Neurosci 24, 151\u2013155, https:\/\/doi.org\/10.1017\/S0952523807070204 (2007).","journal-title":"Vis Neurosci"},{"key":"37673_CR9","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/ana.410330305","volume":"33","author":"CA Curcio","year":"1993","unstructured":"Curcio, C. A. & Drucker, D. N. Retinal ganglion cells in Alzheimer\u2019s disease and aging. Ann Neurol 33, 248\u2013257, https:\/\/doi.org\/10.1002\/ana.410330305 (1993).","journal-title":"Ann Neurol"},{"key":"37673_CR10","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1126\/science.1110189","volume":"308","author":"AO Edwards","year":"2005","unstructured":"Edwards, A. O. et al. Complement factor H polymorphism and age-related macular degeneration. Science 308, 421\u2013424, https:\/\/doi.org\/10.1126\/science.1110189 (2005).","journal-title":"Science"},{"key":"37673_CR11","doi-asserted-by":"publisher","first-page":"7227","DOI":"10.1073\/pnas.0501536102","volume":"102","author":"GS Hageman","year":"2005","unstructured":"Hageman, G. S. et al. A common haplotype in the complement regulatory gene factor H (HF1\/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 102, 7227\u20137232, https:\/\/doi.org\/10.1073\/pnas.0501536102 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"37673_CR12","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1126\/science.1109557","volume":"308","author":"RJ Klein","year":"2005","unstructured":"Klein, R. J. et al. Complement factor H polymorphism in age-related macular degeneration. Science 308, 385\u2013389, https:\/\/doi.org\/10.1126\/science.1109557 (2005).","journal-title":"Science"},{"key":"37673_CR13","doi-asserted-by":"publisher","first-page":"4091","DOI":"10.1167\/iovs.05-1655","volume":"47","author":"MN Mandal","year":"2006","unstructured":"Mandal, M. N. & Ayyagari, R. Complement factor H: spatial and temporal expression and localization in the eye. Invest Ophthalmol Vis Sci 47, 4091\u20134097, https:\/\/doi.org\/10.1167\/iovs.05-1655 (2006).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"37673_CR14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.preteyeres.2017.09.001","volume":"62","author":"CB Toomey","year":"2018","unstructured":"Toomey, C. B., Johnson, L. V. & Bowes Rickman, C. Complement factor H in AMD: Bridging genetic associations and pathobiology. Prog Retin Eye Res 62, 38\u201357, https:\/\/doi.org\/10.1016\/j.preteyeres.2017.09.001 (2018).","journal-title":"Prog Retin Eye Res"},{"key":"37673_CR15","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/jcm4010018","volume":"4","author":"SJ Clark","year":"2015","unstructured":"Clark, S. J. & Bishop, P. N. Role of Factor H and Related Proteins in Regulating Complement Activation in the Macula, and Relevance to Age-Related Macular Degeneration. J Clin Med 4, 18\u201331, https:\/\/doi.org\/10.3390\/jcm4010018 (2015).","journal-title":"J Clin Med"},{"key":"37673_CR16","first-page":"277","volume":"7","author":"S Zhao","year":"2001","unstructured":"Zhao, S. & Overbeek, P. A. Regulation of choroid development by the retinal pigment epithelium. Mol Vis 7, 277\u2013282 (2001).","journal-title":"Mol Vis"},{"key":"37673_CR17","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1016\/S0002-9440(10)61231-X","volume":"167","author":"AG Marneros","year":"2005","unstructured":"Marneros, A. G. et al. Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol 167, 1451\u20131459, https:\/\/doi.org\/10.1016\/S0002-9440(10)61231-X (2005).","journal-title":"Am J Pathol"},{"key":"37673_CR18","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ydbio.2010.08.006","volume":"347","author":"H Thompson","year":"2010","unstructured":"Thompson, H., Griffiths, J. S., Jeffery, G. & McGonnell, I. M. The retinal pigment epithelium of the eye regulates the development of scleral cartilage. Dev Biol 347, 40\u201352, https:\/\/doi.org\/10.1016\/j.ydbio.2010.08.006 (2010).","journal-title":"Dev Biol"},{"key":"37673_CR19","first-page":"193","volume":"81","author":"RW Young","year":"1983","unstructured":"Young, R. W. The ninth Frederick H. Verhoeff lecture. The life history of retinal cells. Trans Am Ophthalmol Soc 81, 193\u2013228 (1983).","journal-title":"Trans Am Ophthalmol Soc"},{"key":"37673_CR20","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/(SICI)1096-9861(19990315)405:3<394::AID-CNE9>3.0.CO;2-Y","volume":"405","author":"M Ilia","year":"1999","unstructured":"Ilia, M. & Jeffery, G. Retinal mitosis is regulated by dopa, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae. J Comp Neurol 405, 394\u2013405 (1999).","journal-title":"J Comp Neurol"},{"key":"37673_CR21","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/cne.21388","volume":"503","author":"MS Tibber","year":"2007","unstructured":"Tibber, M. S., Becker, D. & Jeffery, G. Levels of transient gap junctions between the retinal pigment epithelium and the neuroblastic retina are influenced by catecholamines and correlate with patterns of cell production. J Comp Neurol 503, 128\u2013134, https:\/\/doi.org\/10.1002\/cne.21388 (2007).","journal-title":"J Comp Neurol"},{"key":"37673_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1172\/JCI86418","volume":"127","author":"LS Keir","year":"2017","unstructured":"Keir, L. S. et al. VEGF regulates local inhibitory complement proteins in the eye and kidney. J Clin Invest 127, 199\u2013214, https:\/\/doi.org\/10.1172\/JCI86418 (2017).","journal-title":"J Clin Invest"},{"key":"37673_CR23","doi-asserted-by":"publisher","first-page":"e60424","DOI":"10.1371\/journal.pone.0060424","volume":"8","author":"R Told","year":"2013","unstructured":"Told, R. et al. Alterations of choroidal blood flow regulation in young healthy subjects with complement factor H polymorphism. PLoS One 8, e60424, https:\/\/doi.org\/10.1371\/journal.pone.0060424 (2013).","journal-title":"PLoS One"},{"key":"37673_CR24","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.exer.2015.09.003","volume":"146","author":"KR Chirco","year":"2016","unstructured":"Chirco, K. R., Tucker, B. A., Stone, E. M. & Mullins, R. F. Selective accumulation of the complement membrane attack complex in aging choriocapillaris. Exp Eye Res 146, 393\u2013397, https:\/\/doi.org\/10.1016\/j.exer.2015.09.003 (2016).","journal-title":"Exp Eye Res"},{"key":"37673_CR25","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.exer.2011.06.015","volume":"93","author":"RF Mullins","year":"2011","unstructured":"Mullins, R. F. et al. Elevated membrane attack complex in human choroid with high risk complement factor H genotypes. Exp Eye Res 93, 565\u2013567, https:\/\/doi.org\/10.1016\/j.exer.2011.06.015 (2011).","journal-title":"Exp Eye Res"},{"key":"37673_CR26","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1146\/annurev-neuro-061010-113810","volume":"35","author":"AH Stephan","year":"2012","unstructured":"Stephan, A. H., Barres, B. A. & Stevens, B. The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 35, 369\u2013389, https:\/\/doi.org\/10.1146\/annurev-neuro-061010-113810 (2012).","journal-title":"Annu Rev Neurosci"},{"key":"37673_CR27","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1016\/j.neurobiolaging.2015.06.010","volume":"36","author":"KC Calaza","year":"2015","unstructured":"Calaza, K. C., Kam, J. H., Hogg, C. & Jeffery, G. Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light. Neurobiol Aging 36, 2869\u20132876, https:\/\/doi.org\/10.1016\/j.neurobiolaging.2015.06.010 (2015).","journal-title":"Neurobiol Aging"},{"key":"37673_CR28","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.brainres.2007.10.083","volume":"1189","author":"J Stone","year":"2008","unstructured":"Stone, J., van Driel, D., Valter, K., Rees, S. & Provis, J. The locations of mitochondria in mammalian photoreceptors: relation to retinal vasculature. Brain Res 1189, 58\u201369, https:\/\/doi.org\/10.1016\/j.brainres.2007.10.083 (2008).","journal-title":"Brain Res"},{"key":"37673_CR29","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/cne.901880204","volume":"188","author":"LD Carter-Dawson","year":"1979","unstructured":"Carter-Dawson, L. D. & LaVail, M. M. Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy. J Comp Neurol 188, 245\u2013262, https:\/\/doi.org\/10.1002\/cne.901880204 (1979).","journal-title":"J Comp Neurol"},{"key":"37673_CR30","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.exer.2016.07.002","volume":"149","author":"J Hoh Kam","year":"2016","unstructured":"Hoh Kam, J., Morgan, J. E. & Jeffery, G. Aged complement factor H knockout mice kept in a clean barriered environment have reduced retinal pathology. Exp Eye Res 149, 116\u2013125, https:\/\/doi.org\/10.1016\/j.exer.2016.07.002 (2016).","journal-title":"Exp Eye Res"},{"key":"37673_CR31","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/S0960-9822(95)00255-7","volume":"5","author":"SM Raymond","year":"1995","unstructured":"Raymond, S. M. & Jackson, I. J. The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina. Curr Biol 5, 1286\u20131295 (1995).","journal-title":"Curr Biol"},{"key":"37673_CR32","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/0039-6257(85)90077-3","volume":"30","author":"PE Kinnear","year":"1985","unstructured":"Kinnear, P. E., Jay, B. & Witkop, C. J. Jr. Albinism. Surv Ophthalmol 30, 75\u2013101 (1985).","journal-title":"Surv Ophthalmol"},{"key":"37673_CR33","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/cne.20920","volume":"496","author":"MS Tibber","year":"2006","unstructured":"Tibber, M. S., Whitmore, A. V. & Jeffery, G. Cell division and cleavage orientation in the developing retina are regulated by L-DOPA. J Comp Neurol 496, 369\u2013381, https:\/\/doi.org\/10.1002\/cne.20920 (2006).","journal-title":"J Comp Neurol"},{"key":"37673_CR34","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nri2975","volume":"11","author":"AP West","year":"2011","unstructured":"West, A. P., Shadel, G. S. & Ghosh, S. Mitochondria in innate immune responses. Nat Rev Immunol 11, 389\u2013402, https:\/\/doi.org\/10.1038\/nri2975 (2011).","journal-title":"Nat Rev Immunol"},{"key":"37673_CR35","doi-asserted-by":"publisher","first-page":"817","DOI":"10.3892\/ijmm.2014.1650","volume":"33","author":"JZ Zhang","year":"2014","unstructured":"Zhang, J. Z., Liu, Z., Liu, J., Ren, J. X. & Sun, T. S. Mitochondrial DNA induces inflammation and increases TLR9\/NF-kappaB expression in lung tissue. Int J Mol Med 33, 817\u2013824, https:\/\/doi.org\/10.3892\/ijmm.2014.1650 (2014).","journal-title":"Int J Mol Med"},{"key":"37673_CR36","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature08780","volume":"464","author":"Q Zhang","year":"2010","unstructured":"Zhang, Q. et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464, 104\u2013107, https:\/\/doi.org\/10.1038\/nature08780 (2010).","journal-title":"Nature"},{"key":"37673_CR37","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","volume":"131","author":"B Stevens","year":"2007","unstructured":"Stevens, B. et al. The classical complement cascade mediates CNS synapse elimination. Cell 131, 1164\u20131178, https:\/\/doi.org\/10.1016\/j.cell.2007.10.036 (2007).","journal-title":"Cell"},{"key":"37673_CR38","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/bs.ai.2017.06.004","volume":"135","author":"J Presumey","year":"2017","unstructured":"Presumey, J., Bialas, A. R. & Carroll, M. C. Complement System in Neural Synapse Elimination in Development and Disease. Adv Immunol 135, 53\u201379, https:\/\/doi.org\/10.1016\/bs.ai.2017.06.004 (2017).","journal-title":"Adv Immunol"},{"key":"37673_CR39","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0165-3806(84)90079-8","volume":"315","author":"G Jeffery","year":"1984","unstructured":"Jeffery, G. Retinal ganglion cell death and terminal field retraction in the developing rodent visual system. Brain Res 315, 81\u201396 (1984).","journal-title":"Brain Res"},{"key":"37673_CR40","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1002\/cne.902670405","volume":"267","author":"SR Robinson","year":"1988","unstructured":"Robinson, S. R. Cell death in the inner and outer nuclear layers of the developing cat retina. J Comp Neurol 267, 507\u2013515, https:\/\/doi.org\/10.1002\/cne.902670405 (1988).","journal-title":"J Comp Neurol"},{"key":"37673_CR41","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/35053522","volume":"2","author":"FJ Livesey","year":"2001","unstructured":"Livesey, F. J. & Cepko, C. L. Vertebrate neural cell-fate determination: lessons from the retina. Nat Rev Neurosci 2, 109\u2013118, https:\/\/doi.org\/10.1038\/35053522 (2001).","journal-title":"Nat Rev Neurosci"},{"key":"37673_CR42","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.ajpath.2013.04.008","volume":"183","author":"J Hoh Kam","year":"2013","unstructured":"Hoh Kam, J., Lenassi, E., Malik, T. H., Pickering, M. C. & Jeffery, G. Complement component C3 plays a critical role in protecting the aging retina in a murine model of age-related macular degeneration. Am J Pathol 183, 480\u2013492, https:\/\/doi.org\/10.1016\/j.ajpath.2013.04.008 (2013).","journal-title":"Am J Pathol"},{"key":"37673_CR43","doi-asserted-by":"publisher","first-page":"412","DOI":"10.2353\/ajpath.2009.080927","volume":"175","author":"P Lundh von Leithner","year":"2009","unstructured":"Lundh von Leithner, P. et al. Complement factor h is critical in the maintenance of retinal perfusion. Am J Pathol 175, 412\u2013421, https:\/\/doi.org\/10.2353\/ajpath.2009.080927 (2009).","journal-title":"Am J Pathol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37673-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37673-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37673-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T05:23:49Z","timestamp":1671254629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-37673-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,31]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["37673"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-37673-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,31]]},"assertion":[{"value":"3 September 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1082"}}