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This response, orchestrated by hypoxia-inducible transcription factors (HIFs), leads to the production of pro-angiogenic factors and plays a critical role in the development and pathogenesis of age-related macular degeneration (AMD). To evaluate the specific contribution of HIF1 to this response we expressed a constitutively active form of HIF1A in rod photoreceptors of the adult mouse retina. This elicited a transcriptional response characterized by the upregulation of genes involved in cell death, inflammation and angiogenesis, all of which play an important role in AMD. The HIF1-mediated response in rods caused severe retinal degeneration, disruption of the RPE and retinal neovascularization. Pathological vessels originated from the deep vascular plexus and penetrated the RPE resembling type 3 macular neovascularization observed in over 20% of patients with neovascular AMD. Our study provides further evidence for the involvement of tissue hypoxia in the pathogenesis of AMD and highlights the potential of HIF1A as a therapeutic target.<\/jats:p>","DOI":"10.1038\/s41419-025-08028-7","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:34:17Z","timestamp":1759732457000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["HIF1 activity in photoreceptors drives type 3 neovascularization and retinal atrophy in a new mouse model of age-related macular degeneration"],"prefix":"10.1038","volume":"16","author":[{"given":"Fredy","family":"Geiger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-8579","authenticated-orcid":false,"given":"Thomas","family":"Heigl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8701-598X","authenticated-orcid":false,"given":"Luca","family":"Merolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Yong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele M.","family":"W\u00f6genstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa P.","family":"Govers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Tsioti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Fottner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0991-4653","authenticated-orcid":false,"given":"Marijana","family":"Samardzija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-4352","authenticated-orcid":false,"given":"Christian","family":"Grimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"8028_CR1","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","volume":"2","author":"WL Wong","year":"2014","unstructured":"Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. 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