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Wnt inhibitor factor 1 (WIF1) is a secreted Wnt antagonist that regulates angiogenesis. However, the significance of WIF1 in RNV associated disease has not been explicitly tested. In our study, we found that the WIF1 expressions were strongly downregulated in the vitreous of proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). Similarly, retinal WIF1 expression was significantly downregulated in OIR mice, relative to normal mice at P17. After injection of WIF1 overexpression lentivirus into the vitreous of OIR mice, overexpressing WIF1 in OIR mice vitreous strongly reduced avascular areas and neovascular tufts, increased vessel branches, raised a\u2010, b\u2010waves and oscillatory potentials amplitudes on ERG, increased retinal thickness and the number of synapses in retina, normalized the Golgi, mitochondria, and outer segments of photoreceptors. Furthermore, overexpression WIF1 suppressed expressions of \u03b2\u2010catenin, vascular endothelial growth factor (VEGF), p\u2010AKT and p\u2010ERK, reduced retinal reactive oxygen species (ROS) and 4\u2010HNE levels, improved autophagic flux, and mitigated apoptosis. In summary, WIF1 plays a key role in alleviating angiogenesis and in improving visual function in OIR mice by suppressing the Wnt\/\u03b2\u2010catenin\u2010VEGF signaling pathway and ROS levels. WIF1 is an excellent candidate for targeted therapy against RNV associated diseases.<\/jats:p>","DOI":"10.1002\/biof.1824","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T05:01:55Z","timestamp":1643173315000},"page":"683-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Wnt inhibitory 1 ameliorates neovascularization and attenuates photoreceptor injury in an oxygen\u2010induced retinopathy mouse model"],"prefix":"10.1002","volume":"48","author":[{"given":"Wei","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Xiangya Hospital Central South University  Changsha Hunan Province China"},{"name":"Hunan Key Laboratory of Ophthalmology  Changsha Hunan Province China"},{"name":"Department of Ophthalmology, Central Hospital of Xiangtan  Xiangtan Hunan Province China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya 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