title: The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy.
abstract: Proliferative retinopathic diseases often progress in 2 phases: initial regression of retinal vasculature (phase 1) followed by subsequent neovascularization (NV) (phase 2). The immune system has been shown to aid in vascular pruning in such retinopathies; however, little is known about the role of the alternative complement pathway in the initial vascular regression phase. Using a mouse model of oxygen-induced retinopathy (OIR), we observed that alternative complement pathway-deficient mice (Fb(-/-)) exhibited a mild decrease in vascular loss at postnatal day (P)8 compared with age- and strain-matched controls (P = 0.035). Laser capture microdissection was used to isolate the retinal blood vessels. Expression of the complement inhibitors Cd55 and Cd59 was significantly decreased in blood vessels isolated from hyperoxic retinas compared with those from normoxic control mice. Vegf expression was measured at P8 and found to be significantly lower in OIR mice than in normoxic control mice (P = 0.0048). Further examination of specific Vegf isoform expression revealed a significant decrease in Vegf120 (P = 0.00032) and Vegf188 (P = 0.0092). In conjunction with the major modulating effects of Vegf during early retinal vascular development, our data suggest a modest involvement of the alternative complement pathway in targeting vessels for regression in the initial vaso-obliteration stage of OIR.
authors.affiliation: *Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and Schepens Eye Research Institute, Boston, Massachusetts, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Kim
authors.affiliation: *Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and Schepens Eye Research Institute, Boston, Massachusetts, USA.
authors.forename: Kaylee E
authors.initials: KE
authors.lastname: Smith
authors.affiliation: *Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and Schepens Eye Research Institute, Boston, Massachusetts, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Castillejos
authors.affiliation: *Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and Schepens Eye Research Institute, Boston, Massachusetts, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Diaz-Aguilar
authors.affiliation: *Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and Schepens Eye Research Institute, Boston, Massachusetts, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Saint-Geniez
authors.affiliation: *Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and Schepens Eye Research Institute, Boston, Massachusetts, USA kip_connor@meei.harvard.edu.
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000276:immunology*; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012160:Retina / Q000276:immunology* / Q000378:metabolism; D015861:Retinal Neovascularization / Q000276:immunology* / Q000378:metabolism; D012171:Retinal Vessels / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000276:immunology* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen
keywords: Cd55; Cd59; OIR; Vegf; factor b; innate immune system