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The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy
Author(s) -
Kim Clifford,
Smith Kaylee E.,
Castillejos Alexandra,
DiazAguilar Daniel,
SaintGeniez Magali,
Connor Kip M.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-280834
Subject(s) - retinal , complement system , cd59 , alternative complement pathway , laser capture microdissection , neovascularization , vascular endothelial growth factor , biology , vascular endothelial growth factor a , blood vessel , endocrinology , medicine , immune system , angiogenesis , immunology , andrology , vegf receptors , gene expression , biochemistry , gene
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.—Kim, C., Smith, K. E., Castillejos, A., Diaz‐Aguilar, D., Saint‐Geniez, M., Connor, K. M., The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy. FASEB J. 30, 1300–1305 (2016). www.fasebj.org