Attenuation of retinal vascular development and neovascularization in PECAM-1-deficient mice

• Published in: Developmental biology 2008-03, Vol.315 (1), p.72-88
• Main Authors: DiMaio, Terri A., Wang, Shoujian, Huang, Qiong, Scheef, Elizabeth A., Sorenson, Christine M., Sheibani, Nader
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Apoptosis; CD31; Cell Proliferation; Collagen Type IV - metabolism; Endothelial Cells - metabolism; Hyaloid vasculature; Hypoxia - metabolism; Immunohistochemistry; In Situ Nick-End Labeling; Ischemia - physiopathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Nitric Oxide Synthase Type III - metabolism; Oxygen - toxicity; Pericytes - metabolism; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Receptor, EphB2 - genetics; Receptor, EphB2 - metabolism; Receptor, EphB4 - genetics; Receptor, EphB4 - metabolism; Retinal Diseases - pathology; Retinal endothelial cells; Retinal vascularization; Retinal Vessels - growth & development; Retinal Vessels - pathology; Retinopathy of prematurity; Trypsin - pharmacology; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2007.12.008

Platelet–endothelial cell adhesion molecule-1 (PECAM-1/CD31) is expressed on the surface of endothelial cells (EC) at high levels with important roles in angiogenesis and inflammation. However, the physiological role PECAM-1 plays during vascular development and angiogenesis remains largely unknown. Here we determined the role of PECAM-1 in the postnatal development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR) using PECAM-1-deficient (PECAM-1−/−) mice. A significant decrease in retinal vascular density was observed in PECAM-1−/− mice compared with PECAM-1+/+ mice. This was attributed to a decreased number of EC in the retinas of PECAM-1−/− mice. An increase in the rate of apoptosis was observed in retinal vessels of PECAM-1−/− mice, which was compensated, in part, by an increase in the rate of proliferation. However, the development and regression of hyaloid vasculature were not affected in the absence of PECAM-1. We did not observe a significant defect in astrocytes, the number of endothelial tip cell filopodias, and the rate of developing retinal vasculature progression in PECAM-1−/− mice. However, we observed aberrant organization of arterioles and venules, decreased secondary branching, and dilated vessels in retinal vasculature of PECAM-1−/− mice. In addition, retinal neovascularization was attenuated in PECAM-1−/− mice during OIR despite an expression of VEGF similar to that of PECAM-1+/+ mice. Mechanistically, these changes were associated with an increase in EphB4 and ephrin B2, and a decrease in eNOS, expression in retinal vasculature of PECAM-1−/− mice. These results suggest that PECAM-1 expression and its potential interactions with EphB4/ephrin B2 and eNOS are important for survival, migration, and functional organization of EC during retinal vascular development and angiogenesis.