Vascular endothelial growth factor-B and retinal vascular development in the mouse.

Abstract

Vascular endothelial growth factor-A (VEGF-A) is crucial to retinal vascular growth, both normal and pathological. VEGF-B, recently characterized, is reported to be expressed in retinal tissues, but the importance of VEGF-B to retinal vascular development remained unknown. The aim of this study was to analyse retinal vascular growth in the Vegfb-/- knockout mouse. Retinal vascular growth was measured in Vegfb-/- knockout mice raised under normal conditions, and Vegfb-/- knockout mice with an oxygen-induced proliferative retinopathy. Wild type Vegfb+/+ mice served as controls. Vessels were perfused with ink and retinal flatmounts secondarily labelled with FITC-lectin (BS-1, Griffonia simplicifolia). Area and diameter of retinal growth and retinal vascular growth were recorded over days 0-20, and capillary density and mean diameter recorded from day 17 pups. A variety of techniques confirmed that Vegfb+/+ mice expressed VEGF-B and that VEGF-B expression was absent in Vegfb-/- mice. Vegfb-/- mice raised in room air showed no significant differences from Vegfb+/+ controls. No differences were found in oxygen-induced retinopathy between Vegfb-/- and Vegfb+/+ pups in either the extent of the initial oxygen-induced ablation, or in the regrowth of retinal vessels or vitreal (neovascular) sprouts; vitreal sprouts are important markers of the abnormal proliferative response, and are maximally expressed on day 17 in this model of oxygen-induced retinopathy. These results indicate that a lack of VEGF-B does not significantly affect development of the retinal vasculature under normal conditions, nor does it appear to affect the proliferative retinal responses seen in oxygen-induced retinopathy.