VEGF ₁₆₅b in the developing vasculatures of the fetal human eye

VEGF ₁₆₅b is an anti-angiogenic form of VEGF ₁₆₅ produced by alternative splicing. The localization of pro-angiogenic VEGF ₁₆₅ and anti-angiogenic VEGF ₁₆₅b was investigated during development of the vasculatures in fetal human eyes from 7 to 21 weeks gestation (WG). The fetal vasculature of vitreous, which includes tunica vasculosa lentis (TVL), had moderate VEGF ₁₆₅ immunoreactivity at 7WG and very little VEGF ₁₆₅b. Both forms were elevated at 12WG. VEGF ₁₆₅ then decreased around 17WG when the TVL regresses but VEGF ₁₆₅b remained elevated. In choroid, VEGF ₁₆₅ was present in forming choriocapillaris (CC) and retinal pigment epithelium (RPE) at 7WG while VEGF165b was present in CC and mesenchymal precursors within the choroidal stroma. By 21WG, both forms were elevated in RPE and choroidal blood vessels but VEGF ₁₆₅b was apical and VEGF ₁₆₅ basal in RPE. Diffuse VEGF ₁₆₅ immunoreactivity was prominent in 12WG innermost retina where blood vessels will form while VEGF ₁₆₅b was present in most CXCR4 ⁺ progenitors in the inner neuroblastic layer and migrating angioblasts in the putative nerve fiber layer. By 21WG, VEGF ₁₆₅ was present in nerve fibers and VEGF ₁₆₅b in the inner Muller cell process. The localization of VEGF ₁₆₅b was distinctly different from VEGF ₁₆₅ both spatially and temporally and it was often associated with nucleus in progenitors.