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

Abstract

VEGF165b is an anti-angiogenic form of VEGF165 produced by alternative splicing. The localization of pro-angiogenic VEGF165 and anti-angiogenic VEGF165b 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 VEGF165 immunoreactivity at 7WG and very little VEGF165b. Both forms were elevated at 12WG. VEGF165 then decreased around 17WG when the TVL regresses but VEGF165b remained elevated. In choroid, VEGF165 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 VEGF165b was apical and VEGF165 basal in RPE. Diffuse VEGF165 immunoreactivity was prominent in 12WG innermost retina where blood vessels will form while VEGF165b was present in most CXCR4+ progenitors in the inner neuroblastic layer and migrating angioblasts in the putative nerve fiber layer. By 21WG, VEGF165 was present in nerve fibers and VEGF165b in inner Muller cell process. The localization of VEGF165b was distinctly different from VEGF165 both spatially and temporally and it was often associated with nucleus in progenitors.

Co-expression of endothelial and neuronal nitric oxide synthases in the developing vasculatures of the human fetal eye

“…VEGF promotes NO production and also induces eNOS and iNOS expression in vascular endothelial cells in vitro [20]. We have recently observed the anti-angiogenic VEGF 165 b in the nucleus of the vascular progenitors that have nNOS in their nuclei and the angiogenic splice variant VEGF 165 was in the cytoplasm of the same cells [21]. Furthermore, inhibition of in vivo NO production results in reduced angiogenesis and vascular permeability induced by VEGF.…”

From Blood Islands to Blood Vessels: Morphologic Observations and Expression of Key Molecules during Hyaloid Vascular System Development

“…Our previous study demonstrated the anti-angiogenic form of VEGF 165 b was not detectable in BI of vitreous but the angiogenic VEGF 165 was present. 52 NG-2 immunoreactivity, a marker for pericytes, was observed in early BI cells, and some of these cells coexpressed the endothelial marker CD31. Moreover, in our TEM analysis, it was impossible to distinguish endothelial cells or pericytes in these formations based on their ultrastructural characteristics.…”

“…Cells in these structures were primitive erythroblasts and angioblasts that formed aggregates and expressed hematopoietic stem cell markers, VEGFR2, c-Kit, and CXCR4. The ligands for these molecules, VEGF165, 52 SCF, and SDF-1, 34 are present at high levels in lens and inner retina as well as diffusely in the vitreous during BI formation; therefore, these ligands probably function in the homing of these cells into the vitreous space near lens and retina. Some cells in BI coexpressed embryonic hemoglobin and endothelial cell markers reflecting a dual hematoendothelial phonotype.…”

Relative expression of vascular endothelial growth factor isoforms in squamous cell carcinoma of the head and neck

“…The mRNA encoding VEGF inhibitory isoforms has been identified in renal cortical tissue and several other physiological human tissues through a variety of experimental techniques, whereas downregulation has been observed in a variety of angiogenic conditions, cancer included, substantiating their antiangiogenic role . Interestingly, however, 1 research group has recently questioned the interpretation of VEGF isoform expression patterns, predicated on an inability to detect inhibitory isoform expression using an reverse transcriptase‐polymerase chain reaction‐based approach with isoform‐common primers, and the unexpected detection of putative VEGF xxx b species in cell lines that preclude VEGF xxx b alternative splicing .…”