Abstract
Purpose: :
To investigate the effect of the absence of ganglion cells on the development of human retinal vasculature.
Methods: :
Anencephaly (AnC) and age-matched control eyes derived from each 3 spontaneously aborted fetus (ranging from 15 to 20 weeks gestation) were subjected to immunofluorescence staining for HIF-1α, Thy-1, glial fibrillary acidic protein (GFAP) & platelet/endothelial cell adhesion molecule (PECAM) and apoptosis assay. In developing mouse retina, Western blotting for hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) was performed. Under hypoxic condition (O2 < 1%), cellular proliferation and VEGF mRNA expression in astrocytes were measured.
Results: :
Apoptotic cells in AnC retina were primarily localized in the ganglion cell layer (GCL), whereas apoptotic cells in normal retina were distributed in the retinoblastic layer. With increase of apoptotic cells in GCL of AnC retina, HIF-1α expression were severely distinguished in avascular retina and GFAP expression in junctional area between avascular and vascular retina was much reduced, accompanied by decrease of PECAM expression compared to normal retina. In developing mouse retina, HIF-1α and VEGF expression were high in hypoxic retina of early stage with incomplete vascular development and then progressively decreased with regression to arborous pattern of matured vascular networks. In hypoxic condition, a significant increase in cellular proliferation and VEGF mRNA expression was observed in astrocytes.
Conclusions: :
Our results suggest that vascular attenuation in AnC retina could be closely related to the absence of ganglion cells as the metabolic demander to induce retinal vascular development.
Keywords: retinal development • ganglion cells • hypoxia