Flk-1, a receptor for vascular endothelial growth factor, is expressed in the neural cells of developmental human retinas

Abstract

Membrane receptor tyrosine kinase Flk-1 (also designated VEGF-R2) is a high-affinity receptor for vascular endothelial growth factor (VEGF) and putatively involved in the growth of the vascualr endothelial cells. However, recently some researchers found that Flk-1 expresses in retinal progenitor cells of developmental mouse retinas and a role of VEGF for neural retinal development is implied. In the present study, we investigated the expression of Flk-1 and VEGF in the developmental human retinas ranging from 10.5 weeks of gestation (WG) to 22 WG by immunohistochemistry. We found that as early as 10.5 WG, Flk-1-immunoreactivity (IR) expresses in cell membrane of retinal progenitor cells of the inner retinas. At 17 WG, Flk-1-IR is expressed strongly in many cells of the ganglion cell layer and weakly in some cells at the innermost of inner nuclear layer. After 21 WG, Flk-1-IR is still expressed in cells of ganglion cell layer and most strongly in cells at innermost of inner nuclear layer and in addition, in horizontal cells. Flk-1-IR also expresses in choroid vessels outside the retinas at all stages, and in the retinal vessels after 18 WG. Meanwhile, VEGF-IR occurs in the Muller cells through all these time periods. In conclusion, we have shown the expression of Flk-1 in retinal progenitor cells and later on in neural retinal cells before retinal vessels occur in the retinas. Together with the consistent expression of VEGF in this developmental period, this study suggests that VEGF plays a nonvascular role for the development of human retinas. Supported by The University of Hong Kong, Research Grant Council of Hong Kong and Croucher Foundation