VHL gene deletion and enhanced VEGF gene expression detected in the stromal cells of retinal angioma

Objectives: Retinal angioma frequently occurs in von Hippel-Lindau (VHL) di sease. However, VHL gene alterations have not been documented in retinal an giomas. Methods: Using tissue microdissection and polymerase chain reaction amplifi cation, we have analyzed 7 retinal angiomas associated with VHL disease for loss of heterozygosity of the VHL gene. Tn addition, vascular endothelial growth factor expression was evaluated in these tumors by immunohistochemis try and in situ hybridization. Results: All 6 informative retinal angiomas showed loss of heterozygosity o f the VHL gene. Loss of heterozygosity was detected in vacuolated "stromal" cells, but not in vascular cells or reactive glial tissue. Vascular endoth elial growth factor protein and messenger RNA were also present in vacuolat ed "stromal" cells. Conclusions: These findings suggest that vacuolated "stromal" cells represe nt the true neoplastic component in retinal angioma. These cells express va scular endothelial growth factor and therefore may be responsible for abund ant neovascularization of retinal angioma.