ELEVATED OCULAR LEVELS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN PATIENTS WITH VON-HIPPEL-LINDAU-DISEASE

Background: Von Hippel-Lindau disease (VHL) is a rare autosomal domina nt inherited disorder characterized by highly vascularized rumors in v arious organs. The abundant presence of endothelial cells in VHL tumor s strongly suggest a role of the VHL tumor suppressor gene in the regu lation of angiogenesis. Recently, in vitro studies have shown that the VHL tumor suppressor gene regulates the expression of vascular endoth elial growth factor (VEGF). We investigated whether VHL patiens have i ncreased levels of VEGF in their body fluids. Patients and methods: Th e concentration of VEGF was measured in fluid of the anterior chamber of the eye, serum, urine, and fluid from renal cysts of VHL patients a nd unaffected individuals by ELISA. In addition, levels of basic fibro blast growth factor (bFGF), interleukin-8 (IL-8) and endothelin-l (ET- l) were measured in urine and serum of VHL patients and control subjec ts. Results: In 80% of the VHL patients VEGF was detectable in aqueous fluid of the anterior chamber of their eyes. A strong positive correl ation (r = 0.90) was found between the age of VHL patients and ocular VEGF concentrations. At comparable age, VEGF levels in ocular fluid of VHL patients were significantly higher (P < 0.001) than in unaffected subjects. No correlation was found between VEGF concentration and the presence of retinal angiomas. A 10 and 16 fold increase of VEGF conce ntration was seen in fluid from two independent VHL-related cysts as c ompared with VEGF serum levels of the same patient. The mean concentra tion of VEGF in serum of VHL patients (it = 15) (319 +/- 84 pg/ml) was higher than in matched controls (238 +/- 68 pg/ml; P = NS). The mean concentration of VEGF in urine of VHL patients (128 +/- 36 pg/ml) was lower than in matched controls (183 +/- 25 pg/ml; P = NS). Concentrati ons of VEGF did not correlate with the presence of VHL-related tumors. No differences were observed between concentrations of bFGF, IL-8 and ET-1 in serum and urine of VHL patients and matched controls. Conclus ions: These findings support a role for the VHL tumor suppressor gene in the in vivo regulation of VEGF.