INCREASED EXPRESSION OF PLACENTA GROWTH-FACTOR IN PROLIFERATIVE DIABETIC-RETINOPATHY

Proliferative diabetic retinopathy is thought to be mediated by the hy poxic regulation of angiogenic growth factors, in particular the vascu lar endothelial growth factor (VEGF) family. The aim of this study was to determine if placental growth factor (PIGF), a recently identified member of the VEGF family, was expressed in diabetic eyes undergoing preretinal neovascularization. Rabbit anti-PIGF antiserum was raised u sing a 20-amino acid N-terminal sequence to PIGF and did not cross rea ct with VEGF(165). Immunohistochemistry was performed on specimens of normal retina (n = 8), diabetic retina in the absence (n = 7) and pres ence (n = 4) of proliferative retinopathy, scatter laser-treated diabe tic retina (n = 7), excised fibrovascular preretinal membranes (n = 12 ), and nondiabetic fibrocellular epiretinal (n = 7) membranes. PIGF le vels were also determined in vitrectomy specimens from patients with e ither proliferative diabetic retinopathy or macular hole. PIGF immunor eactivity was intensely localized to the endothelial and perivascular regions of newly formed blood vessels of excised fibrovascular prereti nal membranes. Intense localization of PIGF protein was also observed in superficial retinal vessels in diabetic retinae adjacent to neovasc ular preretinal membranes. Localization of PIGF was weak or absent in diabetic retinae that showed no evidence of neovascular proliferation. PIGF protein was also absent in normal retinae, in diabetic retinae t hat had received extensive treatment with scatter laser photocoagulati on, and in nonvascularized epiretinal membranes. PIGF was present in a ll diabetic vitreous samples (mean 103 pg/ml) but nondetectable in con trol samples. These results strongly implicate a role for PIGF in the pathogenesis of proliferative diabetic retinopathy.