Abstract
Abstract: :
Purpose: Bactericidal/Permeability–Increasing Protein (BPI), a 55–kDa cationic protein initially found in the azurophilic granules of neutrophils, has been shown to have anti–angiogenic properties. We evaluated the presence and concentration of BPI in the vitreous and the plasma of patients with various levels of diabetic retinopathy to determine the role of BPI in this disorder. Methods: Undiluted vitreous (28 patients) and plasma (40 patients) were collected and frozen at –80oC until assayed. BPI was measured using a capture ELISA with 0.055+0.062 ng/ml detection limit. Retinopathy level was determined according to the ETDRS clinical classification system. Bovine retina and primary cultures of bovine retinal pericytes (BRPC), endothelial cells (BREC), and pigment epithelial cells (BRPE) were analyzed for BPI expression using RT–PCR. Results: BPI was detected more frequently in vitreous of patients with quiescent proliferative diabetic retinopathy (33%, QPDR) than in those with active PDR (12.5%), nonproliferative DR (0%, NPDR) or nondiabetic patients (0%, NDM). In eyes with detectable BPI, concentrations were 3.4 fold higher in patients with QPDR than PDR (0.525 ng/ml+0.09 vs 0.155 ng/ml+0.017, p=0.094) and higher than in NPDR (p=0.012) or NDM (p=0.001). BPI was detectable in the serum of most patients (75%, 73%, 63% & 66% for QPDR, PDR, NPDR and NDM, respectively) without statistically significant differences between groups. Serum concentrations also were not statistically different, ranging from 0.520+0.134 to 0.566+0.117 ng/ml. BPI mRNA expression was detected in bovine retina and primary cultures of BRPE, BRPC and BREC cells. BPI was most prominently expressed in BRPE. Conclusions: These data are the first to demonstrate BPI in the vitreous, retina and cultured retinal cells, suggesting a previously unappreciated retinal origin of BPI. Vitreous concentrations of BPI appear independent of plasma concentration and increased vitreous BPI may be associated with quiescence of proliferative diabetic retinopathy.
Keywords: diabetic retinopathy • retinal neovascularization • cytokines/chemokines