Elevated neprilysin activity in vitreous of patients withproliferative diabetic retinopathy

[摘要] Purpose: Diabetic retinopathy (DR) is the leading cause of blindnessin the industrialized world. Hyperglycemia induces retinal hypoxia,which upregulates a range of vasoactive factors that may lead to macularedema and/or angiogenesis, and hence potentially to sight-threateningretinopathy. The control of signal-peptide activity by cell-surfaceproteases is one of the main factors regulating the development andbehavior of organisms. In mammals, neprilysin is known to play a keyrole in these processes, and its inactivation can initiate cellulardisorganization. Neprilysin is a rate-limiting peptidase involved in thephysiological degradation of amyloid β (Aβ) in the brain. Inthis study, we measured both the enzymatic activity of neprilysin andthe concentration of Aβ in patients with proliferative DR (ascompared to their levels in patients with macular hole), and we analyzedtheir association.Methods: In vitreous samples collected from patients who underwentvitrectomy, an HPLC-fluorometric system (recently established by us),and sensitive and specific enzyme-linked immunosorbent assays were usedto determine the enzymatic activity of neprilysin and the concentrationof Aβ.Results: By comparison with the levels in the control (macular-hole)patients, there was a significant increase in neprilysin activity leveland a significant decrease in Aβ level in proliferative DRpatients. There was a significant inverse correlation between neprilysinand Aβ among all subjects.Conclusions: Neprilysin activity and Aβ concentrationsdisplayed converse changes in patients with proliferative DR.

[学科分类] 生物化学/生物物理