Proteolytic State of 2M and MMP Activities in Treated and Non Treated Patients With Proliferative Diabetic Retinopathy

Abstract

Abstract: : Purpose: The neovascularization is a common complication of proliferative diabetic retinopathy (PDR). Previously, we have demonstrated an increased expression of LRP–1/α₂M system in patients with neovascular eye disease suggesting that it is involved in modulating the extracellular proteinase activity. However, it has been reported that α₂M is proteolytically degraded in inflammatory disease altering its function as proteinase inhibitor. Hence, in this work we evaluate the proteolytic state of α₂M as well as MMP–2 and MMP–9 activities in human vitreous, isolated from patients with PDR pre and post laser treatment.Methods: We study vitreous samples from patients with PDR and programmed for vitrectomy surgery. We separated them into two groups: Pacients with previous panphotocoagulation (PP) two weeks before surgery and patients with PDR without PP. Pacients with macular hole or lensectomy were used as control. The proteolytic fragmentation of α₂M was analyzed by western blotting. Vitreous MMP activities were measured by gelatin zymography and gelatinolytic bands were quantified by densitometric, using digital image analysis (Scion Corporation, USA). Results: An enhanced proteolytic fragmentation of α₂M was mostly detected in PDR patients, compared to post laser treatment–PDR patients. The pro MMP–2 activity was similar between non diabetic, PDR and post laser treatment patients, whereas MMP–9 activity was significantly increased in PDR patients, correlating with the disease progression.Conclusions: These results suggest that the neovascularization of PDR occur with a decreased function of α₂M and enhanced MMP activities, which can partially be reverted after laser treatment. Thus, the structural α₂M state could be used as a course control of post laser treatment PDR.

Keywords: diabetic retinopathy • diabetes • ischemia