Purpose: The neovascularization is a common complication of proliferative diabetic retinopathy (PDR). Previously, we have demonstrated an increased expression of LRP-1/a2M system in patients with neovascular eye disease suggesting that it is involved in modulating the extracellular proteinase activity. However, it has been reported that a2M is proteolytically degraded in inflammatory disease altering its function as proteinase inhibitor. Hence, in this work we evaluate the proteolytic state of a2M 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 programed for vitrectomy surgery. We dived 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 a2M 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,
Results: An enhanced proteolytic fragmentation of a2M 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.
Conclusion: These results suggest that the neovascularization of PDR occur with a decreased function of a2M and enhanced MMP activities, which can partially be reverted after laser treatment. Thus, the structural a2M state could be used as a course control of post laser treatment PDR.
