Molecular imaging of metalloproteinases (MMPs) in patients with proliferative diabetic retinopathy (PDR), central serous chorioretinopathy (CSC) and branch retinal vein occlusion (BRVO)

Abstract

Abstract: : Purpose: MMPs have been implicated in a variety of diseases. Recently, in PDR, MMP–2 and MMP–9 have been implicated in the formation of fibrovascular tissues. Using new molecular imaging techniques, our aim was to investigate whether these local effects can be recognized systemically, and whether alterations in the MMP profiles can be correlated with the incidence and progression of PDR. Methods: Gelatinase activity (in relative units) of MMP–2 and MMP–9 in serum of 6 diabetic patients (DP) with moderate PDR, 9 DP with fairly normal retina, and of non–diabetic patients (NDP) with either CSC (n=9) or BRVO (n=5) was determined using gel electropheresis and measuring gelatinase activity A and B by densiometric analysis of zymography at 62 kDa and 82 kDa zones corresponding to the active form of MMP–2 and MMP–9 respectively. In each of these patients, retinal fluorescein angiography was performed to evaluate retinal involvement. Results: The specific activity of MMP–2 und MMP–9 was markedly increased in DP with PDR compared to those without retinopathy. MMP–2 activity was measured at 1.860 on average and MMP–9 at 1.165 versus 0.714 and 0.539, respectively. While the patients with BRVO revealed a MMP–2 activity level of 1.320 on average and 0.633 for MMP–9, patients with CSC showed 0.376 on average for MMP–2 and 0.623 for MMP–9. Conclusion: Differences in serum gelatinase activity, whether primary or secondary, are found between DP with and without PDR and between NDP, especially when comparing PDR and CSC. Comparatively increased MMP–2 activity in patients with BRVO might indicate a possible contribution of this enzyme in the pathogenesis of subsequent vitreoretinal disease. The level of systemic MMP–9 activity, on the other hand, might be a possible marker only for DP with PDR. Systemic alterations therefore might allow the ex vivo monitoring of retinal disease and might become useful in predicting the incidence or progression of PDR. Future studies will aim at a possible time correlation between pattern changes of certain proteins and the onset of diabetic neovascularisation.

Keywords: clinical research methodology • gene/expression • diabetic retinopathy