IMPACT OF ALTERED EXPRESSION OF MATRIX METALLOPROTEINASES (MMPs) ON THE DEVELOPMENT AND SEVERITY OF DIABETIC RETINOPATHY
Journal Title: Journal of Evolution of Medical and Dental Sciences - Year 2013, Vol 2, Issue 21
Abstract
The primary cause of visual loss in the country like India are cataract, glaucoma, malnutrition, age related macular degeneration and diabetic retinopathy (DR)1.DR is the most common microvascular complication of both type 1 and type 2 diabetes mellitus (DM) and is the most frequent single cause of newly reported cases of blindness among the adults in the age group of 20 – 75 years 2. Visual loss due to diabetes either develops from increased permeability of retinal vessels (diabetic macular edema) or by proliferation of new retinal vessels 2. Several angiogenic factors such as VEGF, PDGF, and TNF–α exhibit their potential signature on the development and progression of DR which ultimately results in the neovascularization process3. So far only VEGF has been largely implicated in deposition of extracellular matrix (an essential step in the new vessel formation) and play the crucial role by stimulating angiogenesis and inhibiting the endothelial function in retinal ischemic conditions.3 Among the various processes that regulate angiogenesis, the generation of proteolytic activity is thought to be pivotal in the regulation of cell migration and capillary tube formation. Pericellular proteolysis and capillary-like tubule formation by endothelial cells are achieved by cell-bound urokinase-type plasminogen activator (u-PA) and plasmin as well as matrix metalloproteinases (MMPs) 4. Membrane-type MMPs (MT - MMPs) have been suggested to play a key role in angiogenesis, in addition to the gelatinases MMP-2 and -9 5. As a family of zinc-binding, calcium-dependent endopeptidases, matrix metalloproteinases (MMPs) expressed in various tissues and cells are responsible for the dissolution of extracellular matrix 6.MMPs play a major role in normal development, reproduction, and tissue remodeling7. In addition, these molecules are involved in a number of pathogenic processes including cancer, arthritis and other angiogenic disorder.8 Recently there have been a number of important discoveries on the role of MMPs in the eye. MMP activity is modulated through interaction with the MMP inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMPs).7 MMP activities are regulated by transcriptional control, by proenzyme activation. MMPs are involved in the degradation of a variety of extracellular matrix (ECM) molecules, and ECM homeostasis. Considering the finding that DR is initially caused by breakdown of inner blood-retinal barrier and later by fibrovascular proliferation; it is possible that MMP expression might change in the development and progression of DR and the extracellular matrix degradation would be also accompanied accordingly. To understand the pathogenic mechanism of the multifactorial disease like DR, we investigate the role of gelatinized MMPs from clinical isolates
Authors and Affiliations
Lakshmi Mandal, Subhojit Choudhuri, Suman Paine, Aditi Sen, Gautam Bhaduri, Basudev Bhattacharya
Keywords
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- EP ID EP158980
- DOI 10.14260/jemds/750
- Views 83
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