Original Article Attenuation of diabetic retinopathy by enhanced inhibition of MMP-2 and MMP-9 using aspirin and minocycline in streptozotocin-diabetic rats
Lokesh Kumar Bhatt, Veeranjaneyulu Addepalli
Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, 400 056, India
Received January 20, 2010; accepted February 8, 2010, available online February 12, 2010
Abstract: Interruptions of Matrix Metalloproteinase-2 (MMP-2) and Matrix Metalloproteinase-9 (MMP-9) have been shown to reduce the ensuing threatening risk factors of vascular complications of diabetes by alteration in Extracellular Matrix (ECM).We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin, a non-selective COX and tPA inhibitor and this combination can reduce progression of diabetic retinopathy. Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Four weeks after diabetes induction rats were treated with minocycline (50 mg/kg, p.o.) per se, aspirin (50 mg/kg, p.o.) per se, or minocycline in combination with aspirin for a period of four weeks. At the end of eighth week rats were anesthetized and electroretinograms were recorded. B-wave latency, B-wave amplitude and retinal permeability were measured. Histology was done and retinal thickness was measured. Zymography was carried out for MMP-2 and MMP-9 level determinations. B-wave amplitude was significantly decreased while B- wave latency was significantly increased in diabetic group when compared with normo-glycemic rats. Treatment with combination of minocycline and aspirin significantly reversed B-wave amplitude and latency compared with vehicle-treated diabetic controls. Blood retinal permeability and retinal thickness were also significantly attenuated by the treatment of minocycline in combination with aspirin. Results of the present study suggest that MMP-2 and MMP-9 inhibition in presence of COX inhibitor prevents the development of experimental diabetic retinopathy in rats and can be a potential approach for the treatment.(AJTR201001004).
Address all correspondence to: Veeranjaneyulu Addepalli, PhD Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, 400 056 India. Ph No: +91 22 64521148 Fax No: +91 22 26185422 E-mail: firstname.lastname@example.org