AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2010;2(2):181-189

Original Article
Attenuation of diabetic retinopathy by enhanced inhibition of MMP-2
and MMP-9 using aspirin and minocycline in streptozotocin-diabetic

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).

Key words: Matrix metalloproteinase 2, matrix metalloproteinase 9, extracellular matrix, diabetic retinopathy

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Address all correspondence to:
Veeranjaneyulu Addepalli, PhD
Department of Pharmacology,
School of Pharmacy and Technology Management,
NMIMS University, Vile Parle (W),
Mumbai, 400 056
Ph No: +91 22 64521148
Fax No: +91 22 26185422