Purchase this article with an account.
Y. Yoshida, S.-I. Yamagishi, T. Imaizumi, M. Arai, R. Yamakawa; Minodronate, a Newly Developed Nitorgen-Containing Bisphosphonate, Prevents the Development of Experimental Diabetic Retinopathy via Anti-Oxidative Properties. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4967.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have recently demonstrated that minodronate, a newly developed nitrogen-containing bisphosphonate, inhibits tumor-associated angiogenesis by suppressing vascular endothelial growth factor-signaling via inhibition of NADPH oxidase activity. In this study, we investigated whether minodronate could prevent the development of experimental diabetic retinopathy through its anti-oxidative properties.
Streptozotocin-induced diabetic rats were treated with or without intraperitoneal injection of minodronate (400µg/kg/day) for 6 weeks. Early neuronal derangements in the retina were evaluated by electroretinogram (ERG). ERG was recorded by the contact lens electrode containing light emitted diode (LED) for stimulus. The oscillatory potentials (OPs) were determined as sum of each waves. Retinal levels of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, and apoptosis were quantified by means of immunohistochemistry. NADPH oxidase activity in the retina was measured with lucigenin luminescence.
The amplitude of a-wave and OPs in diabetic rats showed a significant decrease; 75% and 50% respectively compared with those of controls (p< 0.01). The latency of OPs in diabetic rats were prolonged 24 % more than that of controls (p< 0.01). The levels of 8-OHdG and apoptosis were increased in the outer nuclear layer of diabetic retinas. NADPH oxidase activity in the diabetic retina was also increased by about 2.5-fold compared with that in control. Minodronate treatment significantly decreased the levels of 8-OHdG and apoptosis compared with that in diabetic rats (p< 0.01). NADPH oxidase activity was also decreased by 46% compared with that in diabetic rats and ERG alterations were similar to control rats with minodronate.
Minodronate treatment was found to significantly inhibit retinal cell apoptosis and neuronal dysfunction in experimental diabetic retinopathy by suppressing NADPH oxidase-mediated oxidative stress generation. Minodronate may have a therapeutic potential in the treatment of early diabetic retinopathy.
This PDF is available to Subscribers Only