The effect of nitrogen monoxide and its synthase on the diabetic retinal damage

Objective To further investigate the effect of NO and its synthase on the retinal oxidative damages in diabetes. Methods Diabetic rat model was induced by injection with streptozotoc. Saline was injected in the controls. The retina was excised and studied 2 w and 20 w after the establishment of the experimental model and the controls. The distribution and content of 3-nitrotyrosine (3-NT) in the retina were analyzed by employing immunohistochemical method and icon manipulation technique. The proteins and mRNA expression of inducible nitric oxide synthetase (iNOS) and neuronal nitric oxide synthetase (nNOS) were determined by employing immunohistochemical method and RT-PCR technique. Results The 3-NT expression in the retina of diabetic rats increased in the second week of diabetes. The positive cells only distributed in the ganglion cell layer, indicating that the retinal damage of diabetic rats first appeared in the ganglion cell layer. The NT expression increased significantly in the 20 week of diabetes and the positive cells distributed in the whole layers of retina, indicating that the retinal oxidative damages was in progress step by step and the production of NO increased with the progress of diabetes. Compared with the control, the iNOS expression increased and nNOS decreased in the 2 w of diabetes. The former increased further while the latter nearly disappeared in the 20 w, indicating that the increasing production of NO in the retina of diabetic rats was related with the decrease of nNOS expression and the increase of iNOS expression.Conclusion The diabetic retinal damages first appear in the ganglion cell layer. Later on, the function of the external retinal layers is impaired. The retinal damages at the early stage of diabetes mainly focus on the ganglion cell layer. In the diabetic rat models, the retinal damages are closely related with the increase of NO which results from the decrease of nNOS expression and increase of iNOS expression.