Izumi Yuasa1, Ning Ma2, Hisashi Matsubara3, Yoshihiro Fukui2, Yukitaka Uji3. 1. Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. i-yama28@clin.medic.mie-u.ac.jp. 2. Department of Anatomy and Developmental Neurobiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima-Shi, Tokushima, Japan. 3. Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Abstract
PURPOSE: To examine the nitrosative and oxidative DNA damage induced by 8-nitroguanine and 8-hydroxy-2-deoxy guanosine (8-OHdG), and to determine the role played by inducible nitric oxide synthase (iNOS) in damage to DNA in the retina of the Goto-Kakizaki (GK) rat. METHODS: Experiments were performed on GK rats, an animal model of spontaneous type 2 diabetes without obesity or visible diabetic vascular lesions. Immunohistochemistry was used to determine the retinal distribution of 8-nitroguanine, 8-OHdG, and iNOS in GK rats and control rats. The change in the expression of 8-nitroguanine and 8-OHdG in GK rats was also determined following an intravitreal injection of 1400W, an inhibitor of iNOS activity. RESULTS: Immunohistochemical analysis showed that 8-nitroguanine and 8-OHdG were expressed strongly in the inner nuclear layer of GK retinas but only weakly in control retinas. This expression was correlated with an increase in the expression of iNOS in GK retinas, which was confirmed by the inhibition of iNOS activity by 1400W. CONCLUSION: These findings demonstrate that iNOS plays a crucial role in nitrosative and oxidative DNA damage in GK rats, suggesting a retinal neurotoxic role of nitric oxide and superoxide in diabetic retinas.
PURPOSE: To examine the nitrosative and oxidative DNA damage induced by 8-nitroguanine and 8-hydroxy-2-deoxy guanosine (8-OHdG), and to determine the role played by inducible nitric oxide synthase (iNOS) in damage to DNA in the retina of the Goto-Kakizaki (GK) rat. METHODS: Experiments were performed on GK rats, an animal model of spontaneous type 2 diabetes without obesity or visible diabetic vascular lesions. Immunohistochemistry was used to determine the retinal distribution of 8-nitroguanine, 8-OHdG, and iNOS in GK rats and control rats. The change in the expression of 8-nitroguanine and 8-OHdG in GK rats was also determined following an intravitreal injection of 1400W, an inhibitor of iNOS activity. RESULTS: Immunohistochemical analysis showed that 8-nitroguanine and 8-OHdG were expressed strongly in the inner nuclear layer of GK retinas but only weakly in control retinas. This expression was correlated with an increase in the expression of iNOS in GK retinas, which was confirmed by the inhibition of iNOS activity by 1400W. CONCLUSION: These findings demonstrate that iNOS plays a crucial role in nitrosative and oxidative DNA damage in GK rats, suggesting a retinal neurotoxic role of nitric oxide and superoxide in diabetic retinas.
Authors: D A Wink; K S Kasprzak; C M Maragos; R K Elespuru; M Misra; T M Dunams; T A Cebula; W H Koch; A W Andrews; J S Allen Journal: Science Date: 1991-11-15 Impact factor: 47.728
Authors: B Cameron Carr; Caitlyn E Emigh; Lea D Bennett; Andrew D Pansick; David G Birch; Chan Nguyen Journal: Retina Date: 2017-01 Impact factor: 4.256