An-Jie Du1, Bing Ren, Xiao-Wei Gao, Lei Yang, Yan Fu, Xu-Dong Zhao. 1. Ophthalmic Center, No. 474 Hospital of Chinese PLA, Urumqi 830013, Xinjiang Uygur Autonomous Region, China ; Department of Ophthalmology, Yuncheng Central Hospital, Yuncheng 044000, Shanxi Province, China.
Abstract
AIM: To explore the protective effects of aminoguanidine (AG) on retinal apoptosis in mice with oxygen-induced retinopathy (OIR). METHODS: A total of 80 C57BL/6J mice, aged 7 days, were randomly divided into four groups: normal, high oxygen, high oxygen saline and high oxygen treated with AG. In the normal group, mice were housed in normoxic conditions from postnatal day P7 to P17. Mice in the other 3 groups were placed under hyperoxic conditions (75±2%O2) in an oxygen-regulated chamber for 5 days and subsequently placed in normoxic conditions for 5 days. Mice in the AG group were treated once daily, from P12 to P17, with AG hemisulfate (100mg/kg body weight, intraperitoneally) dissolved in physiological saline. An equivalent amount of 0.9% physiological saline was administered, as above, to mice in the high oxygen saline group. Ten mice were randomly selected from each group on P14 and on P17, euthanized and the retinas examined. Apoptotic cells in the retina were detected using the terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. The expression of nitric oxide synthase (iNOS) in the retina was detected by immunohistochemistry and changes in rod cells were observed using electron microscopy. RESULTS: TUNEL-positive cells and iNOS immunoreactive neurons were present in the inner nuclear and ganglion cell retinal layers of mice in the high oxygen group. The number of TUNEL-positive cells was significantly greater in the high oxygen group compared with the normal group (t=-20.81, P 14d <0.05; t=-15.05, P 17d <0.05). However, the number of TUNEL-positive cells in the AG treatment group was significantly lower (t=-13.21, P 14d<0.05; t=-6.61, P 17d <0.05) compared with the high oxygen group. The expression of iNOS was significantly higher in the high oxygen group compared with the normal group (t=-21.95, P 14d<0.05; t=-17.30, P 17d<0.05). However, the expression of iNOS in the AG treatment group was significantly lower (t=-12.17, P 14d<0.05; t=-10.30, P 17d<0.05) compared with the high oxygen group. The outer segments of the rods were disorganized and short in the high oxygen group. Rod morphology appeared to be slightly improved in the AG group. CONCLUSION: AG may protect retinal neurons in OIR by inhibiting apoptosis. The mechanism may be related to iNOS.
AIM: To explore the protective effects of aminoguanidine (AG) on retinal apoptosis in mice with oxygen-induced retinopathy (OIR). METHODS: A total of 80 C57BL/6J mice, aged 7 days, were randomly divided into four groups: normal, high oxygen, high oxygen saline and high oxygen treated with AG. In the normal group, mice were housed in normoxic conditions from postnatal day P7 to P17. Mice in the other 3 groups were placed under hyperoxic conditions (75±2%O2) in an oxygen-regulated chamber for 5 days and subsequently placed in normoxic conditions for 5 days. Mice in the AG group were treated once daily, from P12 to P17, with AG hemisulfate (100mg/kg body weight, intraperitoneally) dissolved in physiological saline. An equivalent amount of 0.9% physiological saline was administered, as above, to mice in the high oxygen saline group. Ten mice were randomly selected from each group on P14 and on P17, euthanized and the retinas examined. Apoptotic cells in the retina were detected using the terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method. The expression of nitric oxide synthase (iNOS) in the retina was detected by immunohistochemistry and changes in rod cells were observed using electron microscopy. RESULTS: TUNEL-positive cells and iNOS immunoreactive neurons were present in the inner nuclear and ganglion cell retinal layers of mice in the high oxygen group. The number of TUNEL-positive cells was significantly greater in the high oxygen group compared with the normal group (t=-20.81, P 14d <0.05; t=-15.05, P 17d <0.05). However, the number of TUNEL-positive cells in the AG treatment group was significantly lower (t=-13.21, P 14d<0.05; t=-6.61, P 17d <0.05) compared with the high oxygen group. The expression of iNOS was significantly higher in the high oxygen group compared with the normal group (t=-21.95, P 14d<0.05; t=-17.30, P 17d<0.05). However, the expression of iNOS in the AG treatment group was significantly lower (t=-12.17, P 14d<0.05; t=-10.30, P 17d<0.05) compared with the high oxygen group. The outer segments of the rods were disorganized and short in the high oxygen group. Rod morphology appeared to be slightly improved in the AG group. CONCLUSION: AG may protect retinal neurons in OIR by inhibiting apoptosis. The mechanism may be related to iNOS.
Entities:
Keywords:
aminoguanidine; apoptosis; inhibitor of nitric oxide synthase; retinopathy of prematurity
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