Objective To investigate the protective effect of lipoic acid-niacin(N2L)on blue light-induced retinal in-jury in mice by regulating the nuclear factor-E2-related factor 2(Nrf2)signaling pathway.Methods Forty-eight male C57BL/6 mice were selected and randomly divided into a wild-type group(+)and an Nrf2 knockout group(-).Each group was further randomly subdivided into four parallel subgroups,with six mice in each.These subgroups were designat-ed as Con+,BL+,N2L+,NS+,Con-,BL-,N2L-,and NS-for corresponding treatments.Electroretinography(ERG)was performed to assess retinal function.TUNEL staining was used to detect photoreceptor cell apoptosis in the mouse retinal tissue.Western blot analysis was conducted to measure the expression levels of heme oxygenase-1(HO-1),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X proteins(Bax)in the mouse retinal tissue.Results Compared with those in the Con+group,the amplitudes of the ERG b-wave and the second peak(OS2)of mouse oscillatory potentials(OPs)in BL+,NS+,BL-,N2L-,and NS-groups were decreased significantly under medium-and high-intensity stim-ulating light(all P＜0.05).The cell apoptosis rate and the expression level of Bax proteins in BL+,NS+,BL-,N2L-,and NS-groups were significantly higher than those in the Con+group(all P＜0.05).Compared with those in the BL+group,the amplitudes of the ERG b-wave and OS2 of OPs were increased significantly under medium-and high-intensity stimulating light in N2L+and Con-groups(all P＜0.05).N2L+and Con-groups had a significantly lower cell apopto-sis rate than the BL+group(P＜0.05).BL-and NS-groups had a significantly higher cell apoptosis rate and significant-ly lower Bax levels than the BL+group(all P＜0.05).Compared with those in the N2L+group,the amplitudes of the ERG b-wave and OS2 of OPs were reduced significantly under medium-and high-intensity stimulating light in NS+,BL-,N2L-,and NS-groups(all P＜0.05).The cell apoptosis rate and Bax levels in NS+,BL-,N2L-,and NS-groups were significantly higher than those in the N2L+group(all P＜0.05).The Bax level in the Con-group was significantly lower than that in the N2L+group(P＜0.05).Compared with those in the NS+group,the amplitudes of the ERG b-wave and OS2 of OPs were increased significantly under medium-and high-intensity stimulating light in the Con-group(all P＜0.05).The cell apoptosis rate and Bax levels in the Con-group were significantly lower than those in the NS+group(P＜0.05).Compared with those in the Con-group,the amplitudes of the ERG b-wave and OS2 of OPs were decreased significantly under medium-and high-intensity stimulating light in BL-,N2L-,and NS-groups(all P＜0.05).BL-,N2L-,and NS-groups had a significantly higher cell apoptosis rate and Bax levels than the Con-group(all P＜0.05).HO-1 and Bcl-2 levels in BL+,N2L+,and NS+groups were significantly higher than those in the Con+group(all P＜0.05).Compared with those in the BL+group,HO-1 and Bcl-2 levels were increased significantly in the N2L+group and decreased significantly in Con-,BL-,N2L-,and NS-groups(all P＜0.05).HO-1 and Bcl-2 levels in NS+,Con-,BL-,N2L-,and NS-groups were significantly lower than those in the N2L+group(all P＜0.05).Con-,BL-,N2L-,and NS-groups showed significantly lower HO-1 and Bcl-2 levels than the NS+group(all P＜0.05).The N2L-group had significantly higher HO-1 and Bcl-2 levels than the Con-group(both P＜0.05).Conclusion N2L may antag-onize blue light-induced retinal damage in mice by activating the Nrf2 signaling pathway.

Objective To investigate the protective effect of lipoic acid-niacin(N2L)on blue light-induced retinal in-jury in mice by regulating the nuclear factor-E2-related factor 2(Nrf2)signaling pathway.Methods Forty-eight male C57BL/6 mice were selected and randomly divided into a wild-type group(+)and an Nrf2 knockout group(-).Each group was further randomly subdivided into four parallel subgroups,with six mice in each.These subgroups were designat-ed as Con+,BL+,N2L+,NS+,Con-,BL-,N2L-,and NS-for corresponding treatments.Electroretinography(ERG)was performed to assess retinal function.TUNEL staining was used to detect photoreceptor cell apoptosis in the mouse retinal tissue.Western blot analysis was conducted to measure the expression levels of heme oxygenase-1(HO-1),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X proteins(Bax)in the mouse retinal tissue.Results Compared with those in the Con+group,the amplitudes of the ERG b-wave and the second peak(OS2)of mouse oscillatory potentials(OPs)in BL+,NS+,BL-,N2L-,and NS-groups were decreased significantly under medium-and high-intensity stim-ulating light(all P＜0.05).The cell apoptosis rate and the expression level of Bax proteins in BL+,NS+,BL-,N2L-,and NS-groups were significantly higher than those in the Con+group(all P＜0.05).Compared with those in the BL+group,the amplitudes of the ERG b-wave and OS2 of OPs were increased significantly under medium-and high-intensity stimulating light in N2L+and Con-groups(all P＜0.05).N2L+and Con-groups had a significantly lower cell apopto-sis rate than the BL+group(P＜0.05).BL-and NS-groups had a significantly higher cell apoptosis rate and significant-ly lower Bax levels than the BL+group(all P＜0.05).Compared with those in the N2L+group,the amplitudes of the ERG b-wave and OS2 of OPs were reduced significantly under medium-and high-intensity stimulating light in NS+,BL-,N2L-,and NS-groups(all P＜0.05).The cell apoptosis rate and Bax levels in NS+,BL-,N2L-,and NS-groups were significantly higher than those in the N2L+group(all P＜0.05).The Bax level in the Con-group was significantly lower than that in the N2L+group(P＜0.05).Compared with those in the NS+group,the amplitudes of the ERG b-wave and OS2 of OPs were increased significantly under medium-and high-intensity stimulating light in the Con-group(all P＜0.05).The cell apoptosis rate and Bax levels in the Con-group were significantly lower than those in the NS+group(P＜0.05).Compared with those in the Con-group,the amplitudes of the ERG b-wave and OS2 of OPs were decreased significantly under medium-and high-intensity stimulating light in BL-,N2L-,and NS-groups(all P＜0.05).BL-,N2L-,and NS-groups had a significantly higher cell apoptosis rate and Bax levels than the Con-group(all P＜0.05).HO-1 and Bcl-2 levels in BL+,N2L+,and NS+groups were significantly higher than those in the Con+group(all P＜0.05).Compared with those in the BL+group,HO-1 and Bcl-2 levels were increased significantly in the N2L+group and decreased significantly in Con-,BL-,N2L-,and NS-groups(all P＜0.05).HO-1 and Bcl-2 levels in NS+,Con-,BL-,N2L-,and NS-groups were significantly lower than those in the N2L+group(all P＜0.05).Con-,BL-,N2L-,and NS-groups showed significantly lower HO-1 and Bcl-2 levels than the NS+group(all P＜0.05).The N2L-group had significantly higher HO-1 and Bcl-2 levels than the Con-group(both P＜0.05).Conclusion N2L may antag-onize blue light-induced retinal damage in mice by activating the Nrf2 signaling pathway.

AIM: To investigate the preventive effect and optimal drug dose of lipoic acid-niacin(N2L)against blue light-induced retinal damage in SD rats, and to explore its possible protective mechanism.METHODS: A total of 36 specific pathogen free-grade male SD rats of 150-200 g were selected and randomly divided into normal control group, blue light injury group, N2L low-dose group(1.0 mg/kg), N2L medium-dose group(2.5 mg/kg), N2L high-dose group(5.0 mg/kg), and physiological saline group, with 6 rats in each group. The normal control group was reared in a 12 h dark and light cycle, and the rest of the groups received 9 h of daily light exposure, 3 h of blue light irradiation with a wavelength of 455 nm and an intensity of 3000±50 lx, and 12 h of darkness to establish the injury model, and were exposed to light exposure for 14 d. For 14 consecutive durations, a 1 mL dose of the corresponding drug was injected intraperitoneally. The rats were reared for another 5 d with a regular 12 h light-dark cycle and were examined by electroretinography. Specimens were prepared by over anesthesia, HE staining, and the thickness of the outer nuclear layer was observed under a optical microscope; superoxide dismutases(SOD)activity was detected by CheKineTM SOD Activity Assay Kit; and the retinal Caspase-3, quinone oxidoreductase 1(NQO1), glutathione S transferase(GST), Bcl-2, and Bax protein expression in rat retina were detected by Western blot.RESULTS: The amplitude of b-wave in dark-vision ERG 3.0 and 10.0(cd·s)/m2 stimulated light, b-wave in bright-vision ERG 3.0(cd·s)/m2 stimulated light, and the amplitude of the 2nd wave peak of oscillatory potential were significantly lower in blue light injury group than that in the normal control group(all P<0.01), while the amplitude was significantly higher in the N2L medium-dose group than in the blue light injury group(all P<0.05), and was not statistically different from that of the normal control group; the thickness of the retina in the blue light injury group was decreased in the ONL compared with that of the normal control group(P<0.001), while in the N2L medium dose group, it was thicker than that of the blue light injury group(P<0.001), and there was no statistically significant difference from the normal control group; SOD activity was significantly higher in the N2L medium-dose group than in the remaining 5 groups(P<0.05); the expression of Caspase-3, Bax, and NQO1 in the blue light injury group was higher than that of the normal control group(all P<0.01), and expression of Bax and Caspase-3 was significantly lower in the N2L medium-dose group compared with the blue light injury group(all P<0.001), whereas GST, NQO1 and Bcl-2 were significantly increased(all P<0.01).CONCLUSION:A concentration of 2.5 mg/kg N2L can effectively antagonize the damaging effect of blue light on the retina of SD rats, and it is expected to be a preventive and curative drug for it.