关键词: NADPH氧化酶2, rd1小鼠, 小胶质细胞活化, 视网膜变性, 感光细胞保护

Abstract: Objective To observe the delay of photoreceptor degeneration in the NADPH oxidase2 (NOX2) deficiency-rd1 mice. Design Experiment study. Participants 6 NOX2-deficiency rd1 mice (experimental group) at postnatal 14d and their control groups at same age, including 6 NOX2-deficiency C57BL/6N mice (control group 1), 6 rd1 mice without NOX2-deficiency (control group 2) and 6 C57BL/6N mice (control group 3) were included. Methods The experimental group were obtained and appraised through repeated mating of control group 1 and control group 2 mice. The thickness of outer nuclear layer (ONL) was measured on HE staining. Photoreceptor apoptosis was examined by TUNEL assay and the percentage of apoptotic cells in total cells of ONL was counted. The expression of gp91phox, a major subunit of NOX2, as well as activation of microglial cells were studied by immunofluorescence and double-labeling technique. Main Outcome Measures Thickness of outer nuclear layer; percentage of TUNEL positive cells; expression of gp91phox; microglial activation. Results In the experimental group, the thickness of outer nuclear layer was 36.18±2.59 μm, which was significantly higher than that of control group 2 (21.45±1.33 μm, t=8.77, P=0.001). TUNEL positive retinal apoptotic cells, which mainly appeared in the ONL of experimental group, were markedly reduced（t=8.46, P<0.001） when compared with aged matched control group 2. Compared with control group 3 and control group 1, microglial cells were markedly activated in the retina of control group 2 and infiltrated ONL. Expression of gp91phox was also increased in part of microglial cells. In contrast, the experimental group showed dramatically down-regulated expression of both gp91phox and activation of microglial cells. Conclusion Deficiency of NOX2 gene effectively delayed photoreceptor cell loss in the rd1 mice possibly through inhibition of microglial cells. NOX2 may become a new and potential therapeutic target for inherited retinal degeneration. （Ophthalmol CHN, 2022, 31: 140-145）

Key words: NADPH oxidase 2, rd1 mice, microglial activation, retinal degeneration, photoreceptor protection