[The HMGB1, caspase-1 and gasdermin D-mediated pyroptosis in high-altitude retinopathy: an experimental study]

Objective: To investigate the role of high mobility group protein B1 (HMGB1), cysteine aspartic protease 1 (caspase-1) and gasdermin D in the pathogenesis of high altitude retinopathy (HAR). Methods: This study is an experimental research. Twelve 8- to 10-week-old male c57BL/6J mice without a specific pathogen grade were randomly divided into the HAR group (HAR model) and control group (normal pressure and oxygen environment) according to the random number table method. Hematoxylin-eosin staining was used to observe the histopathological morphology of the mouse retina, and immunofluorescence staining was used to detect the distribution and expression of HMGB1, caspase-1 and gasdermin D in the mouse retina. The relative expression levels of HMGB1, caspase-1 and gasdermin D proteins in the mouse retina were detected by Western blot. Independent sample t test was used for statistical analysis. Results: Hematoxylin-eosin staining showed that compared with the control group, the retinal nerve fiber layer in the HAR group was thickened, the ganglion cell layer was swollen significantly, the intercellular edema in the inner nuclear layer was increased significantly, and the outer nuclear layer distance was loosened. Immunofluorescence staining results showed that HMGB1 expression in the retina of mice in the HAR group was higher than that in the control group, and it was mainly in the ganglion cell layer, inner nuclear layer and outer nuclear layer. Caspase-1 and gasdermin D expressions in the retina of mice in the HAR group were higher than those in the control group, and they were mainly in the ganglion cell layer, inner plexiform layer and outer plexiform layer. The immunofluorescence values of HMGB1, caspase-1 and gasdermin D in the HAR group [(116.8±62.92), (104.7±13.81) and (95.43±10.72) arbitrary fluorescence units] were higher than those in the control group [(52.93±30.08), (66.00±15.19) and (62.54±16.36) arbitrary fluorescence units]. The differences were statistically significant (all P<0.05). The results of the Western blot test showed that the gray band values of HMGB1, caspase-1 and gasdermin D proteins in the retina of HAR group (1.134±0.060, 1.598±0.165 and 1.422±0.142) were higher than those in the retina of control group (1.000±0.021, 1.000±0.155 and 1.000±0.218), with statistically significant differences (all P<0.05). Conclusions: The expressions of HMGB1, caspase-1 and gasdermin D were significantly increased in the retina of HAR mice. HMGB1-mediated pyroptosis in the retinal tissue of HAR mice through the caspase-1/gasdermin D signaling pathway led to retinal structure destruction and the occurrence or development of HAR.