Salidroside Inhibits Ganglion Cell Apoptosis by Suppressing the Müller Cell Inflammatory Response in Diabetic Retinopathy

Abstract

Purpose

This study aimed to investigate the role of salidroside (SAL) in the cellular communication between Müller cells and retinal ganglion cells in diabetic mice.

Methods

The diabetes mellitus (DM) animal models were established by the intraperitoneal injection of streptozotocin and treatment with SAL via gavage or by the injection of IL-22BP into the vitreous cavity. Immunohistochemistry was used to measure the expression of the glial fibrillary acidic protein in Müller cells. The expression of IL-22 and IL-22Rα1 in retinal tissues was assessed by immunofluorescence. Western blotting was used to measure the expression of inflammatory and apoptosis-related proteins. Hematoxylin–eosin staining, TUNEL staining, and flow cytometry were used to analyze the apoptosis of retinal ganglion cells. The effect of cellular interactions was explored by Transwell assays.

Results

Western blotting showed that glial fibrillary acidic protein, IL-22 protein expression was significantly upregulated in the DM animal models compared with the control mice. Immunofluorescence showed that IL-22 was highly expressed in Müller cells and IL-22Rα1 was expressed in ganglion cells in the retina of DM mice. Hematoxylin–eosin and TUNEL staining results showed an increase in the number of ganglion cells apoptotic in DM. However, SAL reversed these phenomena. Meanwhile, after coculture with Müller cells, Western blotting suggested that ganglion cells secreted p-STAT3, and c-caspase3 protein expression was increased. More interestingly, the treatment of IL-22BP and SAL inhibited the expression of the p-STAT3 and c-caspase3 proteins. Flow cytometry indicates that compared with the control group, the apoptosis rate of ganglion cells was increased in the high glucose group, while the apoptosis rate of cells in the recombinant IL-22 protein group was significantly increased, while the SAL inhibited ganglion cells apoptosis.

Conclusion

SAL inhibits the apoptosis of retinal ganglion cells via the IL-22/STAT3 pathway in Müller cells.

Keywords:

• Diabetic retinopathy
• Müller cells
• retinal ganglion cells
• IL-22
• salidroside

Author contributions

J.L. and W.Q.L. contributed to experiments, data collection, manuscript writing. Y.F.W. and A.Q.L. provided help for experimental testing and theoretical support. S.X.Y. and H.D.Y. helped to collect experimental data. X.Z.L. and Z.F.Z. contributed to experimental conception, data interpretation, and manuscript revision. All authors have read and approved the submission and publication of the final version of manuscript. The authors vouch for the accuracy and completeness of the experiment.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All relevant data generated or analyzed during this study are included in this published article.

Additional information

Funding

This study was supported by National Natural Science Foundation of China [No. 81571383] and China Postdoctoral Science Foundation [No. 2017M612870].