Interleukin-17A attenuates photoreceptor cell apoptosis in streptozotocin-induced diabetic mouse model

ABSTRACT

Diabetic retinopathy (DR) represents an important microvascular complication of diabetes, which is the top etiology of vision impairment worldwide. Although interleukin (IL)-17A is increasingly implicated in DR development, the underlying cellular mechanisms remain poorly defined. This work aims to evaluate IL-17A levels in the retina of streptozotocin (STZ)-induced diabetic mice and elucidate their potential roles. We found IL-17A was upregulated in diabetic retina after intraperitoneal injection of STZ and high-glucose (HG)-cultured primary Müller cells. IL-17A knockout (IL-17A^−/−) downregulated glial fibrillary acidic protein (GFAP) and inhibited the conversion of proneurotrophin-3 (proNT-3) to mature NT-3 in retinal specimens from diabetic mice as well as in Müller cells cultured under HG conditions. Induced apoptosis and upregulated Bax and cleaved caspase-3 were observed in retinal specimens from IL-17A^−/− diabetic mice and photoreceptor (661 W) cells after co-culture with IL-17A^−/− Müller cells. Moreover, RNA interference-induced gene silencing of tyrosine kinase C receptor (TrkC) in 661 W cells reversed the anti-apoptotic effect of IL-17A under HG conditions. Taken together, our findings suggest that IL-17A/NT-3/TrkC axis regulation suppresses apoptosis in photoreceptor cells, providing a new treatment strategy for DR.

GRAPHICAL ABSTRACT

KEYWORDS:

• Interleukin-17
• Müller cells
• neurotrophin-3
• diabetic retinopathy
• apoptosis

Disclosure statement

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

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request (https://doi.org/10.1080/21655979.2022.2084241).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21655979.2022.2084241

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [81970805] and Scientific Research Project of Shanghai Municipal Health Commission [202140183].