Interleukin-17A attenuates photoreceptor cell apoptosis in streptozotocin-induced diabetic mouse model.
Bioengineered
; 13(6): 14175-14187, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35730427
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.
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Experimental
/
Retinopatia Diabética
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article