Resveratrol inhibits neural apoptosis and regulates RAX/P-PKR expression in retina of diabetic rats

ABSTRACT

Purpose

This study was to investigate the effect of resveratrol (RSV) administration on diabetes-induced neural apoptosis and on RNA-dependent-protein-kinase (PKR)-associated protein X (RAX), PKR and phosphorylated PKR (P-PKR) expression and distribution in retina of diabetic rats.

Methods

Retina was obtained from normal and diabetic Sprague–Dawley rats with or without RSV (5 and 10 mg/kg/d) treatment at 30-, 32-, 34- and 36-weeks. Apoptosis of retinal neural cells and distribution of RAX/P-PKR was assessed by TUNEL and immunofluorescence methods. Expression of RAX, PKR and P-PKR was evaluated by qRT-PCR and western-blotting methods.

Results

Our study showed that the TUNEL-positive cells were mainly localized in ganglion cells layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL) of the diabetic rat's retina at 30-, 32-, 34- and 36-weeks. RSV administration effectively suppressed the neural apoptosis in GCL, INL and ONL. Almost no TUNEL-positive cells were observed in retina of normal control and RSV-treated normal control rats. Our study also showed that the expression level of RAX, P-PKR in diabetic rats retina at 30-, 32-, 34-, and 36-weeks was elevated. With supplementation of 5 and 10 mg/kg/d RSV, the expression level of RAX and P-PKR was decreased (P < 0.05). The expression level of RAX and P-PKR in the retina of normal control rats was not altered by RSV. The expression level of PKR was not altered by streptozotocin injection and RSV treatment.

Conclusions

Our results suggested that RSV attenuates retinal neural apoptosis in diabetic rats retina may be via regulation RAX/P-PKR expression.

KEYWORDS:

• Resveratrol
• neural apoptosis
• diabetic retinopathy
• RNA-dependent-protein-kinase-associated protein X (RAX)
• RNA-dependent-protein-kinase (PKR)
• phosphorylated PKR (P-PKR)
• ganglion cells layer (GCL)
• inner nuclear layer (INL)
• outer nuclear layer (ONL)

Acknowledgments

This work is supported by the National Natural Science Foundation of China (grant 81202206). This work is also supported by the Health and Family Planning Commission Foundation of Sichuan, China (grant 150216).

Disclosure statement

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

Additional information

Funding

This work was supported by National Natural Science Foundation of China: [grant number 81202206]; Health and Family Planning Commission of Sichuan Province Project: [grant number 150216].