The involvement of the mGluR5-mediated JNK signaling pathway in rats with diabetic retinopathy

Abstract

Objective: To understand the involvement of the mGluR5-mediated JNK signaling pathway in rats with diabetic retinopathy (DR).

Methods: This study established rat models of diabetes mellitus (DM), which were divided into Normal, DM, DM + CHPG (mGluR5 agonist CHPG), and DM + MTEP (mGluR5 antagonist MTEP) groups. The blood glucose and weight of rats were recorded. EB staining was used for observation of blood-retinal barrier (BRB) damage. Neural retina function was measured by pattern electroretinogram (ERG). PAS and NG2 immunohistochemistry were conducted to evaluate the retinal vascular morphology. The TUNEL assay and active caspase-3 immunohistochemistry were performed to detect retinal cell apoptosis. Additionally, the expression levels of superoxide dismutase (SOD) and methylenedioxyamphetamine (MDA) were measured. Moreover, expression levels of mGluR5 and JNK pathway-related proteins were detected by western blot.

Results: When compared with control rats, rats in the DM group showed decreased amplitude and latency of the peak times in the ERG test; further, DM group rats presented increases in blood glucose, BRB permeability, a retinal capillary area density, retinal cell apoptosis with an increased number of active caspase-3-positive cells, MDA level, mGluR5 levels, and the ratio of p-JNK/JNK, and they showed reductions in body weight and SOD activity, as well as in the number of pericytes and in the pericyte coverage (all P < 0.05). However, rats in DM + CHPG group had stronger negative effects than those in DM group (all P < 0.05). Rats from DM + MTEP group showed an opposite trend compared with the DM rats (all P < 0.05).

Conclusion: The level of mGluR5 in DR rats was upregulated, whereas inhibition of mGluR5 alleviated retinal pathological damage and decreased cell apoptosis to improve DR via suppression of the JNK signaling pathway, which provided a scientific theoretical basis for the clinical treatment of DR.

Keywords: Apoptosis; Diabetes mellitus; Diabetic retinopathy; JNK signaling pathway; mGluR5.