Inhibition of P2X7R Activation Ameliorates Damage to the Corneas and Corneal Nerves of Rats with Streptozotocin (STZ)-Induced Type 1 Diabetes.

Abstract

Purpose: To investigate the effect of the P2X7 receptor (P2X7R) to the corneas and corneal nerves of rats with streptozotocin (STZ)-induced type 1 diabetes as well as the underlying mechanism.

Methods: In this study, male Wistar rats were first randomly divided into normal group (NL) and diabetes group (DM). After intraperitoneal injection of STZ, corneal perception, corneal fluorescein staining and the expression of P2X7R mRNA and protein in corneal tissues of NL and DM groups were detected before, 4, 6, 8, 12 and 16 weeks respectively. Then male Wistar rats were randomly divided into NL group, DM group and P2X7R inhibitor group (BBG). Start at 2 weeks after diabetes modeling, the BBG group was intraperitoneally injected with BBG every day. Corneal perception, corneal fluorescein staining, in vivo confocal microscopy, laser scanning confocal microscopy, corneal P2X7RmRNA levels, the mRNA levels of Brain-derived neurotrophic factor (BDNF), Glial cell-derived neurotrophic factor (GDNF), Nerve growth factor (NGF), Neuropeptide Y (NPY) and Growth associated protein-43(GAP-43) of corneal and trigeminal nerve were detected in the three groups at the 6th and 8th week.

Results: The mRNA and protein expression of P2X7R was significantly increased as early as 6 weeks after STZ injection and then showing a downward trend, but the corneal perception and corneal fluorescent staining continued to worse. Inhibition of P2X7R activation increased corneal sensitivity, ameliorated corneal epithelial damage, improved corneal subbasal nerve plexus density and length, increased the expression of BDNF in the trigeminal nerve and increased the expression of NPY in the corneal and trigeminal nerves.

Conclusions: The increase of P2X7R expression of diabetic rats was not synchronized with the gradually aggravated corneal injure. Inhibition of P2X7R activation can alleviate diabetes-associated corneal injury, regulate the expression of related neurotrophic factors and neuropeptides, and improve the corneal subbasal nerve plexus.