Protective effects of pigment epithelium-derived factor against X-ray-induced retinopathy

Abstract

The protective effects of pigment epithelium-derived factor (PEDF) against X-ray-induced retinopathy were investigated in vitro and in vivo. The function of PEDF was suppressed using PEDF receptor inhibitors and transfection of siRNA in human retinal pigment epithelium cell line ARPE-19. The decreased expression of PEDF was measured using quantitative fluorescent reverse transcription PCR and ELISA. Cell viability after X-ray exposure was monitored using the CCK-8 method. Both left and right irradiation fields were set up to deliver X-rays to the eyes of mice using a small animal radiotherapy simulation machine. Each field was irradiated with 10 Gy. The total dose was 20 Gy. The saline containing 2 nmol/L PEDF-34, a 34-amino acid fragment at positions 44~77 of the PEDF, was prepared. After irradiation, the mice were treated with eye drops every day for 4 weeks. After 8 weeks, the eyeballs were harvested for HE and TUNEL staining and checked for retinopathy and apoptosis. The results showed that pretreatment via PEDF receptor inhibitors and the reduction of PEDF expression aggravated X-ray-induced cell damage in ARPE-19 cells, while PEDF-34 exerted protective effects against X-ray-induced cell damage. Eight weeks after irradiation with a dose of 20 Gy, the experimental mice demonstrated aberrant morphology in the retinal pigment epithelial cell layer and apoptotic cells in the outer nuclear layer. The PEDF-34-treated group maintained a structurally normal retina and had no apoptotic cells. The current study indicates that PEDF has a protective effect against radiation-induced retinopathy, and the PEDF-34-containing eye drops could alleviate the injury. Our findings may provide an experimental basis for a new treatment approach for radiation retinopathy.

Keywords

• pigment epithelium-derived factor
• radiation-induced retinal injury
• pigment epithelium cell
• apoptosis