The PEDF/PEDF-R axis plays a regulatory role in photoreceptor survival and lipid metabolism

Authors

• SE Crawford
• P Becerra

Abstract

Pigment epithelium-derived factor (PEDF) is essential for photoreceptor survival that acts through its cell-surface receptor, PEDF-R, which also regulates lipid metabolism in the retina. This study investigates the regulatory role of the PEDF/PEDF-R axis in photoreceptors by characterizing mice lacking both PEDF and PEDF-R.
Mice lacking Serpinf1 (PEDF) and Pnpla2 (PEDF-R) genes were generated through crossbreeding. Evaluations were performed in 3 months old mice of mixed sexes. Gene expression was determined by RT-PCR. Histological, immunofluorescence, and confocal microscopy techniques evaluated retinal morphology, and protein expression. Electroretinography (ERG), fundoscopy and autofluorescence angiography assesses retinal function and structure.
Serpinf1+/-/Pnpla2-/- and Serpinf1-/-/Pnpla2-/- mice had decreased and undetectable retinal Serpinf1 gene expression levels, respectively, and both mice lacked Pnpla2 gene expression relative to their Serpinf1+/+/Pnpla2+/+ controls.
Photoreceptors of both mice had thinner outer nuclear layers, decreased rhodopsin and opsin levels, and increased TUNEL positive nuclei. Fundus examination revealed features of white dot syndrome and optic nerve pit disk in double knockout mice. Lipid-related proteins TIP47, BODIPY, and PLIN5 showed altered localization patterns in the retina. Decreased levels of PKCα and synaptophysin were observed in mutant retinas, correlating with attenuated ERG responses.
Ablation of PEDF and PEDF-R in mice leads to early and pronounced defects in photoreceptor morphology, lipid accumulation, and function, surpassing effects seen in single knockout models. These findings highlight the critical role of the PEDF/PEDF-R axis in regulating retinal lipid metabolism and photoreceptor health.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Tuesday, August 6, 2024