PEDF receptors and VEGFR-1 are involved in the protection of retinal neurons

Author: Jie Meng (Germany)

Co-authors: Susanne Bürger, Annette Zwanzig, Maik Pankonin, Peter Wiedemann, Jan Darius Unterlauft, Wolfram Eichler

Purpose

The purpose of this study was to determine regulation of PEDF receptors (PEDFR and Laminin R) and VEGFR-1, by retinal ganglion cells (RGC) under hypoxia, which is a relevant pathological condition in retinal neurodegenerative diseases such as glaucoma or ischemic retinopathies. Changes in the expression of some neuron protective factors, such as PEDF and VEGF, when reducing the expression of PEDF receptors and VEGFR-1. In addition, we have explored the impact of all the receptors on the viability of retinal neuronal cells.

Setting/Venue

Department of Ophthalmology and Eye Hospital, Leipzig University, Germany

Methods

Using RGC isolated from mice eyeballs and the immortalized retinal cell line R28 as the main research objects. Immunocytochemical Staining, RNA Interference, qPCR, and western blot techniques, were used to detect the expression levels of PEDF-R, Laminin-R and VEGFR-1 under different stimulations. After knocking out PEDF-R, Laminin R and VEGFR-1 genes with interfering RNA, the expression level of neuroprotective factors and anti-apoptotic Bcl-2 family-related factors were detected.

Results

The PEDF receptors and VEGFR-1 are co-expressed in RGC and R28 Cells. Complex secretions from Müller cells enhance expression of PEDF receptors and VEGFR-1 in R28 Cells under Hypoxia. The mRNA expression levels of PEDF-R, Laminin R and VEGFR-1 in RGC and R28 cells are significantly increased after exposure to PEDF, VEGF and hypoxia. Expression of pro-survival factors and neuronal survival are under control of PEDF-R, LR and VEGFR-1.

Conlusions

Upregulation of PEDF-R, Laminin R and VEGFR-1 under hypoxia sensitizes retinal neurons to interaction with PEDF, which leads to increased cell viability through induction of anti-apoptotic Bcl-2 family members, expression of secretable pro-survival factors, and suppression of apoptosis. Elucidating PEDF-R, Laminin R and VEGFR-1 function and signaling pathways regulating receptor-promoted RGC survival may be helpful in developing more efficient treatment options for retinal neurodegenerative diseases.

Financial Disclosure

This research was funded by Deutsche Forschungsgemeinschaft, grant number UN 37512, and Geschwister Freter Stiftung (Hannover). A.Z. gratefully acknowledges financial support by an intramural program of the Medical Faculty, University of Leipzig. The authors declare no conflict of interest.