Neural Stem Cells Rescue Behavioral and Electrophysiological Responses in a Rat Model of Retinal Pigment Epithelium Loss

Abstract

Purpose: : To characterize the behavioral and electrophysiological changes in rats after retinal pigment epithelium(RPE) loss created by the intravenous (i.v.) administration of sodium iodate (NaIO₃) and subretinal transplantation of neural stem cells (NSC).

Methods: : 2% NaIO₃ was injected i.v. into Lewis rats (200–250 g) with a single injection of 70 mg/ kg body weight. Three days later 30,000 GFP⁺ NSC in 4 µl buffer were transplanted into the subretinal space using an ab externo approach (n = 13). The NSC were prepared from embryonic day 14 old rat cortex, cultured and transfected with GFP using a retroviral vector (pLZRSEGFP). Sham surgery was performed (n = 13) with the subretinal injection of an equal volume of buffer in NaIO₃ treated animals that served as controls (n = 15). Before treatment, as well as 1, 2, and 3 months after transplantation, a cued water maze test was performed to analyze vision–dependent behavior. Furthermore, a scotopic and photopic electroretinogram (ERG) was recorded before treatment and 3 months after transplantation. H&E staining and immunohistochemistry were performed on paraffin sections of the enucleated eyes to visualize the transplanted NSC and to observe the overall changes in the retinal gross anatomy.

Results: : With 70 mg/kg NaIO₃ a patchy loss of RPE was observed and a monolayer of GFP⁺ NSC could be visualized in the subretinal space after NSC transplantation. Path length and latency in the water maze significantly decreased and the b–wave amplitude in the photopic ERG was significantly higher in the transplanted group compared to both control groups (NaIO₃ alone; NaIO₃ + shame surgery) after the treatment (P < 0.05).

Conclusions: : In a rat model of RPE loss, improvement of visual function after transplantation of NSC was confirmed by behavioral and electrophysiological measurements. This opens the possibility of the use of NSC transplantation as a therapy for eye diseases with RPE loss.

Keywords: electrophysiology: non-clinical • retinal degenerations: cell biology • transplantation