Functional and morphological assessment of chronic hypertensive rat eyes after neural progenitor cell transplantation

Abstract

Abstract: : Purpose: To functionally and morphologically characterize the rat retina and optic nerve after neural progenitor/stem cell (NPC) transplantation in chronic hypertensive rat eyes by using electroretinography (ERG) and automated pupillometry. Methods: Chronic ocular hypertension was induced in 7 Brown Norway rats by laser cauterization of the trabecular meshwork and GFP–expressing adult rat hippocampal–derived progenitor cells were transplanted by intraocular injection 50 days after surgery. Direct and indirect pupil light reflexes (PLR) were recorded from the unoperated eye, and ERGs were recorded from the operated and control eyes preoperatively, postoperatively and after NPC transplantation. Thirty days after transplantation, rats were euthanized and eyes were subsequently prepared for immunohistochemical analysis. Results: Laser treatment induced significant elevation of the IOP in operated eyes and caused complete loss of retina and optic nerve function 50 days postoperatively. Transplanted NPCs were detected in 2 of 7 chronic hypertensive rat eyes 30 days after transplant. Chronic ocular hypertensive eyes, which received NPC transplants at day 51 postoperatively, showed no signficant recovery of the PLR function after stimulating operated eyes. The PLR_{ratio (operated/control)} was 0.62+0.5% fifteen days after transplantation and was not significantly different compared to pre–transplant values (p>0.1, Repeated measures ANOVA with Bonferroni posttest). Thirty days after transplantation the PLR_ratio was 1.3+1.2% and again was not significantly different compared to pre–transplant values (p>0.1, Repeated measures ANOVA with Bonferroni posttest). ERG amplitudes (a– and b–wave, flicker ERG) did not show significant recovery compared to the pre–transplant values. Morphological integration and differentiation of transplanted cells occurred primarily within the inner retinal layers. Conclusions: Based on ERG and PLR analysis, and under the conditions used in the present study, no evidence for protection or recovery of function to damaged retinas and optic nerves was observed after transplantation of adult neural progenitor cells in chronic hypertensive rat eyes. Efforts are under way to improve the functional recovery of transplanted progenitor/stem cells in our rat model.

Keywords: intraocular pressure • transplantation • electroretinography: non–clinical