Morphological integration and functional assessment of transplanted neural progenitor cells in healthy and acute ischemic rat eyes

Abstract

We have functionally and morphologically characterized the retina and optic nerve after neural progenitor cell transplants to healthy rat eyes and eyes damaged by acute elevation of intraocular pressure (IOP). Green fluorescent protein-expressing adult rat hippocampal progenitor cells (AHPCs) were transplanted by intravitreal injection into healthy eyes and eyes damaged with acute ocular hypertension. Pupil light reflexes (PLR) and electroretinograms (ERGs) were recorded preoperatively and postoperatively. Eyes were subsequently prepared for immunohistochemical analysis and confocal imaging. Transplanted AHPCs were found in 8 of 15 (53%) acute ischemic eyes 62 days after surgery and 5 of 10 (50%) healthy eyes 32 days after grafting. Analysis of PLR and ERG function in acute ischemic eyes revealed no statistically significant difference compared to controls after transplantation for all observed functional parameters. Transplant into healthy rat eyes revealed no PLR or ERG amplitude deficits between transplanted and non-transplanted (control) eyes. Morphological and immunohistochemical analysis revealed that transplanted AHPCs survived and differentiated in both normal and injured retinal environments. Morphological integration occurred primarily within the inner retinal layers of the acute ischemic eyes. AHPCs were found to express neuronal and glial markers following transplantation. Transplanted AHPCs have the ability to integrate and differentiate in ischemia damaged retinas. PLR and ERG analysis revealed no significant difference in functional outcome in transplant recipient eyes.