Neurons have been successfully grafted into several sites in the central nervous system (CNS), including the striatum, hippocampus and olfactory system, making this a promising approach for treatment of neural diseases or injury. However, attempts to repopulate damaged retina with grafted neurons have been unsuccessful. In the September issue of Molecular and Cellular Neuroscience, Young et al. demonstrate that neuronal progenitor cells, derived from adult rat hippocampus, are capable of integrating into retinas in a rat model of retinal dystrophy.

Neuronal progenitor cells exist in the adult hippocampus of rodents, monkeys, and humans. Adult hippocampal progenitor cells (AHPC) have been isolated from rats and shown to differentiate into neurons when grafted into the CNS. Young et al. isolated AHPC, labeled them with green fluorescent protein (GFP), and injected them into the vitreous of immature and mature dystrophic rats. The grafted cells were able to migrate within the dystrophic retina and then differentiate into mature neurons in one-, four-, and ten-week-old rats. GFP-labeled cells were also observed to extend neurites into the host optic nerve. The image shows grafted GFP-expressing AHPC (green) integrating and sending processes into the plexiform (synaptic) layers of the retina, labeled with antibodies against synaptophysin (red).

The AHPC were only able to integrate in animals with retinal disease or injury, suggesting that the ability to integrate and differentiate is enhanced, rather than suppressed by injury. The AHPC also failed to enter the retina or survive when transplanted into the eyes of 38-week-old rats, suggesting that there is loss of trophic support late in the course of dystrophy. “We're testing whether the grafted stem cells establish functional connections with the host visual system, and whether these connections convey useful visual information,” says Young. The authors also hope to investigate the immunological properties of AHPC and to determine whether they exhibit immune privilege after transplantation.

This approach may someday be used to treat human diseases of the optic nerve and retina such as glaucoma, macular degeneration, retinitis pigmentosa, retinal detachment, and diabetic retinopathy. However, neural progenitor stem cells must first be isolated from human CNS and determined to have the same qualities as the rat AHPC. “We also have to optimize transplantation techniques that would allow us to reconstruct the layers of the retina in patients,” adds Young.