Differentiation of Systematically Injected Mesenchymal Stem Cells into Retina Cells in the Rat Eye.

Presently, no effective treatment are available for retinal degeneration but there are a number of lines of investigation which suggest potential approaches. A number of investigations have shown the multilineage potential of mesenchymal stem cells (MSCs) into neural lineages, which prompted us to attempt their induction into photoreceptors. We evaluated whether systematically injected bone marrow-derived MSCs can be incorporated into the neuroretinal tissues and play an important role in healing retinal wound in the laser-induced retinal trauma model. After Nd;YAG laser-induced retinotomies, MSCs prelabeled with GFP were injected via tail vein. The fundus photographs were taken serially, and eyeballs were enucleated for histological studies. In ophthalmic examination, MSCs injected retinas were showed no hemorrhage, retinal detachment, and vitreous opacity at 4 weeks after MSCs injection. At same time, GFP(+) pigmented cells were detected at the damaged sites and observed more plentiful at the base of the laser-induced break sites. In time-dependent manner, more GFP(+) cells were detected around the damaged retina and incorporated into the neuroretinal tissues through the systemic route. We performed immunohistochemical analyses to evaluate the differential potential of MSCs into neuron. Although retinas were rarely stained within 4 weeks, MSCs injected retinas were consistently and strongly stained after 4 weeks in proportion to the amount of MSCs to engraft into retinas. To test whether MSCs treatment could also induced functional rescue of vision in injured rats, we performed electroretinograms on rat 4 weeks after MSCs injection. Detectable, albeit subnormal, electroretinogram recordings are observed in MSCs injected eyes. However, in all cases electroretinogram from the control eyes was non-detectable. Overall, these results are suggestive of some degree of functional rescue in MSCs injected eyes. Conclusively, we demonstrated the successful transplantation of ex vivo expanded MSCs with minimal side effects when injected intravenously into injured rat retina; we also showed the in vivo survival of these cells, their partial integration, and differentiation into the host retina.