Regenerative Stem Cell Therapy In Retinal Degeneration |

ABSTRACT:

Stemcell-based therapy has been tested for several diseases, includingneurodegenerative disorders, such as Parkinson’s disease, spinal cord injury,and multiple sclerosis in animal models. The replacement of lost neurons thatare not physiologically replaced is pivotal for therapeutic success. In theeye, degeneration of neural cells in the retina are hallmarks of suchwide-spread ocular diseases as AMD and RP. In these cases the primary cause ofblindness is due to loss of photoreceptors. This can result from dysfunction ineither the PRC or the underlying RPE that supports their survival.  Transplantation ofRSC with the potential to generate new retinal cells provides an alternativeapproach to enable the replacement of lost PRC or RPE. Retinal stem cells mayrestore vision in patients who have degenerative retinal diseases by twopossible means: 1) repopulation of the damaged retina (e.g., PRC); and/or 2)rescue of retinal neurons from further degeneration.80Different research groups have successfully isolated murine putative RSC fromthe ciliary margin (CM) and human RSC in the pars plana and pars plicata.81,82However, the transplantation of these cells in normal and degenerative rodentretina was only minimally successful due to the limited ability of the cells toinvade and integrate into the host retina.27On the other hand, transplantation of immature post-mitotic rod precursors fromdeveloping retina (postnatal day 1) improves retinal integration.83The optimal result occurs when selected cells were biochemically committed butnot yet morphologically differentiated. The capability of subretinally orintravitreously injected RSC to invade and integrate into the neural retinaremains restricted to sites of retinal injury. Breakdown of physical barriers,such as the outer limiting membrane, and/or release of unknown neurotrophicfactors, are most likely required to stimulate RSC integration.84To date only sparse data are available regarding factors that might stimulatemigration, integration, and differentiation of RSC into the neural retina.