Purpose: Stem cell transplantation has the potential for treating a number of neurodegenerative disorders, including those affecting the retina. To develop stem cell transplantation as a therapy for retinal degeneration, protocols will need to be optimized using animal models. Toward this end, studies were undertaken to determine the fates of neural/glial precursor cells transplanted into the eyes of mice with hereditary retinal degenerations.
Methods: Mouse embryonic stem cells expressing enhanced green fluorescent protein (EGFP) were subjected to retinoic acid treatment in vitro to induce them to differentiate into neural/glial precursors. Immnuolabeling confirmed that retinoic acid treatment induced the expression of neuronal and glial marker proteins. The neural/glial precursors were injected into the vitreous of both CBA/J and mnd mice at 6 to 7 weeks of age. The fates of the transplanted cells were monitored with fluorescence microscopy and immunocytochemistry. Retinal function was monitored with ERG recordings.
Results: A fraction of the transplanted cells migrated into the retinas in both mouse models. Many of the transplanted cells differentiated into neurons and glia based on both morphological and immunostaining criteria. Relative to normal controls, visual sensitivity in the mnd mice is about 2.5 log units lower at 6 weeks of age as determined by the ERG. Improvements in ERG responses were observed in stem cell injected eyes relative to sham-injected eyes.
Conclusion: Stem cell-derived neural/glial precursors can be transplanted into the eye where they undergo differentiation and survive for long periods. Cells transplanted in this manner have great potential for treating certain types of retinal degeneration.