Development of stem cell therapy for the treatment of retinal degeneration
Retinal degenerations leading to loss of photoreceptors are a major cause of untreatable blindness in the UK. Inherited retinal dystrophies affect 1 in 3,000 of the population, and age-related macular degeneration (AMD) affects 1 in 10 people over 60 yrs. Currently no treatments restore lost photoreceptor cells and visual function and thus there is a need for new therapeutic approaches. As new photoreceptors need only make short, single synaptic connections to the inner retinal circuitry to contribute to visual function, retinal repair by photoreceptor transplantation represents one of the most feasible types of CNS repair. We have previously discovered that transplantation of photoreceptor precursor cells at a specific stage of development results in their integration and subsequent differentiation into photoreceptors that form synaptic connections (Maclaren et al Nature 2006). We have also recently demonstrated improvements in vision following transplantation in mice with visual deficits. In this talk I will present this work and outline the many challenges of developing stem-cell derived photoreceptor transplantation for the treatment of retinal disorders and how we are addressing these issues.
References
Effective transplantation of photoreceptor precursor cells selected via cell surface antigen expression Lakowski J, Y-T Han, Pearson RA, Hubank M, Ali RR, Sowden JC. Stem Cells. 2011 (in press)
Long term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation. EL West, RA Pearson, SE Barker, UF Luhmann, RE MacLaren, AC Barber, Y Duran, AJ Smith, JC Sowden and RR Ali. Stem Cells. 2010; 28 (11): 1997-2007
Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair fail to differentiate into new rod photoreceptors. Gualdoni S, Baron M, Lakowski J, Decembrini S, Smith A, Pearson R, Ali RR Sowden J. Stem Cells 2010; 28 (6): 1048-59.
Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wildtype and degenerating retina. RA Pearson, AC Barber, EL West, RE MacLaren, Y Duran, JW Bainbridge, JC Sowden and RR Ali Cell Transplantation 2010; 19 (4): 487-503
Retinal repair by transplantation of photoreceptor precursors. RE MacLaren, RA Pearson, A MacNeil, RH Douglas, TE Salt, M Akimoto, A Swaroop, JC Sowden and RR Ali Nature 2006; 444 (7116): 203-207.