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Amanda C. Barber, Claire Hippert, Jane C. Sowden, Robin R. Ali, Rachael A. Pearson; Retinal Repair In The Degenerating Retina: Assessing Photoreceptor Transplantation In Models Of Retinal Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4019.
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© ARVO (1962-2015); The Authors (2016-present)
Cell transplantation is a potential therapeutic strategy for the irreversible loss of photoreceptors occurring in retinal degeneration. Transplanted rod precursor cells can integrate into the degenerating retina & restore a basic visual response. We examined whether integration efficiency changes in different models of retinal degeneration & whether disease progression of the recipient retina impacts upon integration.
Integration was compared in several mouse models of retinal degeneration: rho-/-, Crb1rd8/rd8, Prph2rds/rds, Rds-307+/-, & GNAT1-/-. FACS-sorted rod precursors were isolated from P4 Nrl.gfp retinae & transplanted into recipients at early, mid & late degenerative states. Integrated cells were counted 3 weeks post-transplantation. Glial scarring, chondroitin sulphate proteoglycan deposition, outer nuclear layer thinning & outer limiting membrane (OLM) integrity were also assessed.
Integration efficiency varied considerably between different models. At 6 weeks of age, the highest integration achieved was in the Crb1rd8/rd8 mouse with a mean of 10,774 integrated cells, this was ~17 fold lower in the rho-/-recipient. Integration in the Prph2rds/rds, Rds-307+/-, GNAT1-/- & wildtype was statistically similar, ranging from a mean of 3069 in the Rds-307+/- to 5067 integrated cells in the Prph2rds/rds recipients. Surprisingly, integration increased with disease progression in the Rds-307+/- rising to a mean of 9534 integrated cells in the 6 month recipient. However, integration declined in the rho-/-. Transplanted photoreceptor morphology was also affected by the recipient environment; poor outer segment (OS) morphology was observed in recipient models with no/poor endogenous OS development (rho-/-, Prph2rds/rds), whereas good OS formation was observed in the GNAT1-/- recipient.
For the first time we show that integration efficiency & transplanted photoreceptor morphology are not equivalent in different degenerative models. Clinically, this may prove important for the breadth of application of cell therapy. Disease progression has a major impact on integration efficiency &, importantly, can prove favorable to transplantation success, suggesting that cell therapy could treat end stage disease. The glial scar & OLM appear to be major determinants hindering integration success. Thus, the aetiology of an individual retinal degeneration should be considered when developing transplantation strategies.
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