XIAP therapy increases survival of transplanted rod precursors in a degenerating host retina.

PURPOSE: To assess the survival of rod precursor cells transplanted into the Rd9 mouse, a model of X-linked retinal degeneration, and the effect of antiapoptotic therapy with X-linked inhibitor of apoptosis (XIAP) on preventing cell loss.
METHODS: Dissociated retinal cells from P4 Nrlp-GFP mice were transplanted into the subretinal space of 2-, 5-, and 8-month-old Rd9 mice. Histology, immunohistochemistry, and quantification of integrated cells were performed every month for up to 3 months after transplantation. XIAP delivery to donor cells was accomplished by transfection with adenoassociated virus (AAV-XIAP). Intraretinal activation of immune modulators was assessed using a quantitative real-time polymerase chain reaction-based immune response array.
RESULTS: GFP-positive rod precursors were able to integrate into the outer nuclear layer (ONL) of the Rd9 retina. Transplanted cells underwent morphologic differentiation with the formation of inner and outer segments and synaptic projections to bipolar cells. Integration of donor cells into the ONL increased as a function of host age at the time of transplantation. The number of integrated cells was maximal at 1 month after transplantation and then decreased with time. Survival of integrated cells was significantly increased when donor cells were pretreated with AAV-XIAP. We did not detect any donor cell-specific activation of inflammation within the host retina.
CONCLUSIONS: Survival of integrated cells decreases with time after transplantation but can be significantly increased with XIAP antiapoptotic therapy. Preventing programmed cell death through XIAP therapy may be an important component of future therapeutic retinal cell transplantation strategies.