Combining chondroitinase ABC and growth factors promotes the integration of murine retinal progenitor cells transplanted into Rho−/− mice

PURPOSE The aim of this study is to investigate the synergistic effect of chondroitinase ABC and growth factors in the integration of murine retinal progenitor cells (mRPCs) transplanted into Rho(-/-) mice. METHODS mRPCs from P1 green fluorescent protein-transgenic mice were isolated and expanded for transplantation. All mRPCs of 20 passages or less were transplanted into the subretinal space of B6 mice together with chondroitinase ABC, and into Rho(-/-) mice combined with chondroitinase ABC, N-[N-(3, 5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), and insulin growth factor (IGF)-1. Cell counts were used to examine the migration and survival rate of mRPCs in B6 mice. Immunohistochemistry was used to evaluate the differentiation and integration of mRPCs in B6 and Rho(-/-) mice. RESULTS Our results show that substantial numbers of mRPCs migrated and survived in the retina when transplanted with chondroitinase ABC into B6 and Rho(-/-) mice. Chondroitinase ABC disrupted the glial scar around the mRPCs in the subretinal space. Only a few mRPCs expressed recoverin in B6 mice. More mRPCs expressed rhodopsin, recoverin, and synaptophysin after transplantation into Rho(-/-) mice when combined with chondroitinase ABC and growth factors. CONCLUSIONS The synergistic effect of chondroitinase ABC and growth factors facilitates the anatomic integration of mRPCs transplanted into Rho(-/-) mice.