Purchase this article with an account.
DM Chacko, X Zhao, AV Das, J James, S Bhattacharya, I Ahmad; Injury Promotes Incoporation Of Transplanted Neural Stem Cells/Progenitors In The Host Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3895.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously shown that retinal stem cells/progenitors, transplanted in the subretinal space of normal rats, survive and differentiate into cells of photoreceptor lineage (Chacko et al., 2000, Biochem. Biophys. Res. Commun. 268: 842-846). However, the incorporation of the graft in the host retina remained modest. Here we wanted to analyze injury, mechanical or genetic, as a prerequisite for the incorporation of grafts in the host retina. Methods: Subretinal and vitreal transplantation was carried out on P23H transgenic rats and on those with mechanical injury to the retina. Transplant reagents included neural progenitors from three different sources, i.e., embryonic retina (ER), adult ciliary body (CB) and adult corneal limbal epithelium (LE), to rule out that the phenomenon of incorporation was not cell-specific. Neural stem cells/progenitors were expanded in vitro in the presence of mitogens and labeled with the green fluorescent protein (GFP) or 5(6)CFDA before transplantation. Eyes were enucleated from perfused fixed animals and cyosectioned. Sections were screened for the presence of grafts and subjected to immunocytochemical analysis with cell type-specific markers. Results: Neural stem cells/progenitors, transplanted subretinally and intravitreally, survived in both normal and injured rats. A subset of cells in the ER and CB grafts expressed photoreceptor-specific markers suggesting their potential to differentiate into photoreceptors in the host retina. Cells with photoreceptor-specific markers were not detected in LE grafts. However, a subset of cells in LE grafts expressed pan neuronal markers. All three types of grafts, placed either subretinally or intravitreally, showed incorporation in the injured host retina. However, the levels of incorporation were higher with intravitreal transplantation. In addition, the levels of incorporation were higher in the inner retina than in the outer retina. The order of levels of incorporation was as follows: inner nuclear layer ≷ganglion cell layer≷ outernuclear layer. Conclusion: Injury, mechanical or genetic, is one of the important determinants of incorporation of transplanted neural stem cells/progenitors in the host retina. However, it does not ensure a uniform incorporation in the lamina of the retina. Supported by Foundation Fighting Blindness.
This PDF is available to Subscribers Only