Abstract
Abstract: :
Purpose: There are indications that glial structures/molecules contribute to the formation of a barrier at the graft–host interface, limiting integration of subretinal transplants. In the present study, we have examined the integration between developing retinas and retinas derived from glial fibrillary acidic protein (GFAP) and vimentin (vim) deficient animals with photoreceptor degeneration. Methods: Fragmented retinal tissue obtained from mice expressing green fluorescent protein (GFP, 5 days old) was transplanted into the subretinal space of adult GFAP–vim knockout mice harboring an rd mutation (rdGFAP–/–vim–/–) and of matched wild–type controls to GFAP–/–vim–/– mice (rdGFAP+/+vim+/+). Transplants were examined after 7 and 14 days. The presence of CD44, a Müller glial cell–associated protein expressed at the level of the outer limiting membrane, was examined by immunohistochemistry. Graft–host integration was established by the occurrence of GFP+ bridging fibers and of GFP+ cells within the host retina. Results: Migration of GFP+ cells and extension of GFP+ fibers into the abutting rd retina were observed in all groups. However, integration was seen only in places where CD44 immunoreactivity along the outer limiting membrane of the host rd retina appeared disrupted. Following transplantation to rdGFAP–/–vim–/– mice, CD44 immunolabeling was absent or disrupted over larger areas in adjacency to the grafts, than in transplantation to control animals (rdGFAP+/+vim+/+). However, this did not correlate with better integration. Conclusions: The results suggest that the outer limiting membrane in rdGFAP–/–vim–/– mice is more susceptible to damage by the transplantation procedure and/or that expression of CD44 is down–regulated in rdGFAP–/–vim–/– retinas in places where the graft and host abut. In any case, the inability to express GFAP and vimentin does not appear to support better integration between fragmented retinal grafts and hosts with photoreceptor degeneration.
Keywords: transplantation • retinal glia • retinal culture