Abstract
Purpose: :
We previously demonstrated that treatment of gliotoxin was useful for the integration of retinal transplanted cells (T. Masumi et al., ARVO 2004, #5179). To determine whether treatment of gliotoxin leads to successful replacement of photoreceptor cells following retinal transplantation in Transducin knockout mice, which are photoreceptor dysfunctional model.
Methods: :
To promote grafted cell integration, Transducin knockout mice received gliotoxin subretinal injection 2 days before transplantation. Donor retinal cells were isolated from neonatal (P0–2) mice carrying enhanced green fluorescent protein transgene (EGFP). The donor cells were transplanted into adult Transducin knockout mice by subretinal injection. Morphologies of grafted cells were examined at 14d, 21d and 1M after transplantation in retinal cross section. To determine the cellular identity of grafted cells, we performed immunohistochemistry for photoreceptor markers, Recoverin and Nr2e3.
Results: :
EGFP–positive cells integrated into the host retina of Transducin knockout mice and extended neurites. Many integrated cells of host retina migrated to the outer nuclear layer (ONL) and exhibited typical morphology of photoreceptor cells–with cell body localized in the ONL and extended outer segment–like structure into the outer segment layer. Most of these cells were also expressed with photoreceptor markers, Recoverin and Nr2e3.
Conclusions: :
Our results revealed that transplanted retinal cells could integrate and differentiate into photoreceptors in the photoreceptor dysfunctional host with gliotoxin treatment. Treatment of gliotoxin to the host may be a prerequisite for the success of retinal transplantation therapy.
Keywords: transplantation • photoreceptors • differentiation