Retinal transplantation of neural progenitor cells in the rhodopsin transgenic
rat
Derek B. Lauritzen, M.D.1,2, Yasuo Kurimoto,
M.D.,
Michael Young, Ph.D. (USA- Boston, MA)
¹Massachusetts Eye and Ear Infirmary, ²Retina Specialists
of Boston, Schepens Eye Research Institute (all authors), and the Harvard
Medical School (all authors)
Neural
cells derived from the adult rat brain para-hippocamal region have been
shown to be self-renewing and multipotential (neural progenitor or stem
cells). We have shown that these cells survive, integrate, and differentiate
when transplanted into a Royal College of Surgeons (RCS) rat model of
retinal degeneration. A model in which, despite the differentiation of
these brain neural progenitor cells as determined by morphology and immunohistochemistry,
there has been no evidence of photoreceptor differentiation. The recent
development of two lines of transgenic mutant rhodopsin rats (pro23his
and ser334term) has provided rat models of retinal degeneration in which
the defect is localized to the photoreceptor. Brain neural progenitor
cells transplanted to the intravitreal and subretinal space of the pro23his
and ser334t mutant rats show survival, integration, and limited differentiation.
We have found only limited evidence of photoreceptor differentiation with
transplantation of adult neural progenitor cells and hypothesize that
these cells possess a certain level of differentiation precluding their
differentiation into photoreceptors. Further studies utilizing neural
progenitor cells transplanted into the developing retina have shown success
in producing cells which survive, integrate, and differentiate into cells
expressing recoverin, suggesting that transplanted stem cells may have
the capacity to respond to signals present during differentiation and
degeneration in the CNS. We are presently investigating the nature of
the cues in the developing, as well as the mature diseased retinal microenvironment.
Supported in part by the Minda de Gunzburg Center for Retinal Transplantation and NEI Grant 09595.