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C. Abburi, A. Anand, I. Ahmad; Characterization of Ciliary Epithelium Stem Cell Niche. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3546. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The adult ciliary epithelium (CE) harbors neural stem cells. These stem cells are activated in response to growth factors both in vitro and in vivo. They display properties and potential similar to that possessed by retinal stem cells/progenitors. They express retinal progenitor markers and, given conducive conditions, can differentiate along photoreceptor and RGC sub-lineages (Das et al., 2005, Vis. Res. 45:1656). These cells are valid target for regenerative therapy for retinal degeneration encountered in diseases such as age-related macular degeneration (AMD). To facilitate this approach we are examining the regulation of CE stem cells in the context of their environment.
Sections from adult rat eyes, treated with PBS or growth factors (Zhao et al., 2005, Dev. Dyn. 232:249), were subjected to immunohistochemical analysis to localize immunoreactivities corresponding to factors characterizing the stem cell niche (e.g., Notch1, Delta1/Jagged1, c-Kit, cadherins, Ang4, Tie2) in the CE. CE stem cells were cultured in conditions of perturbed Notch/Wnt/Shh/c-kit signaling to determine the effects of defined factors on cell proliferation, self-renewal and differentiation. CE stem cells were co-cultured in the presence of different CE cells/retinal cells/hematopoietic cells in the presence and absence of perturbed Notch/Wnt/c-kit signaling to examine the effects of different environments (and underlying mechanisms) on stem cell properties and potential.
CE exposed to growth factors contained proliferating (BrdU+ and ki67+) cells that expressed Chx10 and Pax6. Immunoreactivities for Notch1 and c-Kit were detected in the region corresponding to pigmented portion of the CE. Immunoreactivities corresponding to Ang4, one of the angiopoietin family of growth factors, were detected on the outer surface of the CE. Its receptor, Tie2, was not detected in initial experiments. The ability of CE stem cells to generate neurospheres was profoundly affected by Notch, Wnt and c-kit pathways. Attenuation of any of these pathways by drugs (DAPT), antagonists (FzdCRD) or antibodies (anti-c-Kit antibody) led to a significant decrease in the number of neurospheres generated.
The CE express markers corresponding to those that characterize stem cell niche and therefore, offers an environment conducive for the maintenance of stem cells. Some of the pathways active in the niche may belong to Notch, Wnt and c-kit signaling.
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