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K. B. Mallya, M. Antony, S. Balasubramanian, I. Ahmad; Photoreceptor Potential of Human and Rat Muller Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3545.
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We have recently demonstrated that the Muller cells in the mammalian retina are latent neural stem cells (Das et al., 2006, Dev. Biol. 299:283). To determine the relevancy of the stem cell nature of Muller cells in treating retinal degenerations in age-related macular degeneration (AMD) and retinitis pigmentosa(RP) we have begun the comparison of stem cell properties and photoreceptor potential of rat Muller cells and human Muller cell line, HMCL-1 (Lupien and Salesse, 2007, IOVS 48:874).
Enriched rat Muller (rat) and HMCL-1 (human) cells were cultured in the presence of EGF+FGF2 to generate neurospheres. Resulting neurospheres were examined for the expression of neural and retinal progenitor markers. To examine their differentiation potential, neurospheres were cultured in the presence of FBS/retinal cells. Neurospheres were examined for the expression of pan neural and photoreceptor-specific markers. To determine their potential to differentiate into photoreceptors, cells from rat and human Muller cell derived neurospheres were transplanted in the retina of normal rats or those carrying retinal degeneration (S334ter rats).
A subset of both rat and human Muller cells generated neurospheres in the presence of growth factors. However, the frequency of neurosphere formation was greater in the former than latter, which showed strong substratum-preference. The generation of neurospheres by human cells was delayed in comparison to those by rat cells. Cells in rat and human neurospheres were proliferative and expressed neural and retinal progenitor markers. Cells in rat neurospheres, when co-cultured with embryonic (early histogenesis) and neonatal (late histogenesis), differentiated into cells expressing immunoreactivities corresponding to cones (e.g. S opsin) and rods (e.g., rhodopsin), respectively. Cells from rat neurospheres upon transplantation integrated into host retina and those in the outer nuclear layer expressed rhodopsin.
Both rat Muller and HMCL-1 cells display stem cell properties in the presence of growth factors and the former show potential for photoreceptor differentiation. A comparison of photoreceptor potential of species-specific Muller cells will be presented.
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