bFGF and insulin lead to migration of Muller glia to photoreceptor layer in rd1 mouse retina

摘要

Muller glia can act as endogenous stem cells and regenerate the missing neurons in the injured or degenerating retina in lower vertebrates. However, mammalian Muller glia, although can sometimes express stem cell markers and specific neuronal proteins in response to injury or degeneration, do not differentiate into functional neurons. We asked whether bFGF and insulin would stimulate the Muller glia to migrate, proliferate and differentiate into photoreceptors in rd1 mouse. We administered single or repeated (two or three) intravitreal injections of basic fibroblast growth factor (bFGF;200 mu g) and insulin (2 mu g) in 2-week-old rd1 mice. Muller glia were checked for proliferation, migration and differentiation using immunostaining. A single injection resulted within 5 days in a decrease in the numbers of Muller glia in the inner nuclear layer (INL) and a corresponding increase in the outer nuclear layer (ONL). The total number of Muller glia in the INL and ONL was unaltered, suggesting that they did not proliferate, but migrated from INL to ONL. However, maintaining the Muller cells in the ONL for two weeks or longer required repeated injections of bFGF and insulin. Interestingly, all Muller cells in the ONL expressed chx10, a stem cell marker. We did not find any immunolabeling for rhodopsin, m-opsin or s-opsin in the Muller glia in the ONL.