Research progress and problems of endogenous neural stem cell properties of retinal Müller cells

Retinal degeneration is an incurable and irreversible blinding disease caused by the retinal neural cell death.An effective and safe strategy to substitute these injured cells is necessary for retinal recovery.Neural stem cells (NSCs) can differentiate into neural and glial cells.While Müller cells, the main endogenous NSCs in retina, have the features to reentry into the cell cycle and differentiate into neural cells after retinal damage.Although it is highly effective for retinal Müller cell differentiation spontaneously after retinal injury in vertebrates, this feature is rigorously restricted in mammals.Recently, some transcription factors, such as Ascl1, sox2, lin28 and atoh7, can drive quiescent Müller cells back into proliferation to generate new retinal neurons.Moreover, combining Ascl1 expression with a histone deacetylase inhibitor can bypass the limitation and increase the generation of new neurons in adult retina.These regenerated neurons integrate the existing neuronal network and are able to respond to light, indicating that they can likely be used to restore vision.In addition, transplantation of exogenous stem cells can induce Müller cell reprogramming.While these results are extremely promising, the regenerative response is still limited, likely because the proliferative capacity of mammalian Müller cells is low in comparison to their zebrafish counterparts.There may be some kinds of unclear reverse mechanism that suppresses the reprogramming of Müller cells.It is indeed necessary to identify new factors increasing the efficiency of regenerative response.