ABSTRACT
@#Zebrafish has become a popular model for the study of ocular degenerative diseases due to its similarity with human visual system and its great potential of retinal regeneration. The degenerative diseases, especially retinal degeneration and optic nerve degeneration, can seriously affect visual acuity, also the regeneration and repair are very limited, which can lead to blindness in severe cases. In contrast to mammals, zebrafish can repair optic nerve axon damage and stimulate retinal Müller glial cells to differentiate into multifunctional progenitor cells, thereby, regenerating retinal neurons and nerve axons and restoring normal visual function. This review focuses on the application of zebrafish model in eye diseases and the key signaling pathways of zebrafish retinal neurons and Müller glial cells to initiate regeneration and repair in response to injury.
ABSTRACT
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.