Abstract
Glaucoma, the second leading cause of blindness worldwide, is an incurable neurodegenerative disorder due to the dysfunction of retinal ganglion cells (RGCs). RGCs function as the only output neurons conveying the detected light information from the retina to the brain, which is a bottleneck of vision formation. RGCs in mammals cannot regenerate if injured, and RGC subtypes differ dramatically in their ability to survive and regenerate after injury. Recently, novel RGC subtypes and markers have been uncovered in succession. Meanwhile, apart from great advances in RGC axon regeneration, some degree of experimental RGC regeneration has been achieved by the in vitro differentiation of embryonic stem cells and induced pluripotent stem cells or in vivo somatic cell reprogramming, which provides insights into the future therapy of myriad neurodegenerative disorders. Further approaches to the combination of different factors will be necessary to develop efficacious future therapeutic strategies to promote ultimate axon and RGC regeneration and functional vision recovery following injury.
Highlights
Glaucoma is the second leading cause of blindness worldwide, which affects about79.6 million people by 2020 [1]
The present review addresses recent advancements in this field of retinal ganglion cells (RGCs) and axon regeneration including (i) factors that affect axon regeneration; (ii) the differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) into cells with specific RGC characteristics; and (iii) the regeneration of RGCs by reprogramming
Forced expression of melanopsin in the RGCs induced axonal regeneration after optic nerve crush (ONC) by activation of the mTOR signaling pathway, which was comparable to PTEN knockdown
Summary
Glaucoma is the second leading cause of blindness worldwide, which affects about. 79.6 million people by 2020 [1]. Glaucoma is an incurable neurodegenerative disorder marked by selective, progressive, and irreversible degeneration of retinal ganglion cells (RGCs) and the optic nerve [2]. The death or dysfunction of RGCs causes irreversible blindness because surviving RGCs lose the intrinsic capacity to regenerate themselves and their axons, similar to most neurons in the mammalian mature central nervous system (CNS) [8]. Therapeutic strategies that support visual restoration have focused on protecting RGCs from degeneration, promoting RGC and axon regeneration after injury, and reestablishing their correct projection relationships. In the past few years, numerous studies have focused on promoting the regeneration of RGCs and their axons and have made great progress. Researchers have identified many factors that suppress or promote RGC survival and optic nerve regeneration. The present review addresses recent advancements in this field of RGC and axon regeneration including (i) factors that affect axon regeneration; (ii) the differentiation of embryonic stem cells (ESCs) and iPSCs into cells with specific RGC characteristics; and (iii) the regeneration of RGCs by reprogramming
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