Rebuilding the Retina: Prospects for Müller Glial-mediated Self-repair

ABSTRACT

Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments available. The use of stem cells to generate new retinal neurons for transplantation purposes has received significant interest in recent years and is beginning to move towards clinical trials. However, such approaches are likely to be most effective for relatively focal areas of repair. An intriguing complementary approach is endogenous self-repair. Retinal cells from the ciliary marginal zone (CMZ), retinal pigment epithelium (RPE) and Müller glial cells (MG) have all been shown to play a role in retinal repair, typically in lower vertebrates. Among them, MG have received renewed interest, due to their distribution throughout (centre to periphery) the neural retina and their potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons. Triggering these innate self-repair mechanisms represents an exciting therapeutic option in treating retinal degeneration. However, these cells behave differently in mammalian and non-mammalian species, with a considerably restricted potential in mammals. In this short review, we look at some of the recent progress made in our understanding of the signalling pathways that underlie MG-mediated regeneration in lower vertebrates, and some of the challenges that have been revealed in our attempts to reactivate this process in the mammalian retina.

KEYWORDS:

• Müller glia
• regeneration
• stem cells
• neurogenesis
• endogenous repair
• retinal degeneration
• photoreceptors

Disclosure statement

The authors declare no competing interests.

Author Contributions

RL carried out the literature review research, designed the figures and wrote the first draft of the manuscript. RAP contributed to the writing of the manuscript and approved the final version.

Additional information

Funding

This review was supported by grants from the Royal Society [Newton International Fellowship, awarded to R.L.; Grant award number NF171142] and the National Eye Research Centre, UK [grant award number SAC 042].