Insights on the Regeneration Potential of Müller Glia in the Mammalian Retina

Abstract

Müller glia, the major glial cell types in the retina, maintain retinal homeostasis and provide structural support to retinal photoreceptors. They also possess regenerative potential that might be used for retinal repair in response to injury or disease. In teleost fish (such as zebrafish), the Müller glia response to injury involves reprogramming events that result in a population of proliferative neural progenitors that can regenerate the injured retina. Recent studies have revealed several important mechanisms for the regenerative capacity of Müller glia in fish, which may shed more light on the mechanisms of Müller glia reprogramming and regeneration in mammals. Mammalian Müller glia can adopt stem cell characteristics, and in response to special conditions, be persuaded to proliferate and regenerate, although their native regeneration potential is limited. In this review, we consider the work to date revealing the regenerative potential of the mammalian Müller glia and discuss whether they are a potential source for cell regeneration therapy in humans.

Visual Function is Gradually Restored During Retina Regeneration in Adult Zebrafish

“…Available treatments and therapies are very limited allowing in most cases only a deferral of the underlying etiopathology. Various attempts have been made to prevent or restore vision loss using prosthetic devices, gene therapy, optogenetics as well as cell transplantations (Salman et al, 2021). Another promising approach aims to rekindle the innate property of the retina to selfrepair which has been observed in several vertebrate species.…”

“…Müller glia, the retinal stem cells, remain either quiescent or respond to injury with reactive gliosis (Karl and Reh, 2010). Several successful attempts have been recently made enabling mammalian Müller glia to evade quiescence and stimulating a regenerative response to ameliorate the etiopathology (reviewed in (Salman et al, 2021)). However, Müller glia-based regeneration is still insufficient in mammals.…”

CRISPR/Cas9-Mediated Models of Retinitis Pigmentosa Reveal Differential Proliferative Response of Müller Cells between Xenopus laevis and Xenopus tropicalis

“…In this species, mechanical injury or conditional rod cell ablation triggers Müller cells to re-enter into the cell cycle and regenerate lost photoreceptors. Despite the absence of spontaneous regeneration in mammals, in vitro and in vivo studies demonstrated that mammalian Müller cells can also reprogram and produce new neurons in response to injury, provided treatment with appropriate growth factors or following overexpression of specific proneural genes [ 4 , 5 , 6 , 7 ]. Although much progress has been made these past few years in identifying genes and signalling pathways sustaining Müller cell regeneration [ 5 , 6 ], the molecular bases that account for interspecies differential potential are still largely unknown.…”

Beyond Genetics: The Role of Metabolism in Photoreceptor Survival, Development and Repair

“…Müller glia also play a key role in the production of neurotransmitter precursors, catalyzing the conversion of glutamate to glutamine by glutamine synthetase, which is then used by photoreceptors to remake glutamate as neurotransmitter to relay signals to bipolar cells ( Pow and Crook, 1996 ). Müller cells also recycle glutamate and GABA neurotransmitters, and are well positioned to carry out these functions as they extend processes in the plexiform layers that ensheathe neuronal synapses ( Salman et al, 2021 ).…”