Harnessing Astrocytes and Müller Glial Cells in the Retina for Survival and Regeneration of Retinal Ganglion Cells

Yoo, Hyung-Suk; Shanmugalingam, Ushananthini; Smith, Patrice D.

doi:10.3390/cells10061339

Cited by 25 publications

(25 citation statements)

References 93 publications

(185 reference statements)

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“…These factors include Bdnf, Cntf, and Igf1 (Kermer et al, 2000;Pernet and Polo, 2006;Yungher et al, 2015;Luo et al, 2016). Along this line, several studies have demonstrated that glial cells including Müller cells release growth factors, which can recue RGCs after axonal injury (Yoo et al, 2021). Thus, a question arises as to, albeit temporarily, why some RGCs are protected while others die when these factors are provided?…”

Section: Resistance and Susceptibility Of Retinal Ganglion Cell Subty...mentioning

confidence: 99%

Subtype-specific survival and regeneration of retinal ganglion cells in response to injury

Tapia

Nascimento-dos-Santos

Park

2022

Front. Cell Dev. Biol.

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Retinal ganglion cells (RGCs) are a heterogeneous population of neurons that function synchronously to convey visual information through the optic nerve to retinorecipient target areas in the brain. Injury or disease to the optic nerve results in RGC degeneration and loss of visual function, as few RGCs survive, and even fewer can be provoked to regenerate their axons. Despite causative insults being broadly shared, regeneration studies demonstrate that RGC types exhibit differential resilience to injury and undergo selective survival and regeneration of their axons. While most early studies have identified these RGC types based their morphological and physiological characteristics, recent advances in transgenic and gene sequencing technologies have further enabled type identification based on unique molecular features. In this review, we provide an overview of the well characterized RGC types and identify those shown to preferentially survive and regenerate in various regeneration models. Furthermore, we discuss cellular characteristics of both the resilient and susceptible RGC types including the combinatorial expression of different molecular markers that identify these specific populations. Lastly, we discuss potential molecular mechanisms and genes found to be selectively expressed by specific types that may contribute to their reparative capacity. Together, we describe the studies that lay the important groundwork for identifying factors that promote neural regeneration and help advance the development of targeted therapy for the treatment of RGC degeneration as well as neurodegenerative diseases in general.

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Section: Resistance and Susceptibility Of Retinal Ganglion Cell Subty...mentioning

confidence: 99%

Subtype-specific survival and regeneration of retinal ganglion cells in response to injury

Tapia

Nascimento-dos-Santos

Park

2022

Front. Cell Dev. Biol.

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“…Astrocytes are an integral component of the neurovascular unit, regulating and maintaining the BRB [ 19 , 20 ]. Since we observe a retinal vascular phenotype with age in GC1 −/− mice, we investigated whether astrocytes were morphologically changed.…”

Section: Resultsmentioning

confidence: 99%

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice

Holden

Awamlh

Croteau

et al. 2022

IJMS

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The nitric oxide–guanylyl cyclase-1–cyclic guanylate monophosphate (NO–GC-1–cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1−/−) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1−/− mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1−/− and wild type mice. GC1−/− mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1−/− mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1−/− mice.

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“…The migration of MG has been particularly characterized in response to the upregulation of growth factors such as EGF and VEGF [ 13 , 177 , 197 ]. Concentration gradients of VEGF have demonstrated to increase the chemotactic response of MG in vitro, which correlated to the increased concentration of VEGF in later stages of neovascular retinopathies in vitro (21484851, 24412518).…”

Section: Examining the Neuroprotective Response Of Mgmentioning

confidence: 99%

“…During initial, or short-term, gliosis, MG become reactive by undergoing hypertrophic changes in morphology, radial extension of cellular processes, and proliferation. These reactive behaviors are also accompanied by the upregulation of neurotrophic factors, cytokines and enhanced homeostatic regulation in MG to ensure neuronal survival and communication [ 13 ]. However, prolonged gliotic responses can produce excessive MG proliferation, which displaces adjacent neurons to disrupt synaptic networks, curtail transmission of photonic signaling, and impede retinal regeneration [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Harnessing the Neuroprotective Behaviors of Müller Glia for Retinal Repair

Peña¹,

Vázquez²

2022

Front. Biosci. (Landmark Ed)

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Progressive and irreversible vision loss in mature and aging adults creates a health and economic burden, worldwide. Despite the advancements of many contemporary therapies to restore vision, few approaches have considered the innate benefits of gliosis, the endogenous processes of retinal repair that precede vision loss. Retinal gliosis is fundamentally driven by Müller glia (MG) and is characterized by three primary cellular mechanisms: hypertrophy, proliferation, and migration. In early stages of gliosis, these processes have neuroprotective potential to halt the progression of disease and encourage synaptic activity among neurons. Later stages, however, can lead to glial scarring, which is a hallmark of disease progression and blindness. As a result, the neuroprotective abilities of MG have remained incompletely explored and poorly integrated into current treatment regimens. Bioengineering studies of the intrinsic behaviors of MG hold promise to exploit glial reparative ability, while repressing neuro-disruptive MG responses. In particular, recent in vitro systems have become primary models to analyze individual gliotic processes and provide a stepping stone for in vivo strategies. This review highlights recent studies of MG gliosis seeking to harness MG neuroprotective ability for regeneration using contemporary biotechnologies. We emphasize the importance of studying gliosis as a reparative mechanism, rather than disregarding it as an unfortunate clinical prognosis in diseased retina.

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Harnessing Astrocytes and Müller Glial Cells in the Retina for Survival and Regeneration of Retinal Ganglion Cells

Cited by 25 publications

References 93 publications

Subtype-specific survival and regeneration of retinal ganglion cells in response to injury

Subtype-specific survival and regeneration of retinal ganglion cells in response to injury

Dysfunctional cGMP Signaling Leads to Age-Related Retinal Vascular Alterations and Astrocyte Remodeling in Mice

Harnessing the Neuroprotective Behaviors of Müller Glia for Retinal Repair

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