Protect, Repair, and Regenerate: Towards Restoring Vision in Glaucoma

Wareham, Lauren K.; Risner, Michael L.; Calkins, David J.

doi:10.1007/s40135-020-00259-5

Cited by 25 publications

(24 citation statements)

References 122 publications

(128 reference statements)

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“…Instead, the only available treatments are indirectly protective for RGCs by lowering the intraocular pressure (IOP). It is, therefore, crucial to identify cellular mechanisms for the prevention of RGC degeneration, the repair of dysfunctional cells, and the promotion of axonal regeneration to limit the projected burden of vision impairment and blindness from glaucoma ( 9 , 10 ). Although the most investigated risk factors for glaucoma progression include IOP, age, genetic background, thinner corneal thickness, and vascular dysregulation ( 11 ), other disease mechanisms such as oxidative stress, mitochondrial dysfunction, excitotoxicity, and immunological processes may contribute to the pathophysiology of the disease ( 2 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

et al. 2021

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Glaucoma is the second leading cause of blindness worldwide, affecting ~80 million people by 2020 (1, 2). The condition is characterized by a progressive loss of retinal ganglion cells (RGCs) and their axons accompanied by visual field loss. The underlying pathophysiology of glaucoma remains elusive. Glaucoma is recognized as a multifactorial disease, and lowering intraocular pressure (IOP) is the only treatment that has been shown to slow the progression of the condition. However, a significant number of glaucoma patients continue to go blind despite intraocular pressure-lowering treatment (2). Thus, the need for alternative treatment strategies is indisputable. Accumulating evidence suggests that glial cells play a significant role in supporting RGC function and that glial dysfunction may contribute to optic nerve disease. Here, we review recent advances in understanding the role of glial cells in the pathophysiology of glaucoma. A particular focus is on the dynamic and essential interactions between glial cells and RGCs and potential therapeutic approaches to glaucoma by targeting glial cells.

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Section: Introductionmentioning

confidence: 99%

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

et al. 2021

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“…However, regardless of hypotensive therapeutic intervention, many patients continue to lose vision [ 9 ]. Thus, like age-related diseases of the brain itself, therapeutics are needed that address neurodegeneration directly [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by WldS depends on retinal ganglion cell type and age in glaucoma

Risner

Pasini

McGrady

et al. 2021

Mol Neurodegeneration

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Background Early challenges to axonal physiology, active transport, and ultrastructure are endemic to age-related neurodegenerative disorders, including those affecting the optic nerve. Chief among these, glaucoma causes irreversible vision loss through sensitivity to intraocular pressure (IOP) that challenges retinal ganglion cell (RGC) axons, which comprise the optic nerve. Early RGC axonopathy includes distal to proximal progression that implicates a slow form of Wallerian degeneration. In multiple disease models, including inducible glaucoma, expression of the slow Wallerian degeneration (WldS) allele slows axon degeneration and confers protection to cell bodies. Methods Using an inducible model of glaucoma along with whole-cell patch clamp electrophysiology and morphological analysis, we tested if WldS also protects RGC light responses and dendrites and, if so, whether this protection depends upon RGC type. We induced glaucoma in young and aged mice to determine if neuroprotection by WldS on anterograde axonal transport and spatial contrast acuity depends on age. Results We found WldS protects dendritic morphology and light-evoked responses of RGCs that signal light onset (αON-Sustained) during IOP elevation. However, IOP elevation significantly reduces dendritic complexity and light responses of RGCs that respond to light offset (αOFF-Sustained) regardless of WldS. As expected, WldS preserves anterograde axon transport and spatial acuity in young adult mice, but its protection is significantly limited in aged mice. Conclusion The efficacy of WldS in conferring protection to neurons and their axons varies by cell type and diminishes with age.

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“…Herausforderungen stellen sich sowohl bei der Definition des anpassbaren Einbringungsweges für einen effektiven retinalen Organoidtransfer in die Empfänger-Retina als auch bei der Frage, wie die Injektion körperfremder Zellen die native Netzhautumgebung beeinflusst und ob Spender-RGC sich integrieren und funktionelle Schaltkreise bilden, die die visuelle Verarbeitung wiederherstellen. Um die Sehfunktion wiederherzustellen, müssen die transplantierten RGC Axone wachsen lassen, die über den Sehnervenkopf hinausreichen; weitere Erfordernisse sind die Remyelinisierung durch Oligodendrozyten und die korrekte Führung zu Anschlussstellen im Gehirn, wo neue synaptische Verbindungen gebildet werden können kann [391]. Wenn es gelingt, diese Hürden zu überwinden, könnten aus Stammzellen gewonnene RGC oder RGC-Vorläufer zu einer praktischen und bevorzugten Strategie für die Behandlung von Patienten mit Glaukom werden.…”

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Neuartige Wirkstoffabgabesysteme für die Glaukomtherapie: Hürden und Lösungsansätze für die Formulierung

et al. 2021

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Das Glaukom gilt als eins der größten gesundheitlichen Probleme weltweit. Es ist die häufigste vermeidbare Erblindungsursache – zum Einen, weil es in der Frühphase asymptomatisch bleibt, zum Anderen wegen mangelnder Therapietreue der Patienten. Es gibt bei der Behandlung des Glaukoms verschiedene Herangehensweisen, die jeweils auf den Einzelfall abgestimmt werden müssen. Die erste Therapielinie ist eine medikamentöse Behandlung. Da jedoch die herkömmlichen Darreichungsformen zahlreiche Nachteile aufweisen, wird intensiv an der Entwicklung neuartiger Wirkstoffabgabesysteme für die Glaukomtherapie gearbeitet. Die vorliegende Übersichtsarbeit gibt einen Überblick über Lösungsansätze und Strategien bei der Entwicklung von Darreichungsformen wie in situ gelierenden Systemen, Nanosystemen, okulären Inserten, Kontaktlinsen, Cornea Shields aus Kollagen, okulären Implantaten, Mikronadeln und Iontophoresesystemen. Ergänzend werden Ergebnisse von Studien zur Wirksamkeit dieser Wirkstoffabgabesysteme kurz vorgestellt.

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Protect, Repair, and Regenerate: Towards Restoring Vision in Glaucoma

Cited by 25 publications

References 122 publications

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

Neuroprotection by WldS depends on retinal ganglion cell type and age in glaucoma

Neuartige Wirkstoffabgabesysteme für die Glaukomtherapie: Hürden und Lösungsansätze für die Formulierung

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