Targeting the NLRP3 Inflammasome in Glaucoma.
Sophie Coyle,Mohammed Naeem Khan,Melody Chemaly,Breedge Callaghan,Chelsey Doyle,Colin E. Willoughby,Sarah D. Atkinson,Meredith S Gregory-Ksander,Victoria McGilligan +8 more
- Vol. 11, Iss: 8, pp 1239
TLDR
In this article, the NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma, which results in IL-1β processing, resulting in axon degeneration and the death of retinal ganglion cells (RGCs).Abstract:
Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30-40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented.read more
Citations
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Neuroprotection for Age-Related Macular Degeneration
TL;DR: Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with Geographic Atrophy (GA), including reduction of oxidative stress, modulation of visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue-derived cells, and RPE replacement as discussed by the authors .
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Glaucomatous optic neuropathy: Mitochondrial dynamics, dysfunction and protection in retinal ganglion cells
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