Autophagy dysregulation and the fate of retinal ganglion cells in glaucomatous optic neuropathy

Russo, Rossella; Nucci, Carlo Alberto; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Morrone, Luigi Antonio

doi:10.1016/bs.pbr.2015.04.009

Cited by 33 publications

(22 citation statements)

References 118 publications

(129 reference statements)

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“…Upregulation of LC3II and accumulation of autophagosomes have been reported in RGCs following exposure to glaucoma-related stimuli, although the time path varies depending on the initial insult 12 . Increased LC3 immunoreactivity has been reported in GCL between 6 and 24 h after ischemia in rats 29 , 30 .…”

Section: Discussionmentioning

confidence: 99%

Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival

et al. 2018

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Autophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal–lysosomal pathway, is fundamental for neuronal homeostasis and its deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic–ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process. Ischemic insult triggered in the retina an acute induction of autophagy that lasted during the first hours of reperfusion. This early upregulation of the autophagic flux limited RGC death, as demonstrated by the increased neuronal loss observed in mice with genetic impairment of basal autophagy owing to heterozygous ablation of the autophagy-positive modulator Ambra1 (Ambra1+/gt). Upregulation of autophagy was exhausted 24 h after the ischemic event and reduced autophagosomal turnover was associated with build up of the autophagic substrate SQSTM-1/p62, decreased ATG12-ATG5 conjugate, ATG4 and BECN1/Beclin1 expression. Animal fasting or subchronic systemic treatment with rapamycin sustained and prolonged autophagy activation and improved RGC survival, providing proof of principle for autophagy induction as a potential therapeutic strategy in retinal neurodegenerative conditions associated with hypoxic/ischemic stresses.

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Section: Discussionmentioning

confidence: 99%

Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival

et al. 2018

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“…Studies have shown that genetic downregulation of autophagy increases RGC death, whereas pharmacological upregulation of autophagy reduces RGC loss [52]. In a mouse model of ONT, autophagy is upregulated, before RGC cell death, and autophagy upregulation by pharmacological agents reduces axotomy-induced RGC loss.…”

Section: Autophagy In Retinal Ganglion Cellsmentioning

confidence: 99%

Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina

Lin

2018

Ophthalmic Res

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Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has shown that autophagy proteins are involved in retinal physiology and pathology and that defective autophagy contributes to retinal degeneration. In retinal diseases, autophagy plays a dual role: promoting retinal cell survival and death. Autophagy at a normal level helps retinal cells defend themselves against harmful stress; however, excessive autophagy results in retinal deterioration. Both synergistic and antagonistic roles of autophagy and apoptosis in the retina have been reported in the literature. In this review, we summarize the roles of autophagy in the development of the retina and retinal diseases. This review highlights the importance of autophagy in retinal diseases, and targeting autophagy may provide a new therapeutic approach for retinal diseases.

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“…Growing evidence supports the involvement of the autophagic process in the pathophysiology of glaucoma and several studies reported a dysregulation, either toward induction or inhibition, of the pathway (recently reviewed in Russo et al, 2013aRusso et al, , 2015b.…”

Section: Endogenous Pro-survival Pathways and Neuroprotectionmentioning

confidence: 99%

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Nucci

Russo

Martucci

et al. 2016

European Journal of Pharmacology

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a b s t r a c tGlaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible connection between glaucomatous damage and cerebrovascular alterations. The mechanisms underlying RGC loss are not yet fully known but alterations of the autophagy machinery have been recently proposed as a potential contributing factor as for Alzheimer's disease.Here we review the current literature on new strategies for neuroprotection in glaucoma, focusing on pharmacologic strategies to minimize RGC damage.

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Autophagy dysregulation and the fate of retinal ganglion cells in glaucomatous optic neuropathy

Cited by 33 publications

References 118 publications

Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival

Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival

Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

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