Age-related accumulation of phosphorylated mitofusin 2 protein in retinal ganglion cells correlates with glaucoma progression.

We examined the correlation between bioenergetics and axonal transport with mitochondrial mutation frequency and post-translational modifications of mitofusin 2 (Mfn2) in RGCs during glaucoma progression. No increase in the frequency of mtDNA mutations was detected, but we observed significant shifts in mitochondrial protein species. Mfn2 is a fusion protein that functions in mitochondrial biogenesis, maintenance, and mitochondrial transport. We demonstrate that Mfn2 accumulates selectively in RGCs during glaucomatous degeneration, that two novel states of Mfn2 exist in retina and ON, and identify a phosphorylated form that selectively accumulates in RGCs, but is absent in ON. Phosphorylation of Mfn2 is correlated with higher ubiquitination, and failure of the protein to reach the ON. Together, these data suggest that post-translational modification of Mfn2 is associated with its dysregulation during a window of metabolic vulnerability that precedes glaucomatous degeneration. Future work to either manipulate expression of Mfn2 or to prevent its degradation could have therapeutic value in the treatment of neurodegenerative diseases where long-tract axons are vulnerable. PMID: 28684211 [PubMed - as supplied by publisher]
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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In conclusion, with study of the frailty syndrome still in its infancy, frailty analysis remains a major challenge. It is a challenge that needs to be overcome in order to shed light on the multiple mechanisms involved in the pathogenesis of this syndrome. Although several mechanisms contribute to frailty, immune system alteration seems to play a central role: this syndrome is characterized by increased levels of pro-inflammatory markers and the resulting pro-inflammatory status can have negative effects on various organs. Future studies should aim to better clarify the immune system alteration in frailty, and seek to esta...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 23 June 2019Source: Progress in Retinal and Eye ResearchAuthor(s): Muneeb A. Faiq, Gadi Wollstein, Joel S. Schuman, Kevin C. ChanAbstractThe cholinergic system has a crucial role to play in visual function. Although cholinergic drugs have been a focus of attention as glaucoma medications for reducing eye pressure, little is known about the potential modality for neuronal survival and/or enhancement in visual impairments. Citicoline, a naturally occurring compound and FDA approved dietary supplement, is a nootropic agent that is recently demonstrated to be effective in ameliorating ischemi...
Source: Progress in Retinal and Eye Research - Category: Opthalmology Source Type: research
Authors: Esquiva G, Hannibal J Abstract Melanopsin-expressing retinal ganglion cells (mRGCs) constitute a system in the mammalian retina used for irradiance detection, regulating non-image forming functions, such as photoentrainment of circadian rhythms, control of the pupillary light reflex, masking response, light-regulated melatonin secretion, and modulation of the sleep/wake cycle. There are five subtypes of mRGCs differentiated by morphology and function. Recent years of research on mRGCs have identified a broad number of neurodegenerative diseases in the eye and the brain with altered physiologic light respon...
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research
Conclusions: These results suggest that Stc1 may be a downstream candidate of Gpnmb, and that both genes interact with other genes in a network to develop glaucoma pathogenesis through mechanisms such as apoptosis and oxidative stress. PMID: 31057322 [PubMed - in process]
Source: Molecular Vision - Category: Molecular Biology Tags: Mol Vis Source Type: research
In this study, we found that senescent chondrocytes isolated from OA patients secrete more EVs compared with nonsenescent chondrocytes. These EVs inhibit cartilage ECM deposition by healthy chondrocytes and can induce a senescent state in nearby cells. We profiled the miR and protein content of EVs isolated from the synovial fluid of OA joints from mice with SnCs. After treatment with a molecule to remove SnCs, termed a senolytic, the composition of EV-associated miR and protein was markedly altered. The senolytic reduced OA development and enhanced chondrogenesis, and these were attributable to several specific differenti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 11 April 2019Source: Redox BiologyAuthor(s): Soumya Navneet, Jing Zhao, Jing Wang, Barbara Mysona, Shannon Barwick, Navneet Ammal Kaidery, Alan Saul, Ismail Kaddour-Djebbar, Wendy B. Bollag, Bobby Thomas, Kathryn E. Bollinger, Sylvia B. SmithAbstractHyperhomocysteinemia (Hhcy), or increased levels of the excitatory amino acid homocysteine (Hcy), is implicated in glaucoma, a disease characterized by increased oxidative stress and loss of retinal ganglion cells (RGCs). Whether Hhcy is causative or merely a biomarker for RGC loss in glaucoma is unknown. Here we analyzed the role of NRF2, a m...
Source: Redox Biology - Category: Biology Source Type: research
Light-Induced Pupillary Responses in Alzheimer's Disease Pratik S. Chougule1, Raymond P. Najjar1,2, Maxwell T. Finkelstein1, Nagaendran Kandiah3,4 and Dan Milea1,2,5* 1Department of Visual Neurosciences, Singapore Eye Research Institute, Singapore, Singapore 2The Ophthalmology &Visual Sciences ACP, Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore 3Department of Neurology, National Neuroscience Institute, Singapore, Singapore 4Duke-National University of Singapore (NUS), Singapore, Singapore 5Singapore National Eye Centre, Singapore, Singapore The impact of Alzheimer&...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Publication date: Available online 27 February 2019Source: Neurochemistry InternationalAuthor(s): C. Núñez-Álvarez, N.N. OsborneAbstractNeurones are dependent on their mitochondria to produce the necessary amounts of ATP for survival. Retinal ganglion cells (RGCs) have a particularly large number of mitochondria which—unlike neurones in the brain—are exposed to visual light of 400–850 nm. Here we demonstrate that short wavelength visual blue light negatively affects mitochondrial function, causing oxidative stress and decreased cell survival. In contrast, long wavelength red light e...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract The benefits of physical exercise on health and well‐being have been studied in a wide range of systemic and ocular diseases, including glaucoma, a progressive optic neuropathy characterized by accelerated apoptosis of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) and insufficient ocular perfusion have been postulated to be the two main theories in glaucoma development and progression. The effects of exercise in these two aspects have been demonstrated by numerous researches. A review in 2009 focusing on these two theories concluded that exercise results in transient IOP reduction but an inc...
Source: Acta Ophthalmologica - Category: Opthalmology Authors: Tags: Review Article Source Type: research
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