From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma.

From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma. Ageing Res Rev. 2016 May 27; Authors: Saccà SC, Gandolfi S, Bagnis A, Manni G, Damonte G, Traverso CE, Izzotti A Abstract Glaucoma is a degenerative disease of the eye. Both the anterior and posterior segments of the eye are affected, extensive damage being detectable in the trabecular meshwork and the inner retina-central visual pathway complex. Oxidative stress is claimed to be mainly responsible for molecular damage in the anterior chamber. Indeed, oxidation harms the trabecular meshwork, leading eventually to endothelial cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility and (ultimately) increased IOP. Moreover, free radicals are involved in aging and can be produced in the brain (as well as in the eye) as a result of ischemia, leading to oxidation of the surrounding neurons. Glaucoma-related cell death occurs by means of apoptosis, and apoptosis is triggered by oxidative stress via (a) mitochondrial damage, (b) inflammation, (c) endothelial dysregulation and dysfunction, and (d) hypoxia. The proteomics of the aqueous humor is significantly altered in glaucoma as a result of oxidation-induced trabecular damage. Those proteins whose aqueous humor levels are increased in glaucoma are biomarkers of trabecular meshwork impairment. Their diffusion from the ant...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research

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AbstractGlaucoma is a blindness-causing disease that involves selective damage to retinal ganglion cells (RGCs) and their axons. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system functions, such as pupillary light reflex and circadian rhythms. We analyzed the effect of melatonin on the non-image-forming visual system alterations induced by experimental glaucoma. For this purpose, maleWistar rats were weekly injected with vehicle or chondroitin sulfate into the eye anterior chamber. The non-image-forming visual system was analyzed in terms of (1) melanopsin-expressing RGC numb...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
J Ophthalmol. 2021 Apr 15;2021:4581909. doi: 10.1155/2021/4581909. eCollection 2021.ABSTRACTThe exact mechanism of retinal ganglion cell loss in the pathogenesis of glaucoma is yet to be understood. Mitochondrial damage-associated molecular patterns (DAMPs) resulting from mitochondrial dysfunction have been linked to Leber's hereditary optic neuropathy and autosomal dominant optic atrophy, as well as to brain neurodegenerative diseases. Recent evidence shows that, in conditions where mitochondria are damaged, a sustained inflammatory response and downstream pathological inflammation may ensue. Mitochondrial damage has been...
Source: Journal of Ophthalmology - Category: Opthalmology Authors: Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ai Man Inherited optic neuropathies, including Leber Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), are monogenetic diseases with a final common pathway of mitochondrial dysfunction leading to retinal ganglion cell (RGC) death and ultimately loss of vision. They are, therefore, excellent models with which to investigate this ubiquitous disease process—implicated in both common polygenetic ocular diseases (e.g., Glaucoma) and late-onset central nervous system neurodegenerative diseases (e.g., Parkinson disease). In recent years, cellular and animal models of LHON and DOA have matured in p...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
In conclusion, our study demonstrated that the molecular processes of aging are relatively subtle in their progress, and the aging process of every tissue depends on the tissue's specialized function and environment. Hence, individual gene or process alone cannot be described as the key of aging in the whole organism. Mouse Age Matters: How Age Affects the Murine Plasma Metabolome A large part of metabolomics research relies on experiments involving mouse models, which are usually 6 to 20 weeks of age. However, in this age range mice undergo dramatic developmental changes. Even small age differences may l...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, except for the reduction in body weight, the aging characteristics related to epidermal and muscle tissue in mice were significantly ameliorated in the CR group compared with the control group. Additional studies have indicated that not stem cells themselves but the stem cell microenvironment is the key factor mediating stem cell activation, proliferation and differentiation. Mitochondrial dysfunction is an important factor leading to age-related muscular atrophy. Considering the dependence of skeletal muscle on ATP, loss of mitochondrial function, which can lead to a decrease in strength and enduranc...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Several research groups and companies are working on in vivo applications of cellular reprogramming. Today's research materials cover recent work from David Sinclair's team showing off the use of reprogramming to produce regeneration of damaged nervous system tissue in the eye and optic nerve. Glaucoma is a condition in which rising pressure in the eyeball progressively harms the retina and optic nerve. Since nerve tissue doesn't regenerate well in mammals, loss of vision is irreversible. This is one of many conditions for which the ability to regenerate nerve tissue would be a great benefit. Since its discovery, re...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
This study was designed to investigate the role of PR-619 in regulating mitophagy of RGCs under glutamate excitotoxicity. Primary cultured RGCs were incubated with PR-619 or vehicle control in the excitotoxicity model of 100 µM glutamate treatment. Mitochondrial membrane potential was assessed by JC-1 assay. Cytotoxicity of RGCs was measured by LDH activity. Proteins levels of parkin, optineurin, LAMP1, Bax, Bcl-2 and the LC3-II/I ratio were analyzed by western blot. The distribution and morphology of mitochondria in RGCs was stained by MitoTracker and antibody against mitochondria membrane protein, and examined by c...
Source: NeuroReport - Category: Neurology Tags: Degeneration and Repair Source Type: research
Abstract Research demonstrates that senescence is associated with tissue and organ dysfunction, and the eye is no exception. Sequelae arising from aging have been well-defined as distinct clinical entities and vision-impairment has significant psychosocial consequences. Retina and adjacent tissues like retinal pigmented epithelium (RPE) and choroid are the key structures that are required for visual perception. Any structural and functional changes in retinal layers and blood retinal barrier (BRB) could lead to age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. Further, there are sign...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research
Abstract Improving cellular access to energy substrates is one strategy to overcome observed declines in energy production and utilization in the aged and pathologic central nervous system. Monocarboxylate transporters (MCTs), the movers of lactate, pyruvate, and ketone bodies into or out of a cell, are significantly decreased in the DBA/2 J mouse model of glaucoma. In order to confirm MCT decreases are disease-associated, we decreased MCT2 in the retinas of MCT2fl/+ mice using an injection of AAV2-cre, observing significant decline in ATP production and visual evoked potential. Restoring MCT2 levels in retinal ...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
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