title: From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma.
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 anterior to the posterior segment of the eye may be relevant in the cascade of events triggering apoptosis in the inner retinal layers, including the ganglion cells.
authors.affiliation: IRCCS San Martino University Hospital, Department of Neuroscience and Sense Organs, San Martino Hospital, Ophthalmology Unit, Viale Benedetto XV, 16132 Genoa, Italy. Electronic address: sergio.sacca@hsanmartino.it.
authors.forename: Sergio Claudio
authors.initials: SC
authors.lastname: Saccà
authors.affiliation: Ophthalmology Unit, Department of Biological, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gandolfi
authors.affiliation: University of Genoa, Eye Clinic, Department of Neuroscience and Sense Organs, Viale Benedetto XV, 5, 16148 Genoa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bagnis
authors.affiliation: Dept. of Clinical Science and Translational Medicine, University Tor Vergata, Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Manni
authors.affiliation: Dept. of Experimental Medicine, Section of Biochemistry and Center of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Damonte
authors.affiliation: University of Genoa, Eye Clinic, Department of Neuroscience and Sense Organs, Viale Benedetto XV, 5, 16148 Genoa, Italy.
authors.forename: Carlo Enrico
authors.initials: CE
authors.lastname: Traverso
authors.affiliation: Mutagenesis Unit, IRCCS San Martino University Hospital, IST National Institute for Cancer Research, Department of Health Sciences, University of Genoa, Via A. Pastore 1, Genoa I-16132, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Izzotti
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D005901:Glaucoma / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D014129:Trabecular Meshwork / Q000473:pathology* / Q000502:physiology*
chemical_list: D015415:Biomarkers
keywords: Aqueous humor proteome; Endothelial dysfunction; Extracellular matrix; Glaucoma pathogenesis; Schlemm’s canal; Trabecular meshwork