title: The role of proteolytic cellular systems in trabecular meshwork homeostasis.
abstract: The molecular mechanisms contributing to the progressive malfunction of the trabecular meshwork (TM)/Schlemm's canal (SC) conventional outflow pathway during aging and in Primary Open Angle Glaucoma (POAG) are still poorly understood. Progressive accumulation of damaged and cross-linked proteins is a hallmark of aging tissues and has been proposed to play a major role in the tissue abnormalities associated with organismal aging and many age-related diseases. Such progressive accumulation of damaged proteins with age is believed to result from both, increased oxidative stress that results in faster rates of protein damage, as well as from a functional decline in the cellular proteolytic machinery that eliminates misfolded and damaged proteins. Here, we review the reported data that supports the occurrence of oxidative damage and the alterations in the intracellular proteolytic systems in the TM in aging and POAG. Finally, we discuss how the functional decline of the cellular proteolytic machinery in the TM might lead to the observed physiologic alterations of the outflow pathway in glaucoma.
authors.affiliation: Duke University, Department of Ophthalmology, AERI 4004, Durham, NC 27710, USA. paloma.liton@duke.edu
authors.forename: Paloma B
authors.initials: PB
authors.lastname: Liton
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez
authors.forename: David L
authors.initials: DL
authors.lastname: Epstein
mesh_terms: D000375:Aging / Q000502:physiology; D002154:Calpain / Q000502:physiology; D005136:Eye Proteins / Q000378:metabolism; D005902:Glaucoma, Open-Angle / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014129:Trabecular Meshwork / Q000503:physiopathology*
chemical_list: D005136:Eye Proteins; D002154:Calpain; D046988:Proteasome Endopeptidase Complex