title: Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is an eye disease underlined by the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillares, but the exact mechanism of cell death in AMD is not completely clear. This mechanism is important for prevention of and therapeutic intervention in AMD, which is a hardly curable disease. Present reports suggest that both apoptosis and pyroptosis (cell death dependent on caspase-1) as well as necroptosis (regulated necrosis dependent on the proteins RIPK3 and MLKL, caspase-independent) can be involved in the AMD-related death of RPE cells. Autophagy, a cellular clearing system, plays an important role in AMD pathogenesis, and this role is closely associated with the activation of the NLRP3 inflammasome, a central event for advanced AMD. Autophagy can play a role in apoptosis, pyroptosis, and necroptosis, but its contribution to AMD-specific cell death is not completely clear. Autophagy can be involved in the regulation of proteins important for cellular antioxidative defense, including Nrf2, which can interact with p62/SQSTM, a protein essential for autophagy. As oxidative stress is implicated in AMD pathogenesis, autophagy can contribute to this disease by deregulation of cellular defense against the stress. However, these and other interactions do not explain the mechanisms of RPE cell death in AMD. In this review, we present basic mechanisms of autophagy and its involvement in AMD pathogenesis and try to show a regulatory role of autophagy in RPE cell death. This can result in considering the genes and proteins of autophagy as molecular targets in AMD prevention and therapy.
authors.affiliation: Department of Ophthalmology, University of Eastern Finland, 70210, Kuopio, Finland.|Department of Ophthalmology, Kuopio University Hospital, 70210, Kuopio, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.affiliation: Department of Molecular Genetics, University of Lodz, 90-236, Lodz, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Tokarz
authors.affiliation: Department of Ophthalmology, University of Eastern Finland, 70210, Kuopio, Finland.
authors.forename: Ali
authors.initials: A
authors.lastname: Koskela
authors.affiliation: Department of Ophthalmology, University of Eastern Finland, 70210, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Paterno
authors.affiliation: Department of Molecular Genetics, University of Lodz, 90-236, Lodz, Poland. jblasiak@biol.uni.lodz.pl.
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002470:Cell Survival; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology / Q000473:pathology*; D008954:Models, Biological; D055213:Retinal Pigment Epithelium / Q000473:pathology*
keywords: Age-related macular degeneration; Alu transcripts; Apoptosis; Cell death; Necroptosis; Pyroptosis