title: Inflammation and its role in age-related macular degeneration.
abstract: Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.
authors: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. anu.kauppinen@uef.fi.|Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland. anu.kauppinen@uef.fi.
authors: Anu
authors: http://orcid.org/0000-0001-8254-0200
authors: A
authors: Kauppinen
authors: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Jussi J
authors: JJ
authors: Paterno
authors: Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
authors: Janusz
authors: J
authors: Blasiak
authors: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Antero
authors: A
authors: Salminen
authors: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors: Kai
authors: K
authors: Kaarniranta
mesh_terms: D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D058847:Inflammasomes; D051193:Toll-Like Receptors
keywords: Aging; Eye; Immune system; NLRP3; Retina; Signaling