title: Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans.
abstract: Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD.
authors: School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
authors: Othman
authors: 0000-0001-9315-8824
authors: O
authors: Al Gwairi
authors: School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia.
authors: Lyna
authors: L
authors: Thach
authors: Faculty of Health Sciences, University of Macau, Taipa, Macau; Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510006, China.
authors: Wenhua
authors: W
authors: Zheng
authors: School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia; Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.
authors: Narin
authors: N
authors: Osman
authors: School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia; School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia.
authors: Peter J
authors: 0000-0002-0335-3835
authors: PJ
authors: Little