title: Retinal Remodeling and Metabolic Alterations in Human AMD.
abstract: Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.
authors.affiliation: Department of Ophthalmology, Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Jones
authors.affiliation: Department of Ophthalmology, Moran Eye Center, University of UtahSalt Lake City, UT, USA; Interdepartmental Program in Neuroscience, University of UtahSalt Lake City, UT, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Pfeiffer
authors.affiliation: Department of Ophthalmology, Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Ferrell
authors.affiliation: Department of Ophthalmology, Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Carl B
authors.initials: CB
authors.lastname: Watt
authors.affiliation: Department of Ophthalmology, University of California, Davis Davis, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Tucker
authors.affiliation: Department of Ophthalmology, Moran Eye Center, University of Utah Salt Lake City, UT, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marc
keywords: Müller cell; age-related macular degeneration (AMD); computational molecular phenotyping (CMP); neural remodeling; photoreceptor; retina; retinal pigment epithelium (RPE); retinal remodeling