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Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration


Senabouth, A and Daniszewski, M and Lidgerwood, GE and Liang, HH and Hernandez, D and Mirzaei, M and Keenan, SN and Zhang, R and Han, X and Neavin, D and Rooney, L and Lopez Sanchez, MIG and Gulluyan, L and Paulo, JA and Clarke, L and Kearns, LS and Gnanasambandapillai, V and Chan, CL and Nguyen, U and Steinmann, AM and McCloy, RA and Farbehi, N and Gupta, VK and Mackey, DA and Bylsma, G and Verma, Nitin and MacGregor, S and Watt, MJ and Guymer, RH and Powell, JE and Hewitt, AW and Pebay, A, Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration, Nature Communications, 13, (1) Article 4233. ISSN 2041-1723 (2022) [Refereed Article]

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DOI: doi:10.1038/s41467-022-31707-4


There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy individuals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Optical technology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Human pain management
UTAS Author:Verma, Nitin (Dr Nitin Verma)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:155594
Year Published:2022
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-03-01
Last Modified:2023-03-01

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