RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription

Butler, Joe M, Supharattanasitthi, Wasu, Yang, Yit C and Paraoan, Luminita ORCID: 0000-0001-7568-7116 (2021) RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 25 (12). pp. 5572-5585.

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Official URL: http://dx.doi.org/10.1111/jcmm.16569

Abstract

Ageing presents adverse effects on the retina and is the primary risk factor for age-related macular degeneration (AMD). We report the first RNA-seq analysis of age-related transcriptional changes in the human retinal pigment epithelium (RPE), the primary site of AMD pathogenesis. Whole transcriptome sequencing of RPE from human donors ranging in age from 31 to 93 reveals that ageing is associated with increasing transcription of main RPE-associated visual cycle genes (including LRAT, RPE65, RDH5, RDH10, RDH11; pathway enrichment BH-adjusted P = 4.6 × 10<sup>-6</sup> ). This positive correlation is replicated in an independent set of 28 donors and a microarray dataset of 50 donors previously published. LRAT expression is positively regulated by retinoid by-products of the visual cycle (A2E and all-trans-retinal) involving modulation by retinoic acid receptor alpha transcription factor. The results substantiate a novel age-related positive feedback mechanism between accumulation of retinoid by-products in the RPE and the up-regulation of visual cycle genes.

Item Type:	Article
Uncontrolled Keywords:	A2E, ageing, LRAT, macular degeneration, retinal pigment epithelium, retinol metabolism, RNA&#8208, seq, RDH5, RDH10, RDH11, RPE65, visual cycle
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	10 May 2021 09:39
Last Modified:	18 Jan 2023 22:49
DOI:	10.1111/jcmm.16569
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3121788