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

Joe M Butler, Wasu Supharattanasitthi, Yit C Yang, Luminita Paraoan

Research output: Contribution to journalArticle (journal)peer-review

7 Citations (Scopus)
1 Downloads (Pure)

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 × 10-6 ). 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.

Original languageEnglish
Pages (from-to)5572-5585
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number12
Early online date1 Jun 2021
DOIs
Publication statusPublished - 7 Jun 2021
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Eye Proteins/genetics
  • Gene Expression Regulation
  • Humans
  • Middle Aged
  • RNA-Seq/methods
  • Retinal Pigment Epithelium/metabolism
  • Transcription, Genetic
  • Transcriptome
  • Visual Pathways/metabolism

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