Publication: RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription
Issued Date
2021-06-01
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ISSN
15821838
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2-s2.0-85107321784
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Cellular and Molecular Medicine. Vol.25, No.12 (2021), 5572-5585
Suggested Citation
Joe M. Butler, Wasu Supharattanasitthi, Yit C. Yang, Luminita Paraoan RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription. Journal of Cellular and Molecular Medicine. Vol.25, No.12 (2021), 5572-5585. doi:10.1111/jcmm.16569 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76160
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Title
RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription
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.