Serum-deprivation response of ARPE-19 cells; expression patterns relevant to age-related macular degeneration

• DOI: 10.1101/2023.10.12.562023
• Publication Date: 2023-10-13T02:50:28Z
• Authors: Katherine M. Pete...; Sanghamitra Mishra; Esther Asaki; John I. Powell; Yiwen He; Alan E. Berger; Dinusha Rajapakse; Graeme Wistow
• Keywords: Bruch's membrane

Abstract ARPE-19 cells are derived from adult human retinal pigment epithelium (RPE). The response of these to the stress serum deprivation mimics some important processes relevant age-related macular degeneration (AMD). Here we extend characterization this using RNASeq and EGSEA gene set analysis over nine days deprivation. This experiment confirmed up-regulation cholesterol lipid-associated pathways that increase levels in cells. expression also identified other AMD progression. There were significant changes extracellular matrix expression, notably a switch collagen IV, key component Bruch’s membrane (part blood-retina barrier), fibrosis-like type I matrix. Changes profile led discovery amelotin is induced associated with development calcium deposits seen late-stage geographic atrophy. transcriptional profiles pathways, including inflammation, complement, coagulation, modified, consistent immune patterns AMD. As previously noted, resist apoptosis autophagy but instead initiate pattern characteristic senescence, maintenance barrier function even as aspects RPE compromised. Other differentially regulated genes open new avenues for investigation. Our results suggest maintain responses native informative such, they provide convenient system testing potential therapeutic interventions.