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YingHsuan Shih, Lindsay Johanna Bailey-Steinitz, Monte J Radeke, Peter Coffey; RPE wound healing and its association with AMD. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2284.
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Retinal pigmented epithelium (RPE) is at risk of exposure to various cytotoxic elements. The persistent existence or reoccurrence of these stressors may repetitively damage RPE and lead to age-related macular degeneration (AMD). However, how RPE cells response to nearby damage remains elusive. Here, we developed a cell-based model to investigate the response of differentiated RPE to acute and chronic wounding and assess its association with AMD.
Fetal RPE cells were cultured on ECIS plates and differentiated for 32 days. Electrical pulses were repetitively delivered via electrodes on the bottom of the plates to create a chronic wound. Monolayer repair was accessed based on behavioral, morphological, and transcriptomic measures. Gene expression profiles of wounded RPE were compared with published AMD microarray data to evaluate our model system with disease pathogenesis.
Human RPE used both migration and proliferation to repair lesions on the monolayer. Both properties were enhanced following repetitive wounding; the rate of migration increased 30% and the percentage of proliferative cells doubled, yet the RPE failed to restore their original cell morphology. Also, a systemic increase of epithelial-to-mesenchymal transition and cell cycle genes was detected in the repetitively wounded RPE. In addition, we observed a systemic decrease of genes associated with RPE functions, including visual cycle enzymes and RPE transcription factors. Expression levels of these RPE genes were restored within 24-hours, but the extent of recovery diminished after chronic wounding. Moreover, misregulation of genes associated with inflammation (IL-6, IL-18, CCL2) and apoptosis was detected. Importantly, there is a significant enrichment of geographic atrophy (GA)-associated genes in wounded cells.
We developed a cell-based model to study the acute and the chronic wound response of human RPE. RPE use both migration and proliferation to repair the damaged region, however the cells failed to fully repair after chronic wounding. Repetitive wounding also led to changes on behavioral, morphological, and transcriptomic levels. In particular, the negative effect on RPE genes expression might cause the progressive decline of RPE functions and retinal cell degeneration in aged eyes. The misregulation of inflammation, apoptosis, and GA-associated genes suggests that RPE wound healing may play a part in AMD pathogenesis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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