New Retinal Pigment Epithelial Cell Model to Unravel Neuroprotection Sensors of Neurodegeneration in Retinal Disease

ASATRYAN, A.; CALANDRIA, J.M.; KAUTZMANN, M.A.; JUN, B.; GORDON, W.C.; DO, K.V.; BHATTACHARJEE, S.; PHAM, T.L.; BERMUDEZ, V.; MATEOS, M.V.; HEAP, J.; BAZAN, N.G.

Frontiers in Neuroscience

Fontiers Media SA

Año: 2022

1662-4548

Retinal pigment epithelial (RPE) cells sustain photoreceptor integrity, and when thisfunction is disrupted, retinal degenerations ensue. Herein, we characterize a newcell line from human RPE that we termed ABC. These cells remarkably recapitulatehuman eye native cells. Distinctive from other epithelia, RPE cells originate from theneural crest and follow a neural development but are terminally differentiated into?epithelial? type, thus sharing characteristics with their neuronal lineages counterparts.Additionally, they form microvilli, tight junctions, and honeycomb packing and expressdistinctive markers. In these cells, outer segment phagocytosis, phagolysosome fate,phospholipid metabolism, and lipid mediator release can be studied. ABC cells displayhigher resistance to oxidative stress and are protected from senescence through mTORinhibition, making them more stable in culture. The cells are responsive to NeuroprotectinD1 (NPD1), which downregulates inflammasomes and upregulates antioxidant and antiinflammatorygenes. ABC gene expression profile displays close proximity to nativeRPE lineage, making them a reliable cell system to unravel signaling in uncompensatedoxidative stress (UOS) and retinal degenerative disease to define neuroprotection sites.