Effects of selective elimination of senescent cells on RPE/choroid complex in mice with subretinal drusenoid deposits
The target deletion of ATP binding cassette subfamily member 1 (ABCA1) and G1 (ABCG1) in myeloid cells leads to subretinal drusenoid deposits in mice (Abca1/g1 -m/-m). We here report the selective elimination of p16-positive cells results in the significant eduction in myeloid markers, pro-inflammatory cytokines and prostaglandin biosynthetic enzymes. Overall design: INK-ATTAC mice are transgenic mice expressing FKBP-caspase 8 fusion protein under INK4a promoter. p16Ink4a-positive senescent cells can be effectively ablated by the administration of AP20187 which dimerizes the fusion protein and selectively induce apoptosis of p16-positive senescent cells.To ablate p16Ink4a-positive cells, Abca1/g1 -m/-m; INK-ATTAC mice were treated with intraperitoneal injection of AP20187 every other day for 3 months. RPE/choroid complex samples were collected from eyes.