Open AccessOral Delivery of the P2Y12Receptor Antagonist Ticagrelor Prevents Loss of Photoreceptors in an ABCA4−/−Mouse Model of Retinal Degeneration
Author(s) -
Wennan Lu,
Keith E. Campagno,
Huen-Yee Tso,
Aurora Cenaj,
Alan M. Laties,
Leif Carlsson,
Claire H. Mitchell
Publication year - 2019
Publication title -
investigative ophthalmology and visual science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.935
H-Index - 218
eISSN - 1552-5783
pISSN - 0146-0404
DOI - 10.1167/iovs.19-27241
Subject(s) - ticagrelor , abca4 , antagonist , retinal degeneration , p2y receptor , chemistry , receptor antagonist , pharmacology , retinal , receptor , medicine , agonist , biochemistry , aspirin , clopidogrel , gene , phenotype
Accumulation of lysosomal waste is linked to neurodegeneration in multiple diseases, and pharmacologic enhancement of lysosomal activity is hypothesized to reduce pathology. An excessive accumulation of lysosomal-associated lipofuscin waste and an elevated lysosomal pH occur in retinal pigment epithelial cells of the ABCA4-/- mouse model of Stargardt's retinal degeneration. As treatment with the P2Y12 receptor antagonist ticagrelor was previously shown to lower lysosomal pH and lipofuscin-like autofluorescence in these cells, we asked whether oral delivery of ticagrelor also prevented photoreceptor loss.