Saposin B Binds the Lipofuscin Bisretinoid A2E and Prevents its Enzymatic and Photooxidation

Abstract

Vitamin A based bisretinoid accumulation is a major focus in the study of macular degeneration. Whether specific endogenous lysosomal proteins can bind A2E, a pronounced bisretinoid in lipofuscin granules in retinal pigment epithelial cells, and interfere with enzymatic or photoinduced oxidation of such, has not been explored. Herein, using fluorescence and electronic absorption spectroscopy and mass spectrometry, we demonstrate that Saposin B, a critical protein in the degradation of sulfatides and "flushing" of lipids, can bind A2E, preventing its H 2 O 2 -dependent enzymatic oxidation by horseradish peroxidase and photooxidation by blue light (λ=450-460 nm). Putting a lid on itDegrading bisretenoids, understanding their cellular photochemistry and tracking their effects on cellular processes are critical in the study of age-related macular degeneration (AMD) development and treatment. Herein, we demonstrate that the vital cellular co-factor Saposin B binds A2E, a common bisretenoid found in granules in AMD patients, and prevents enzymatic and photooxidation/ degradation.Correspondence to: Fadi Bou-Abdallah; Robert P. Doyle. Conflict of interestThe authors declare no conflict of interest.Supporting Information (also containing the Experimental Section) and the ORCID identification number(s) for the author(s) of this article can be found under: http://dx