Comparative transport analysis of cell penetrating peptides and Lysosomal sequences for selective tropism towards RPE cells.

Cell penetrating peptides are typically nonspecific, targeting multiple cell types without discrimination. However, subsets of Cell penetrating peptides (CPP) have been found, which show a 'homing' capacity or increased likelihood of internalizing into specific cell types and subcellular locations. Therapeutics intended to be delivered to tissues with a high degree of cellular diversity, such as the intraocular space, would benefit from delivery using CPP that can discriminate across multiple cell types.

Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis.

Fenretinide is a synthetic retinoid pharmaceutical linked to ceramide build-up . Saposin D is an intralysosomal protein necessary for ceramide binding/degradation. We show, electronic absorption spectroscopy, fluorescence spectroscopy, and ceramide hydrolysis assays, that fenretinide is bound by saposin D { = (1.

Recombinant Manganese Peroxidase Reduces A2E Burden in Age-Related and Stargardt's Macular Degeneration Models.

Macular degeneration is hallmarked by retinal accumulation of toxic retinoid species (e.g., A2E) for which there is no endogenous mechanism to eliminate it.

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

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 HO-dependent enzymatic oxidation by horseradish peroxidase and photooxidation by blue light (=450-460 nm).