CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration.

Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe
loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of
AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during
AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE
cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study
model, we confirmed that hydrogen peroxide (H2O2) induced oxidative stress results in CD44 cell surface receptor
overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative
stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe
(FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we
demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress,
similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative
vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic
cargoes in ocular diseases showing oxidative stress in RPE cells.