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

Chetan Chandola, Marco G. Casteleijn, Urvashi M. Chandola, Lakshmi Narayanan Gopalan, Arto Urtti, Muniasamy Neerathilingam

    Research output: Contribution to journalArticleScientificpeer-review

    5 Citations (Scopus)

    Abstract

    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 (H 2 O 2 ) 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.

    Original languageEnglish
    Article number100642
    Pages (from-to)100642
    JournalBiochemistry and Biophysics Reports
    Volume18
    Early online date1 May 2019
    DOIs
    Publication statusPublished - Jul 2019
    MoE publication typeA1 Journal article-refereed

    Keywords

    • Age-related macular degeneration
    • CD44 aptamer
    • Lysosomal delivery
    • Oxidative stress
    • RPE cells
    • Targeted delivery

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