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

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
JournalBiochemistry and Biophysics Reports
Volume18
Early online date1 May 2019
DOIs
Publication statusPublished - Jul 2019
MoE publication typeA1 Journal article-refereed

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Retinal Pigments
Macular Degeneration
Lysosomes
Oxidative stress
Epithelial Cells
Oxidative Stress
Cell death
Cell Death
Proliferative Vitreoretinopathy
Eye Diseases
Fluorescein-5-isothiocyanate
Cell Surface Receptors
Fluorescent Dyes
Neurodegenerative Diseases
Nucleic Acids
Hydrogen Peroxide
Health
Cell Line
Molecules

Keywords

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

Cite this

Chandola, Chetan ; Casteleijn, Marco G. ; Chandola, Urvashi M. ; Gopalan, Lakshmi Narayanan ; Urtti, Arto ; Neerathilingam, Muniasamy. / CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration. In: Biochemistry and Biophysics Reports. 2019 ; Vol. 18.
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CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration. / Chandola, Chetan; Casteleijn, Marco G.; Chandola, Urvashi M.; Gopalan, Lakshmi Narayanan; Urtti, Arto; Neerathilingam, Muniasamy.

In: Biochemistry and Biophysics Reports, Vol. 18, 100642, 07.2019.

Research output: Contribution to journalArticleScientificpeer-review

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