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

1 Citation (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
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

Fingerprint Dive into the research topics of 'CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration'. Together they form a unique fingerprint.

  • Cite this