Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium Academic Article uri icon

Overview

MeSH Major

  • Lipofuscin
  • Retinal Pigment Epithelium
  • Retinoids
  • beta-Cyclodextrins

abstract

  • Accumulation of lipofuscin bisretinoids (LBs) in the retinal pigment epithelium (RPE) is the alleged cause of retinal degeneration in genetic blinding diseases (e.g., Stargardt) and a possible etiological agent for age-related macular degeneration. Currently, there are no approved treatments for these diseases; hence, agents that efficiently remove LBs from RPE would be valuable therapeutic candidates. Here, we show that beta cyclodextrins (β-CDs) bind LBs and protect them against oxidation. Computer modeling and biochemical data are consistent with the encapsulation of the retinoid arms of LBs within the hydrophobic cavity of β-CD. Importantly, β-CD treatment reduced by 73% and 48% the LB content of RPE cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively. Furthermore, intravitreal administration of β-CDs reduced significantly the content of bisretinoids in the RPE of DKO animals. Thus, our results demonstrate the effectiveness of β-CDs to complex and remove LB deposits from RPE cells and provide crucial data to develop novel prophylactic approaches for retinal disorders elicited by LBs.

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3986126

Digital Object Identifier (DOI)

  • 10.1073/pnas.1400530111

PubMed ID

  • 24706818

Additional Document Info

start page

  • E1402

end page

  • 8

volume

  • 111

number

  • 14