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Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):E1402-8. doi: 10.1073/pnas.1400530111. Epub 2014 Mar 24.

Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium.

Author information

1
Margaret Dyson Vision Research Institute, Department of Biochemistry, and Department of Physiology, Weill Cornell Medical College of Cornell University, New York, NY 10065.

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.

KEYWORDS:

aging; lipofuscinosis; residual bodies; retinopathy

PMID:
24706818
PMCID:
PMC3986126
DOI:
10.1073/pnas.1400530111
[Indexed for MEDLINE]
Free PMC Article

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