Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice

Exp Eye Res. 2015 Jun:135:59-66. doi: 10.1016/j.exer.2015.03.023. Epub 2015 Apr 25.

Abstract

Retinal ageing results in chronic inflammation, extracellular deposition, including that of amyloid beta (Aβ) and declining visual function. In humans this can progress into age-related macular degeneration (AMD), which is without cure. Therapeutic approaches have focused on systemic immunotherapies without clinical resolution. Here, we show using aged mice that 2-Hydroxypropyl-β-cyclodextrin, a sugar molecule given as eye drops over 3 months results in significant reductions in Aβ by 65% and inflammation by 75% in the aged mouse retina. It also elevates retinal pigment epithelium specific protein 65 (RPE65), a key molecule in the visual cycle, in aged retina. These changes are accompanied by a significant improvement in retinal function measured physiologically. 2-Hydroxypropyl-β-cyclodextrin is as effective in reducing Aβ and inflammation in the complement factor H knockout (Cfh(-/-)) mouse that shows advanced ageing and has been proposed as an AMD model. β-cyclodextrin is economic, safe and may provide an efficient route to reducing the impact of retinal ageing.

Keywords: Cyclodextrin; Lipid; RPE65; Retinal ageing; Retinal amyloid beta; Retinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Aging / physiology*
  • Amyloid beta-Peptides / metabolism*
  • Analysis of Variance
  • Animals
  • Complement C3 / metabolism
  • Disease Models, Animal
  • Electroretinography / drug effects
  • Inflammation / drug therapy*
  • Membrane Lipids / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Retina / drug effects*
  • Retina / physiology
  • beta-Cyclodextrins / administration & dosage
  • beta-Cyclodextrins / pharmacology*
  • cis-trans-Isomerases / metabolism

Substances

  • Amyloid beta-Peptides
  • Complement C3
  • Membrane Lipids
  • beta-Cyclodextrins
  • retinoid isomerohydrolase
  • cis-trans-Isomerases