Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice.
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.
Institute of Ophthalmology, University College London, UK.
Jaimie
J
Hoh Kam
Institute of Ophthalmology, University College London, UK.
Aisling
A
Lynch
Institute of Ophthalmology, University College London, UK.
Rana
R
Begum
Institute of Ophthalmology, University College London, UK.
Alex
A
Cunea
Institute of Ophthalmology, University College London, UK. Electronic address: g.jeffery@ucl.ac.uk.
Glen
G
Jeffery
D000287:Administration, Topical; D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology*; D019745:cis-trans-Isomerases / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
D016229:Amyloid beta-Peptides; D003176:Complement C3; D008563:Membrane Lipids; D047392:beta-Cyclodextrins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
Cyclodextrin; Lipid; RPE65; Retinal ageing; Retinal amyloid beta; Retinal inflammation