title: Diminished vision in healthy aging is associated with increased retinal L-type voltage gated calcium channel ion influx.
abstract: Extensive evidence implicates an increase in hippocampal L-type voltage-gated calcium channel (L-VGCC) expression, and ion influx through these channels, in age-related cognitive declines. Here, we ask if this "calcium hypothesis" applies to the neuroretina: Is increased influx via L-VGCCs related to the well-documented but poorly-understood vision declines in healthy aging? In Long-Evans rats we find a significant age-related increase in ion flux through retinal L-VGCCs in vivo (manganese-enhanced MRI (MEMRI)) that are longitudinally linked with progressive vision declines (optokinetic tracking). Importantly, the degree of retinal Mn(2+) uptake early in adulthood significantly predicted later visual contrast sensitivity declines. Furthermore, as in the aging hippocampus, retinal expression of a drug-insensitive L-VGCC isoform (α1D) increased - a pattern confirmed in vivo by an age-related decline in sensitivity to L-VGCC blockade. These data highlight mechanistic similarities between retinal and hippocampal aging, and raise the possibility of new treatment targets for minimizing vision loss during healthy aging.
authors: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States of America.
authors: David
authors: D
authors: Bissig
authors: Dennis
authors: D
authors: Goebel
authors: Bruce A
authors: BA
authors: Berkowitz
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006262:Health; D008274:Magnesium / Q000378:metabolism; D008297:Male; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000378:metabolism* / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020033:Protein Isoforms; D008274:Magnesium