Diminished vision in healthy aging is associated with increased retinal L-type voltage gated calcium channel ion influx

PLoS One. 2013;8(2):e56340. doi: 10.1371/journal.pone.0056340. Epub 2013 Feb 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / physiology*
  • Animals
  • Biological Transport / drug effects
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / metabolism*
  • Gene Expression Regulation / drug effects
  • Health*
  • Magnesium / metabolism
  • Male
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Long-Evans
  • Retina / metabolism*
  • Retina / physiology
  • Vision, Ocular / physiology*

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Protein Isoforms
  • Magnesium