Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage

J Neurochem. 2012 Apr;121(1):146-56. doi: 10.1111/j.1471-4159.2012.07647.x. Epub 2012 Feb 9.


All-trans-retinal and its condensation-products can cause retinal degeneration in a light-dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt's disease and age-related macular degeneration. Although these toxic retinoid by-products originate from rod and cone photoreceptor cells, the contribution of each cell type to light-induced retinal degeneration is unknown. In this study, the primary objective was to learn whether rods or cones are more susceptible to light-induced, all-trans-retinal-mediated damage. Previously, we reported that mice lacking enzymes that clear all-trans-retinal from the retina, ATP-binding cassette transporter 4 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy. We first examined early-stage age-related macular degeneration patients and found retinal degenerative changes in rod-rich rather than cone-rich regions of the macula. We then evaluated transgenic mice with rod-only and cone-like-only retinas in addition to progenies of such mice inbred with Rdh8(-/-) Abca4(-/-) mice. Of all these strains, Rdh8(-/-) Abca4(-/-) mice with a mixed rod-cone population showed the most severe retinal degeneration under regular cyclic light conditions. Intense light exposure induced acute retinal damage in Rdh8(-/-) Abca4(-/-) and rod-only mice but not cone-like-only mice. These findings suggest that progression of retinal degeneration in Rdh8(-/-) Abca4(-/-) mice is affected by differential vulnerability of rods and cones to light.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / drug effects
  • ATP-Binding Cassette Transporters / genetics
  • Aged
  • Aged, 80 and over
  • Alcohol Oxidoreductases / deficiency
  • Alcohol Oxidoreductases / genetics
  • Animals
  • Cell Differentiation* / physiology
  • Disease Progression
  • Female
  • Humans
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Photic Stimulation / adverse effects*
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Cone Photoreceptor Cells / pathology*
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Retinal Rod Photoreceptor Cells / metabolism
  • Retinal Rod Photoreceptor Cells / pathology*


  • ATP-Binding Cassette Transporters
  • Abca4 protein, mouse
  • Alcohol Oxidoreductases
  • Rdh8 protein, mouse