Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa

J Cell Physiol. 2007 Dec;213(3):809-15. doi: 10.1002/jcp.21152.


Retinitis pigmentosa (RP) is a heterogeneous group of diseases in which one of a wide variety of mutations selectively causes rod photoreceptor cell death. After rods die, cone photoreceptors gradually die resulting in blindness. Antioxidants reduce cone cell death in rd1/rd1 mice indicating that cones die from oxidative damage in that model of rapidly progressive RP. In this study, we sought to determine if this observation could be generalized to models of other types of RP, rd10/rd10 mice, a model of more slowly progressive recessive RP, and Q344ter mice, a model of rapidly progressive dominant RP. Compared to appropriate vehicle-treated controls, rd10/rd10 and Q344ter mice treated between P18 and P35 with a mixture of antioxidants previously found to be effective in rd1/rd1 mice showed significantly greater cone survival. Antioxidant-treated rd10/rd10 mice showed preservation of cone function as shown by a significant increase in photopic ERG b-wave amplitudes, and surprisingly showed temporary preservation of scotopic a-wave amplitudes, prolonged rod survival, and slowed depletion of rhodopsin mRNA. These data suggest that oxidative damage contributes to cone cell death regardless of the disease causing mutation that leads to the demise of rods, and that in more slowly progressive rod degenerations, oxidative damage may also contribute to rod cell death. Protection from oxidative damage may be a broadly applicable treatment strategy in RP.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / pharmacology
  • Cell Death / drug effects
  • Codon, Nonsense
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics
  • Disease Models, Animal
  • Drug Administration Schedule
  • Electroretinography
  • Exons
  • Heterozygote
  • Homozygote
  • Injections, Intraperitoneal
  • Kinetics
  • Mice
  • Mice, Mutant Strains
  • Mutation, Missense
  • RNA, Messenger / metabolism
  • Retinal Cone Photoreceptor Cells / drug effects*
  • Retinal Cone Photoreceptor Cells / pathology
  • Retinal Rod Photoreceptor Cells / drug effects*
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology*
  • Rhodopsin / metabolism
  • Thioctic Acid / administration & dosage
  • Thioctic Acid / pharmacology
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / pharmacology


  • Antioxidants
  • Codon, Nonsense
  • RNA, Messenger
  • Thioctic Acid
  • Rhodopsin
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Pde6b protein, mouse
  • alpha-Tocopherol
  • Ascorbic Acid