Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa

Jikui Shen, Xiaoru Yang, Aling Dong, Robert M. Petters, You Wei Peng, Fulton Wong, Peter A. Campochiaro

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Retinitis pigmentosa (RP) is a prevalent cause of blindness caused by a large number of different mutations in many different genes. The mutations result in rod photoreceptor cell death, but it is unknown why cones die. In this study, we tested the hypothesis that cones die from oxidative damage by performing immunohistochemical staining for biomarkers of oxidative damage in a transgenic pig model of RP. The presence of acrolein- and 4-hydroxynonenal- adducts on proteins is a specific indicator that lipid peroxidation has occurred, and there was strong immunofluorescent staining for both in cone inner segments (IS) of two 10-month-old transgenic pigs in which almost all rods had died, compared to faint staining in two 10-month-old control pig retinas. In 22-and 24-month-old transgenic pigs in which all rods and many cones had died, staining was strong in cone axons and some cell bodies as well as IS indicating progression in oxidative damage between 10 and 22 months. Biomarkers for oxidative damage to proteins and DNA also showed progressive oxidative damage to those macromolecules in cones during the course of RP. These data support the hypothesis that the death of rods results in decreased oxygen consumption and hyperoxia in the outer retina resulting in gradual cone cell death from oxidative damage. This hypothesis has important therapeutic implications and deserves rapid evaluation.

Original languageEnglish (US)
Pages (from-to)457-464
Number of pages8
JournalJournal of Cellular Physiology
Volume203
Issue number3
DOIs
StatePublished - Jun 1 2005

Fingerprint

Retinitis Pigmentosa
Cell death
Cones
Cell Death
Swine
Staining and Labeling
Retina
Retinal Photoreceptor Cell Inner Segment
Biomarkers
Acrolein
Retinal Rod Photoreceptor Cells
Mutation
Vertebrate Photoreceptor Cells
Hyperoxia
Blindness
Oxygen Consumption
Lipid Peroxidation
Axons
Proteins
Macromolecules

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Shen, J., Yang, X., Dong, A., Petters, R. M., Peng, Y. W., Wong, F., & Campochiaro, P. A. (2005). Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa. Journal of Cellular Physiology, 203(3), 457-464. https://doi.org/10.1002/jcp.20346

Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa. / Shen, Jikui; Yang, Xiaoru; Dong, Aling; Petters, Robert M.; Peng, You Wei; Wong, Fulton; Campochiaro, Peter A.

In: Journal of Cellular Physiology, Vol. 203, No. 3, 01.06.2005, p. 457-464.

Research output: Contribution to journalArticle

Shen, J, Yang, X, Dong, A, Petters, RM, Peng, YW, Wong, F & Campochiaro, PA 2005, 'Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa', Journal of Cellular Physiology, vol. 203, no. 3, pp. 457-464. https://doi.org/10.1002/jcp.20346
Shen, Jikui ; Yang, Xiaoru ; Dong, Aling ; Petters, Robert M. ; Peng, You Wei ; Wong, Fulton ; Campochiaro, Peter A. / Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa. In: Journal of Cellular Physiology. 2005 ; Vol. 203, No. 3. pp. 457-464.
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