Increased susceptibility to fundus camera-delivered light-induced retinal degeneration in mice deficient in oxidative stress response proteins

Yi Ding, Bogale Aredo, Xin Zhong, Cynthia X. Zhao, Rafael L. Ufret-Vincenty

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Oxidative stress is an important contributor to the pathogenesis of many retinal diseases including age-related macular degeneration and retinal dystrophies. Light-induced retinal degeneration (LIRD) can serve as a model in which to study the response of the retina to stress. Of note, many genetic mutant mice are in a C57BL/6 J background and are thus resistant to the usual LIRD models. We recently developed a new model of fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) which is effective in strains of mice expressing the light-resistant variant of RPE65 (450Met), including C57BL/6 J. In this work we investigated whether FCD-LIRD would be useful as a model in which to test the effect of genetic mutations on the response of the retina to stress. Furthermore, we tested whether oxidative stress plays an important role in the setting of this new FCD-LIRD model. FCD-LIRD was applied to C57BL/6 J mice and to mice simultaneously deficient in three proteins that are important in the response of the retina to oxidative stress (SOD1, DJ-1 and Parkin). Using fundus photography, we found that retinal damage was dramatically increased in the SOD1/DJ-1/Parkin deficient mice compared to C57BL/6 J. Outer retinal OCT volume and RPE cell morphology analysis in ZO-1-stained flat mounts added support to these findings. Gene expression analysis confirmed a strong oxidative stress response after FCD-LIRD, which was differentially altered in the SOD1/DJ1/Parkin deficient mice. We conclude that FCD-LIRD is useful to study the effect of genetic mutations on the response of the retina to light stress in light-resistant strains of mice. Furthermore, oxidative stress seems to be an important component of FCD-LIRD. Finally, we have established protocols to quantify the effect of FCD-LIRD on the retina and RPE which will be useful for future studies. Further dissection of the mechanisms by which the retina responds to light-induced oxidative stress may result in new strategies to modulate this response, which could lead to a reduction in retinal and RPE damage.

Original languageEnglish (US)
Pages (from-to)58-68
Number of pages11
JournalExperimental Eye Research
Volume159
DOIs
StatePublished - Jun 1 2017

Fingerprint

Retinal Degeneration
Heat-Shock Proteins
Oxidative Stress
Light
Retina
Macular Degeneration
Retinal Dystrophies
Retinal Diseases
Mutation
Photography
Inbred C57BL Mouse
Cell Size
Dissection

Keywords

  • Light induced retinal degeneration
  • Met450
  • OCT volume
  • Oxidative stress
  • Retina
  • RPE morphology
  • RPE65

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Increased susceptibility to fundus camera-delivered light-induced retinal degeneration in mice deficient in oxidative stress response proteins. / Ding, Yi; Aredo, Bogale; Zhong, Xin; Zhao, Cynthia X.; Ufret-Vincenty, Rafael L.

In: Experimental Eye Research, Vol. 159, 01.06.2017, p. 58-68.

Research output: Contribution to journalArticle

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