A Mouse Model of Retinal Recovery From Photo-Oxidative/Photo-Inflammatory Injury: Nrf2, SOD1, DJ-1, and Parkin Are Not Essential to Recovery

Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):1165-1174. doi: 10.1167/iovs.18-25751.

Abstract

Purpose: To determine if there is structural and functional recovery of the retina from light induced retinal degeneration, and to evaluate the role of the oxidative stress response elements Nrf2, SOD1, DJ-1, and Parkin in such a recovery process.

Methods: Eyes from C57BL/6J (B6J) mice and from oxidative stress response-deficient strains of mice were treated with intense light using the fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) model. Fundus photographs, optical coherence tomography (OCT) images, and electroretinography (ERG) responses were obtained before the injury, during the "maximal injury phase" (days 4-7) and during the "recovery phase" (days 14-16) post light exposure and were evaluated for retinal damage and assessed for evidence of recovery from the injury.

Results: We demonstrate that mice treated with a sub-lethal FCD-LIRD protocol show an initial acute retina injury phase peaking between days 4 to 7 followed by a recovery phase in which the outer retinal thickness/volume and retinal function partially recover. These observations are reproduced in B6J mice and in mice lacking oxidative stress response enzymes (SOD1, DJ-1, and Parkin) or the oxidative stress response master regulator Nrf2.

Conclusions: Our data indicate that retinal recovery from injury can proceed via pathways that are independent from the common oxidative stress response elements Nrf2, SOD1, DJ-1, and Parkin. Furthermore, the model of retinal recovery from injury that we describe here mimics changes seen in a variety of clinical entities and may provide an excellent platform for dissecting general pathways of retinal recovery from sub-lethal injury.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Electroretinography
  • Female
  • Light / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress
  • Photography
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / physiopathology*
  • Recovery of Function / physiology*
  • Retina / diagnostic imaging
  • Retina / physiopathology
  • Retina / radiation effects
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / physiopathology*
  • Superoxide Dismutase-1 / metabolism*
  • Tomography, Optical Coherence
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Sod1 protein, mouse
  • Superoxide Dismutase-1
  • Ubiquitin-Protein Ligases
  • parkin protein