Pre-ischemic enriched environment increases retinal resilience to acute ischemic damage in adult rats

Exp Eye Res. 2019 Jan:178:198-211. doi: 10.1016/j.exer.2018.10.007. Epub 2018 Oct 13.

Abstract

Retinal ischemia is a condition associated with several degenerative diseases leading to visual impairment and blindness worldwide. Currently, there is no highly effective therapy for ischemic retinopathies. This study was designed to determine possible benefits of pre-exposure to enriched environment against retinal damage induced by acute ischemia. For this purpose, adult male Wistar rats were randomly assigned to a pre-ischemic standard environment or a pre-ischemic enriched environment for 3 weeks, followed by unilateral ischemia induced by increasing intraocular pressure above 120 mm Hg for 40 min and reperfusion for 1 or 2 weeks in standard environment. Animals were subjected to electroretinography and histological analysis. Pre-ischemic enriched environment afforded significant functional protection in eyes exposed to ischemia/reperfusion injury. A marked reduction in retinal layer thickness, reduced synaptophysin-immunoreactivity and retinal ganglion cell (RGC) number, and increased microglia/macrophage reactivity were observed in ischemic retinas from animals submitted to pre-ischemic standard environment, which were prevented by pre-ischemic enriched environment. A deficit in anterograde transport from the retina to the superior colliculus and the lateral geniculate nucleus was observed in animals exposed to pre-ischemic standard environment, which was lower in animals previously exposed to enriched environment. The exposure to enriched environment before ischemia increased retinal brain derived neurotrophic factor (BDNF) protein levels in ischemic retinas and the administration of ANA-12 (a TrkB antagonist) abolished the protective effect of enriched environment on retinal function and retinal ganglion cell number. These results indicate that pre-ischemic enriched environment increases retinal resilience to acute ischemic damage, possibly through a BDNF/TrkB mediated pathway.

Keywords: Brain derived neurotrophic factor; Ischemia; Pre-ischemic enriched environment; Retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Animal Husbandry / methods*
  • Animals
  • Azepines / pharmacology
  • Benzamides / pharmacology
  • Biomarkers / metabolism
  • Blotting, Western
  • Cholera Toxin / metabolism
  • Electroretinography
  • Environment*
  • Eye Proteins / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Retina / physiopathology
  • Retinal Diseases / metabolism
  • Retinal Diseases / physiopathology
  • Retinal Diseases / prevention & control*
  • Retinal Ganglion Cells / cytology
  • Retinal Vessels / physiopathology

Substances

  • ANA 12 compound
  • Azepines
  • Benzamides
  • Biomarkers
  • Eye Proteins
  • Cholera Toxin