Neuroprotection in the juvenile rat model of light-induced retinopathy: evidence suggesting a role for FGF-2 and CNTF

Invest Ophthalmol Vis Sci. 2007 May;48(5):2311-20. doi: 10.1167/iovs.06-1205.

Abstract

Purpose: In a former study, it was demonstrated that the retina of juvenile Sprague-Dawley (SD) rat has a remarkable intrinsic resistance to light-induced retinopathy compared with the adult retina. The purpose of the present study was to investigate the cellular and molecular mechanisms underlying this endogenous resistance to light-induced damage.

Methods: Juvenile SD rats were exposed for 6 (from P14 to P20) or 14 (from P14 to P28) days to a bright, cyclic, luminous environment of 10,000 lux. Retinal histology was examined immediately after exposure to light or at 2 months of age, and photoreceptor cell death was quantified by measuring the thickness of the outer nuclear layer (ONL) and by TUNEL assays. Changes in protein levels and cellular localization of fibroblast growth factor (FGF)-2, ciliary neurotrophic factor (CNTF), and brain-derived neurotrophic factor (BDNF) were determined by Western blot analysis and retinal immunohistochemistry, respectively.

Results: The data demonstrate that although the rate of photoreceptor loss was different after 6 and 14 days of exposure to light, similar ONL thickness was reached at 2 months of age--that is, 4 to 5 weeks after exposure to light. A large number of TUNEL-positive photoreceptors was visualized immediately after 6 and 14 days of exposure to light, reflecting the intense cell death that was occurring in the ONL. Western blot analysis showed that exposure to light induced a strong upregulation of the neurotrophic factors FGF-2 and CNTF in juvenile retinas, whereas no change in BDNF protein expression was noted. Of interest, after exposure to light, endogenous FGF-2 and CNTF were selectively upregulated in Müller cells.

Conclusions: The results show that endogenous expression of FGF-2 and CNTF by Müller glia may play a role in protecting the juvenile retina from light-induced damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Death
  • Ciliary Neurotrophic Factor / metabolism*
  • Cytoprotection
  • Disease Models, Animal
  • Female
  • Fibroblast Growth Factor 2 / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • In Situ Nick-End Labeling
  • Microscopy, Fluorescence
  • Neuroprotective Agents / metabolism*
  • Pregnancy
  • Radiation Injuries, Experimental / metabolism*
  • Radiation Injuries, Experimental / pathology
  • Radiation Injuries, Experimental / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Retina / metabolism
  • Retina / pathology
  • Retina / radiation effects*
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology
  • Retinal Degeneration / prevention & control
  • Up-Regulation

Substances

  • Brain-Derived Neurotrophic Factor
  • Ciliary Neurotrophic Factor
  • Neuroprotective Agents
  • Fibroblast Growth Factor 2