Cone photoreceptor neuroprotection conferred by CNTF in a novel in vivo model of battlefield retinal laser injury

Invest Ophthalmol Vis Sci. 2013 Aug 13;54(8):5456-65. doi: 10.1167/iovs.13-11623.

Abstract

Purpose: To develop a reproducible laboratory model to simulate a battlefield foveal laser injury and to test potential neuroprotective effects of a single injection treatment that might be administered in a military setting.

Methods: Frequency-doubled 532-nm Nd:YAG laser was used to induce a threshold retinal injury bilaterally in transgenic reporter mice that have fluorescent cones. Intravitreal injection of ciliary neurotrophic factor (CNTF) was then administered to the lasered eye and compared with a contralateral sham injection of saline. The effect on fluorescent cone cell survival was quantified using a confocal scanning laser ophthalmoscope (cSLO), TUNEL assays, and quantitative real-time PCR (qPCR).

Results: At 3 weeks post-laser, cSLO imaging showed that the proportion of surviving cones expressing green fluorescent protein (GFP) was greater in CNTF-treated (54.1 ± 5.15% of baseline count) than in sham-injected eyes (28.7 ± 4.4%), which was accompanied by a reduction in TUNEL-positive cells. This difference in cone survival persisted at the 6-week point (treated, 39.6 ± 3.2% versus sham, 18.0 ± 3.8%). These changes were accompanied by a reduction in TUNEL-positive cells. The Bcl-2/Bax ratio was increased in CNTF-treated eyes at 1 week postlaser exposure relative to controls.

Conclusions: A single intravitreal injection of CNTF protein was shown to improve cone survival when administered immediately after laser exposure. Similar treatments with CNTF might also have a role in attenuating retinal laser damage sustained by combat personnel in the military setting.

Keywords: laser; neurotrophins; scanning laser ophthalmoscopy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Ciliary Neurotrophic Factor / administration & dosage*
  • DNA / genetics
  • Eye Burns / drug therapy*
  • Eye Burns / metabolism
  • Eye Burns / pathology
  • Fovea Centralis / injuries*
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • In Situ Nick-End Labeling
  • Intravitreal Injections
  • Lasers, Solid-State / adverse effects
  • Mice
  • Mice, Transgenic
  • Ophthalmoscopy
  • Real-Time Polymerase Chain Reaction
  • Retinal Cone Photoreceptor Cells / drug effects*
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Cone Photoreceptor Cells / radiation effects

Substances

  • Ciliary Neurotrophic Factor
  • Green Fluorescent Proteins
  • DNA