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

Sher A. Aslam, Wayne I.L. Davies, Mandeep S. Singh, Peter Charbel Issa, Alun R. Barnard, Robert A.H. Scott, Robert E. MacLaren

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5456-5465
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number8
DOIs
StatePublished - Aug 20 2013

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Keywords

  • Laser
  • Neurotrophins
  • Scanning laser ophthalmoscopy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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