title: Cone photoreceptor neuroprotection conferred by CNTF in a novel in vivo model of battlefield retinal laser injury.
abstract: OBJECTIVE
  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.
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, Levels 5-6 West Wing, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, United Kingdom.
authors.forename: Sher A
authors.initials: SA
authors.lastname: Aslam
authors.forename: Wayne I L
authors.initials: WI
authors.lastname: Davies
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Singh
authors.forename: Peter
authors.initials: P
authors.lastname: Charbel Issa
authors.forename: Alun R
authors.initials: AR
authors.lastname: Barnard
authors.forename: Robert A H
authors.initials: RA
authors.lastname: Scott
authors.forename: Robert E
authors.initials: RE
authors.lastname: MacLaren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage*; D004247:DNA / Q000235:genetics; D005126:Eye Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005584:Fovea Centralis / Q000293:injuries*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D020287:In Situ Nick-End Labeling; D058449:Intravitreal Injections; D053844:Lasers, Solid-State / Q000009:adverse effects; D051379:Mice; D008822:Mice, Transgenic; D009887:Ophthalmoscopy; D060888:Real-Time Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects
chemical_list: D020934:Ciliary Neurotrophic Factor; D049452:Green Fluorescent Proteins; D004247:DNA
keywords: laser; neurotrophins; scanning laser ophthalmoscopy