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

Journal article

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.

Authors: Aslam, SA; Davies, W; Singh, MS; Charbel Issa, P; Barnard, A

• Publication status: Published
• Journal: Investigative ophthalmology and visual science
• Volume: 54
• Issue: 8
• Pages: 5456-5465
• Publication date: 2013-08-01
• DOI: 10.1167/iovs.13-11623
• EISSN: 1552-5783
• ISSN: 0146-0404
• Language: English
• Keywords: Gene Expression Regulation; Real-Time Polymerase Chain Reaction; DNA; Apoptosis; Animals; In Situ Nick-End Labeling; Ophthalmoscopy; Eye Burns; Mice, Transgenic; Ciliary Neurotrophic Factor; Retinal Cone Photoreceptor Cells; Lasers, Solid-State; Cell Survival; Intravitreal Injections; Green Fluorescent Proteins; Fovea Centralis; Mice