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Maria S. Cortina, Jiucheng He, Tiffany Russ, Nicolas G. Bazan, Haydee E. Bazan; Topical Treatment With Neuroprotectin D1 Increases Corneal Nerve Regeneration After Experimental Surgery. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1982.
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Treatment with pigment epithelial derived factor (PEDF) in association with docosahexaenoic acid (DHA) after lamellar keratectomy increases the regeneration of corneal nerves. We have also shown that corneal sensation returns to normal levels in treated animals at 8 weeks after surgery (Cortina et al, IOVS, 2010). However the mechanism by which PEDF and DHA exert their effect in corneal nerve regeneration is not known. We hypothesize that this effect is due to the synthesis of neuroprotectin D1 (NPD1) from DHA, which increases in corneas treated with PEDF+DHA. The purpose of this study is to define if topical NPD1 treatment increases the regeneration of corneal nerves after surgery.
An 8 mm corneal stromal dissection was performed in the left eyes of adult New Zealand rabbits. The treatment group received topical NPD1 (100ng) application three times a day for 6 weeks. The control group received vehicle drops (2µl of ethanol in 50µl of PBS). Corneal sensitivity was assessed weekly with a Cochet-Bonnet aesthesiometer. Rabbits were sacrificed at 8 weeks and corneas were processed for immunohistochemistry. Corneal nerves were stained with βIII tubulin. The βIII tubulin-positive area at the subepithelial nerve plexus was calculated and compared to the total area using an image analysis program.
Subepithelial corneal nerve area in the NPD1-treated group was increased over two fold compared to the vehicle-treated group (13.08 +/- 2.0 vs 5.85 +/- 1.2). This difference was statistically significant with a p value of 0.006. Six weeks after surgery there was a 67% recovery of corneal sensitivity in the NPD1-treated animals, while in the vehicle-treated group there was only a 30% recovery of sensitivity.
Topical NPD1 treatment promotes functional regeneration of damaged corneal nerves after experimental surgery. This lipid mediator could be a novel therapeutic agent for the treatment of neurotrophic keratitis and dry eye that develops as a result of corneal nerve damage.
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