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Maria Cortina, Jiucheng He, Azucena Kakazu, Nicolas Bazan, Haydee Bazan; The PEDF neuroprotective domain plus DHA selectively induces corneal nerve regeneration after experimental surgery. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3117.
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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). Some therapeutic advantages of using smaller peptides include better tissue penetration, a narrower spectrum of action with reduced side effects, and ease of synthesis in reproducibly large-scale quantities. The purpose of this study was to compare the effect of two PEDF derivatives: a 44 mer-PEDF that has neurotrophic activity and a 34 mer-PEDF with antiangiogenic properties in association with DHA in corneal nerve regeneration after experimental surgery.
An 8 mm corneal stromal dissection was performed in the left eyes of adult New Zealand rabbits. Treatment groups received topical PEDF+DHA; 34 mer-PEDF+DHA or 44 mer-PEDF+DHA by means of a 72 h collagen shield for 6 weeks. The control group received vehicle. 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.
Six weeks after surgery there was a 73% recovery of corneal sensitivity in the 44 mer-PEDF+DHA-treated animals, while in the 34 mer-PEDF+DHA and vehicle-treated groups only 54 and 43% of corneal sensitivity was recovered, respectively. Subepithelial corneal nerve area in the 44 mer-PEDF+DHA-treated group was increased over two-fold compared to the 34 mer-PEDF+DHA- and vehicle-treated groups (8.65 +/- 0.6; 4.19 +/- 0.7; 4.45+/- 0.9). This difference was statistically significant with a p value of 0.003.
The 44 mer-PEDF, with neurotrophic activity in combination with DHA, promotes functional regeneration of damaged corneal nerves after experimental surgery while 34 mer-PEDF does not have significant activity in corneal nerve regeneration. 44 mer-PEDF could be a novel therapeutic agent of easier synthesis and better bioavailability than the complete PEDF molecule for the treatment of neurotrophic keratitis and dry eye that develops as a result of corneal nerve damage.
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