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Maria Soledad Cortina, Jiucheng He, Tiffany Russ, Nicolas G. Bazan, Haydee E. P. Bazan; Neuroprotectin D1 Restores Corneal Nerve Integrity and Function After Damage From Experimental Surgery. Invest. Ophthalmol. Vis. Sci. 2013;54(6):4109-4116. doi: 10.1167/iovs.13-12075.
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To investigate if topical treatment of neuroprotectin D1 (NPD1) increases regeneration of functional nerves after lamellar keratectomy.
An 8-mm stromal dissection was performed in the left eye of each rabbit. The rabbits were treated with NPD1, pigment epithelial-derived factor (PEDF) in combination with docosahexaenoic acid (DHA) or vehicle for 6 weeks, and corneas were obtained at 8 weeks. After fixation, corneal wholemounts were stained with mouse monoclonal anti-βIII-tubulin antibody and double stained with chicken anti-calcitonin gene-related peptide (CGRP) antibody. Corneal sensitivity and tear secretion were measured using the Cochet-Bonnet esthesiometer and the Schirmer's test, respectively. Additional rabbits were treated with NPD1, PEDF+DHA, or vehicle, and corneal sections were stained with a rat monoclonal anti-neutrophil antibody. Cultures of trigeminal ganglia from 5-day-old mice were treated with NPD1, PEDF+DHA, lipoxin A4 (LXA4), 12- or 15-hydroxyeicosatetraenoic acid (12[S] or 15[S]-HETE), and nerve growth factor (NGF) as positive control.
NPD1 increased subepithelial corneal nerve area three times compared with vehicle-treated rabbits. The effect was similar to PEDF+DHA–treated animals. There was recovery of CGRP-positive neurons and an increase in corneal sensitivity and tear secretion in NPD1-treated animals. NPD1 decreased neutrophil infiltration after 2 and 4 days of treatment. In the in vitro cultures, NPD1 and PEDF+DHA induced a 3-fold increase in neurite outgrowth compared with cultures without supplementation. Treatments with LXA4, 12(S)-, and 15(S)- HETE did not stimulate neurite outgrowth.
NPD1 has anti-inflammatory and nerve regenerative properties. This study demonstrates that NPD1 may offer an effective treatment for neurotrophic corneas.
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