Role of Neuronal Growth Promoting Factors on Nerve Regeneration Following LASIK

Abstract

Abstract: : Purpose: To investigate the role of topically administered factors for improved healing and accelerated regeneration of damaged corneal nerves following LASIK. Factors that are known to support the regeneration of neurons were used as possible candidates. We also evaluated the expression of MIF following LASIK to determine its role in the regulation of infiltrating cells following LASIK, which may stimulate the release of neurotrophic factors. Methods: A corneal flap as in LASIK without the subsequent excimer laser photoablation was created on the right eye of adult New Zealand rabbits (3.5-4.5Kg. body weight). The left eye served as a control. All animals were treated according to the institutional guideline regarding animal experimentation and the ARVO regulations for the use of animals in research. Immediately following surgery the animals were randomly divided into different treatment groups (n=5 each) and received topical NGF (100 µg/ml ), NT-3 (100 ng/ml ), LIF (5 ng/ml ), NT-3+LIF, or IL-6 (5 ng/ml ) four times a day (1drop/application) for three days after surgery. Corneal nerves and their regeneration were studied in situ by confocal microscopy (NIDEK confoscan 3). Corneal sensitivity was measured with a Cochet-Bonnet aesthesiometer in normal rabbit eyes, rabbit eyes before and after LASIK and treated eyes. Real-time RT-PCR was used to determine changes in MIF mRNA expression following LASIK. Results: Neuronal growth promoting factors used in this study can induce an earlier recovery in corneal sensitivity after LASIK. Corneal sensitivity values (measured as millimeters of Cochet-Bonnet filament length) in treated animals 2 weeks postoperative was a mean of 2.54±0.66mm compared to 0.92±0.48mm of control group (p=0.0098). Confocal microscopic images disclosed sub-basal & stromal corneal nerve healing 3 weeks after LASIK in eyes treated with neurotrophic factors. MIF mRNA expression in the corneal epithelium and the infiltrating cells was upregulated three fold as determined by real-time PCR using HPRT as an internal control. Conclusions: : Our data indicate that these factors do hasten the regeneration process faster than normal conditions following LASIK and could help to overcome clinical complications such as dry eye and infections.

Keywords: cornea: tears/tear film/dry eye • animal model • laser