Abstract
Purpose: :
Laser in situ keratomileusis (LASIK) refractive surgery has been well accepted for treatment of myopia. However, creation of the corneal flap causes nerve degeneration and decreases corneal sensitivity, leading to dry eye and neurotrophic epitheliopathy. Our previous study showed that somatostatin accelerated recovery of corneal sensitivity in a rabbit model of LASIK surgery. FK962 is an enhancer of somatostatin release, and it improved memory deficits in animal models. The purpose of the present experiment was to test if FK962 facilitates axonal elongation and recovery of corneal sensitivity after creation of a corneal flap in rabbits.
Methods: :
One 130 µm-thick by 8.5 mm-diameter flap was created on each rabbit cornea, and 1 µM FK962 was applied topically 4 times per day. Clinical studies previously found that decreased corneal sensitivity and concomitant complications were usually observed one week after surgery. Corneal sensitivity in rabbits was thus measured 8 days after flap creation using Cochet-Bonnet esthesiometer. Whole-mount corneal sections were prepared and immunolabeled with anti-neurofilament antibody to visualize transected nerves. The elongated axons from the transected nerve terminal were scored to assess re-innervation. Rabbit trigeminal ganglion cells were also cultured for 48 hours with FK962 to confirm axonal elongation in vitro.
Results: :
In control animals, distal axons from transected nerve terminals disappeared soon after flap surgery, and with time, axons then regenerated and elongated. Increasing corneal sensitivity was well associated with axonal elongation suggesting functional re-innervation. Topical application of FK962 for 7 days significantly enhanced elongation of axons toward corneal sub-epithelial region compared to controls. Corneal sensitivity was also significantly enhanced by FK962. FK962 also significantly increased sprouting and elongation of axons in cultured trigeminal ganglion cells.
Conclusions: :
The results from our rabbit model showed that topical application of FK962 facilitated corneal re-innervation and recovery of sensitivity. We speculate that topical application of FK962 may decrease complications in patients after LASIK surgery.
Keywords: innervation: sensation • drug toxicity/drug effects • refractive surgery: LASIK