Sympathetic stimulation of corneal epithelial proliferation in wounded and nonwounded rat eyes.

Purpose: To determine the effect of ocular sympathetic nerves on corneal epithelial proliferation in the rat.

Methods: Osmotic pumps filled with bromodeoxyuridine (BrdU) were implanted subcutaneously in adult rats to label corneal epithelial cells entering the S-phase of the cell cycle during a 24-hour period. Corneas in some animals were wounded with n-heptanol. Several days or weeks before pump implantation, animals were subjected to either unilateral superior cervical ganglionectomy (SCGectomy), unilateral transection of the cervical sympathetic trunk (sympathetic decentralization), bilateral SCGectomy plus unilateral topical norepinephrine administration, or unilateral SCGectomy plus systemic capsaicin administration. Differences in BrdU-labeling indices between experimental and control eyes in each group were determined from cell counts on paraffin sections.

Results: Superior cervical ganglionectomy and sympathetic decentralization significantly decreased epithelial proliferation in nonwounded and wounded corneas. Topical applications of norepinephrine to eyes that had been deprived of their sympathetic innervation completely reversed the antiproliferative effect of ocular sympathectomy. Systemic administration of the neurotoxin capsaicin, in conjunction with unilateral SCGectomy, did not alter the proliferative rate; comparison was made to animals that received unilateral SCGectomy only.

Conclusions: Ocular sympathetic nerves stimulate rat corneal epithelial proliferation under normal physiological conditions and during corneal wound healing. The promotion of DNA synthesis by these nerves occurs independently of functional interactions with capsaicin-sensitive, ocular sensory nerves and appears to be related, at least in part, to the release of norepinephrine.