SYMPATHETIC-STIMULATION OF CORNEAL EPITHELIAL PROLIFERATION IN WOUNDED AND NONWOUNDED RAT EYES

Purpose. To determine the effect of ocular sympathetic nerves on corne al epithelial proliferation in the rat. Methods. Osmotic pumps filled with bromodeoxyuridine (BrdU) were implanted subcutaneously in adult r ats to label corneal epithelial cells entering the S-phase of the cell cycle during a 24-hour period. Corneas in some animals were wounded w ith n-heptanol. Several days or weeks before pump implantation, animal s were subjected to either unilateral superior cervical ganglionectomy (SCGectomy), unilateral transection of the cervical sympathetic trunk (sympathetic decentralization), bilateral SCGectomy plus unilateral t opical norepinephrine administration, or unilateral SCGectomy plus sys temic capsaicin administration. Differences in BrdU-labeling indices b etween experimental and control eyes in each group were determined fro m cell counts on paraffin sections. Results. Superior cervical ganglio nectomy and sympathetic decentralization significantly decreased epith elial proliferation in nonwounded and wounded corneas. Topical applica tions of norepinephrine to eyes that had been deprived of their sympat hetic innervation completely reversed the antiproliferative effect of ocular sympathectomy. Systemic administration of the neurotoxin capsai cin, in conjunction with unilateral SCGectomy, did not alter the proli ferative 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 t hese nerves occurs independently of functional interactions with capsa icin-sensitive, ocular sensory nerves and appears to be related, at le ast in part, to the release of norepinephrine.