Analysis of nueroparalytic keratitics using coculture system of neural and corneal epithelial cells

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With the use of a coculture system based on a collagen vitrigel membrane, we have investigated the effects of neural cells on human corneal epithelial (HCE) cells. We found that the presence of neural cells promoted the stratification of HCE cells as well as up-regulated expression of the junction protein N-cadherin. These effects of neural cells were mimicked by conditioned medium prepared from differentiating PC12 cells or by neuropeptides (substance P and CGRP) released from trigeminal nerve cells. Furthermore, antagonists of these neuropeptides inhibited the stimulatory effects of trigeminal neurons on the stratification of and N-cadherin expression by HCE cells. Our results thus indicate that neuropeptides released from trigeminal neurons up-regulate N-cadherin expression in and promote the stratification of corneal epithelial cells, and they therefore suggest that such neurons may play an important role in the maintenance of corneal homeostasis and repair of corneal damage.