Cavanagh H D, Colley A M
Center for sight, Georgetown University Medical Center Washington, DC.
Acta Ophthalmol Suppl (1985). 1989;192:115-34. doi: 10.1111/j.1755-3768.1989.tb07103.x.
Endogenous proliferation of corneal epithelial cells is regulated by a bidirectional control process characterized by an adrenergic, cAMP-dependent 'off', and a cholinergic, muscarinic cGMP-dependent 'on' response. The adrenergic receptor(s) are located in the plasma membrane (microsomal fraction), whereas the novel feature of the system is a cholinergic receptor specific for acetylcholine (ACH) located in the nuclear membrane. Exogenous substances which raise intracellular cAMP levels such as isoproterenol or PGE1, shut off epithelial mitosis: and, carbamylcholine or ACH raise intranuclear cGMP levels and increase mitosis by specific, regulatory stimulation of RNA-polymerase II activity. We believe that this regulatory system explains the transitory mitotic suppression induced by superficial corneal wounding (interruption of adrenergic fibres, chalone-effect); and the marked, permanent depression of epithelial mitosis associated with decreased intracellular ACH levels which are produced by total corneal denervation, and which results in neurotrophic keratitis.
角膜上皮细胞的内源性增殖受双向控制过程调节，其特征为肾上腺素能、cAMP依赖性的“关闭”反应和胆碱能、毒蕈碱cGMP依赖性的“开启”反应。肾上腺素能受体位于质膜（微粒体部分），而该系统的新特点是位于核膜的对乙酰胆碱（ACH）特异的胆碱能受体。诸如异丙肾上腺素或PGE1等能提高细胞内cAMP水平的外源性物质会关闭上皮细胞有丝分裂；而氨甲酰胆碱或ACH则会提高核内cGMP水平，并通过特异性调节刺激RNA聚合酶II的活性来增加有丝分裂。我们认为，该调节系统解释了浅表角膜损伤引起的短暂性有丝分裂抑制（肾上腺素能纤维中断，抑素效应）；以及与细胞内ACH水平降低相关的上皮细胞有丝分裂的显著、永久性抑制，这种降低是由角膜完全去神经支配产生的，并导致神经营养性角膜炎。
