The molecular basis of neurotrophic keratitis.
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.
Cavanagh
H D
HD
Center for sight, Georgetown University Medical Center Washington, DC.
Colley
A M
AM
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004728:Endothelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D007634:Keratitis / Q000209:etiology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008938:Mitosis / Q000187:drug effects; D008958:Models, Molecular; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010277:Parasympathomimetics / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction; D013566:Sympathomimetics / Q000494:pharmacology
D009712:Nucleotides, Cyclic; D010277:Parasympathomimetics; D011458:Prostaglandins E; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D013566:Sympathomimetics; D011494:Protein Kinases; D012321:DNA-Directed RNA Polymerases; D004259:DNA-Directed DNA Polymerase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases