Evaluation of novel dry eye model: preganglionic parasympathetic denervation in rabbit.

PURPOSE To evaluate ocular surface status after interruption of preganglionic, parasympathetic neural control after surgical removal of the greater superficial petrosal nerve (GSPN). METHODS New Zealand White rabbits underwent unilateral section and removal of a 5-mm portion of the GSPN by a route through the inner ear; no ocular or orbital tissue was involved. Before and 7 days after surgery, all animals underwent preliminary examination, including fluorescein staining, rose bengal instillation, blink rate, tear breakup time (BUT), tear flow, and impression cytology. Total tarsorrhaphy was carried out in four additional rabbits, and another four animals underwent unilateral sham procedures. The GSPN, pterygopalatine ganglion, lacrimal gland, and conjunctiva were evaluated by light and transmission electron microscopy (TEM). RESULTS GSPN sectioning resulted in significant changes of the ocular surface after 7 days: intense rose bengal staining of the conjunctiva, fluorescein staining of the cornea, increased blink rate (P < 0.05), decreased BUT (P < 0.005), decreased tear flow by 26% (P < 0.005), and decreased goblet cell density (P < 0.01). TEM revealed massive accumulation of secretory granules in lacrimal acinar cells. The changes were also seen after tarsorrhaphy. Neither the contralateral control nor the sham eyes were affected. CONCLUSIONS The effects of GSPN nerve section led to the rapid onset of a dry eye condition in the rabbits that continued for at least 1 week. The authors suggest that continuous neural drive of the pterygopalatine ganglion is necessary to maintain adequate tear flow and mucin secretion. It is likely the trigeminal system is the afferent origin of this continuous neural tone.

[1]  R. Beuerman,et al.  The Lacrimal Functional Unit , 2004 .

[2]  R. Beuerman,et al.  Dry eye and ocular surface disorders , 2004 .

[3]  R. Beuerman,et al.  The role of the lacrimal functional unit in the pathophysiology of dry eye. , 2004, Experimental eye research.

[4]  J. Milbrandt,et al.  Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca. , 2003, Investigative ophthalmology & visual science.

[5]  D. Dartt Regulation of mucin and fluid secretion by conjunctival epithelial cells , 2002, Progress in Retinal and Eye Research.

[6]  T. Hamano,et al.  Effect of Gefarnate on the Ocular Surface in Squirrel Monkeys , 2002, Cornea.

[7]  J. Nelson Diagnosis and treatment of the dry eye: a clinical perspective. , 2000, Advances in experimental medicine and biology.

[8]  N. Toda,et al.  Preganglionic and Postganglionic Neurons Responsible for Cerebral Vasodilation Mediated by Nitric Oxide in Anesthetized Dogs , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  R. Beuerman,et al.  Tear production after unilateral removal of the main lacrimal gland in squirrel monkeys. , 2000, Archives of ophthalmology.

[10]  M. Palkovits,et al.  Lacrimal preganglionic neurons form a subdivision of the superior salivatory nucleus of rat: transneuronal labelling by pseudorabies virus. , 1999, Journal of the autonomic nervous system.

[11]  J. Zieske,et al.  Immunolocalization of muscarinic and VIP receptor subtypes and their role in stimulating goblet cell secretion. , 1999, Investigative ophthalmology & visual science.

[12]  S. Burgalassi,et al.  Development of a Simple Dry Eye Model in the Albino Rabbit and Evaluation of Some Tear Substitutes , 1999, Ophthalmic Research.

[13]  M. Saarma,et al.  Retarded Growth and Deficits in the Enteric and Parasympathetic Nervous System in Mice Lacking GFRα2, a Functional Neurturin Receptor , 1999, Neuron.

[14]  M. Gallagher,et al.  Evaluation of Muscarinic M2 Receptor Sites in Basal Forebrain and Brainstem Cholinergic Systems of Behaviorally Characterized Young and Aged Long-Evans Rats , 1998, Neurobiology of Aging.

[15]  R. Beuerman,et al.  Effect of Sensory Denervation on the Structure and Physiologic Responsiveness of Rabbit Lacrimal Gland , 1998, Cornea.

[16]  M. Tamai,et al.  Correlation between vasodilatation and secretion in the lacrimal gland elicited by stimulation of the cornea and facial nerve root of the cat. , 1997, Investigative ophthalmology & visual science.

[17]  K. Nakamori,et al.  Blinking is controlled primarily by ocular surface conditions. , 1997, American journal of ophthalmology.

[18]  B. Baljet,et al.  Innervation of the lacrimal gland in the cynomolgous monkey: a retrograde tracing study. , 1996, Journal of anatomy.

[19]  R. Beuerman,et al.  Ultrastructure of the human cornea , 1996, Microscopy research and technique.

[20]  J. Craig,et al.  Tear lipid layer structure and stability following expression of the meibomian glands. , 1995, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[21]  K. Sharkey,et al.  Innervation and mast cells of the rat exorbital lacrimal gland: the effects of age. , 1994, Journal of the autonomic nervous system.

[22]  P. Seifert,et al.  The architecture of human accessory lacrimal glands. , 1993, German journal of ophthalmology.

[23]  K. Tsubota,et al.  Practical double vital staining for ocular surface evaluation. , 1993, Cornea.

[24]  Leo J. Maguire Noninvasive Diagnostic Techniques in Ophthalmology , 1991 .

[25]  J. Klooster,et al.  Pre- and post-ganglionic nerve fibres of the pterygopalatine ganglion and their allocation to the eyeball of rats , 1990, Brain Research.

[26]  P. Goadsby,et al.  Sphenopalatine ganglion stimulation increases regional cerebral blood flow independent of glucose utilization in the cat , 1990, Brain Research.

[27]  J. P. Gilbard,et al.  Natural history of disease in a rabbit model for keratoconjunctivitis sicca , 1989, Acta ophthalmologica. Supplement.

[28]  J. P. Gilbard,et al.  A new rabbit model for keratoconjunctivitis sicca. , 1987, Investigative ophthalmology & visual science.

[29]  N. V. van Haeringen,et al.  Comparison of tears and lacrimal gland fluid in the rabbit and guinea pig. , 1985, Current eye research.

[30]  J. M. Butler,et al.  Effects of VIIth (facial) nerve degeneration on vasoactive intestinal polypeptide and substance P levels in ocular and orbital tissues of the rabbit. , 1984, Experimental eye research.

[31]  B. Schimmelpfennig,et al.  Sensory denervation of the rabbit cornea affects epithelial properties , 1980, Experimental Neurology.

[32]  D. Maurice,et al.  A simple conjunctival biopsy. , 1977, American journal of ophthalmology.

[33]  G. Ruskell The distribution of autonomic post-ganglionic nerve fibres to the lacrimal gland in monkeys. , 1971, Journal of anatomy.

[34]  Ruskell Gl The orbital branches of the pterygopalatine ganglion and their relationship with internal carotid nerve branches in primates. , 1970 .

[35]  O. P. Bijsterveld,et al.  Diagnostic Tests in the Sicca Syndrome , 1969 .

[36]  A. M. Goldstein,et al.  Inhibition and facilitation of pilocarpine-induced lacrimal flow by norepinephrine. , 1967, Investigative ophthalmology.

[37]  J. Whitwell DENERVATION OF THE LACRIMAL GLAND* , 1958, The British journal of ophthalmology.

[38]  G. F. Rowbotham OBSERVATIONS ON THE EFFECTS OF TRIGEMINAL DENERVATION , 1939 .

[39]  S. Ruskin CONTROL OF TEARING BY BLOCKING THE NASAL GANGLION , 1930 .

[40]  G. Ruskell Changes in nerve terminals and acini of the lacrimal gland and changes in secretion induced by autonomic denervation , 2004, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[41]  A. Konno,et al.  An electrophysiological study of pterygopalatine ganglion neurons in the rabbit. , 1998, Acta oto-laryngologica. Supplementum.

[42]  R. Beuerman,et al.  Effects of lacrimal gland removal on squirrel monkey cornea. , 1998, Advances in experimental medicine and biology.

[43]  D. Maurice The effect of the low blink rate in rabbits on topical drug penetration. , 1995, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[44]  J. Zieske,et al.  Localization of nerves adjacent to goblet cells in rat conjunctiva. , 1995, Current eye research.

[45]  M. Nakamura,et al.  Establishment of a rabbit short-term dry eye model. , 1995, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[46]  D. Dartt,et al.  Neural stimulation of conjunctival goblet cell mucous secretion in rats. , 1994, Advances in experimental medicine and biology.

[47]  D. Dartt Regulation of tear secretion. , 1994, Advances in experimental medicine and biology.

[48]  D. Jabs,et al.  Murine models of Sjögren's syndrome. , 1994, Advances in experimental medicine and biology.

[49]  R. Beuerman,et al.  Evaluation of Corneal Sensitivity , 1990 .

[50]  M. Sanders,et al.  Ocular autonomic nerve function in Lambert-Eaton myasthenic syndrome , 1990, Eye.

[51]  J. Baum Clinical manifestations of dry eye states. , 1985, Transactions of the ophthalmological societies of the United Kingdom.

[52]  W. Chapman,et al.  Keratoconjunctivitis sicca: histopathologic study of nictitating membrane and lacrimal glands from 28 dogs. , 1984, American journal of veterinary research.

[53]  G. Ruskell The orbital branches of the pterygopalatine ganglion and their relationship with internal carotid nerve branches in primates. , 1970, Journal of anatomy.

[54]  O. P. van Bijsterveld Diagnostic tests in the Sicca syndrome. , 1969, Archives of ophthalmology.

[55]  K. Wybar,et al.  The anatomy of the visual system , 1961 .

[56]  E. D. de Haas Lacrimal gland response to parasympathicomimetics after parasympathetic denervation. , 1960, Archives of ophthalmology.