In several ocular diseases important ocular surface pathology results from a deficiency in the secretion of lacrimal gland fluid. The long-term objective of this application is to improve treatment of aqueous tear deficiency through topical pharmacologic, and/or biomechanical means. Bromhexine may stimulate or alter the character or lacrimal gland secretion, and this project will determine the effect of bromhexine on lacrimal gland secretion in the rabbit model. Bromhexine will be administered to the lacrimal gland via the lingual artery. Lacrimal fluid flow rate, osmolarity, and protein concentration will be monitored by collecting fluid directly from the cannulated lacrimal gland excretory duct. If bromhexine is found to change any parameter of lacrimal gland fluid secretion, the mechanism of action will be studied. The effect of orally administered bromhexine will be studied over the course of several hours as well as after administration for several weeks, again by cannulating the excretory duct in anesthetized rabbits. There is good reason to expect that the ocular surface epithelium, like the corneal endothelium, has specific electrolyte and metabolite needs. These requirements would be satisfied in part by lacrimal gland fluid, but may not be satisfied by currently available medications. To optimize topical therapy, these requirements need to be defined. This project will determine the essential fluid, electrolyte, and metabolite requirements of the ocular surface epithelium normally satisfied by lacrimal gland fluid. Toxicity of potential """"""""artificial lacrimal fluid"""""""" solutions will be tested by short-term ocular bathing and chronic infusion into the intact tear film with an implantable infusion pump system. Then the long-term capability of the developed solutions to maintain epithelial health while they are infused into the tear film in the absence of lacrimal gland secretion will be investigated. Toxicity and epithelial health will be evaluated by determining corneal epithelial glycogen levels and by epithelial morphological studies.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003373-06
Application #
3257698
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1980-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02114
Gilbard, J P (1994) Human tear film electrolyte concentrations in health and dry-eye disease. Int Ophthalmol Clin 34:27-36
Gilbard, J P; Rossi, S R (1994) Changes in tear ion concentrations in dry-eye disorders. Adv Exp Med Biol 350:529-33
Gilbard, J P; Rossi, S R (1994) A unique therapeutic artificial tear formulation. Adv Exp Med Biol 350:465-9
Gilbard, J P (1994) Treatment of keratoconjunctivitis sicca in rabbits with 3-isobutyl-1-methylxanthine. Arch Ophthalmol 112:1614-6
Gilbard, J P; Rossi, S R (1992) An electrolyte-based solution that increases corneal glycogen and conjunctival goblet-cell density in a rabbit model for keratoconjunctivitis sicca. Ophthalmology 99:600-4
Gilbard, J P; Cohen, G R; Baum, J (1992) Decreased tear osmolarity and absence of the inferior marginal tear strip after sleep. Cornea 11:231-3
Gilbard, J P; Cohen, G R; Baum, J (1991) Decreased tear osmolarity and absence of the inferior marginal tear strip following sleep. Trans Am Ophthalmol Soc 89:209-13;discussion 213-4
Gilbard, J P; Rossi, S R; Heyda, K G et al. (1991) Stimulation of tear secretion and treatment of dry-eye disease with 3-isobutyl-1-methylxanthine. Arch Ophthalmol 109:672-6
Rossi, S R; Dartt, D A; Gilbard, J P (1990) Eledoisin and lacrimal secretion in the rabbit. Curr Eye Res 9:273-6
Gilbard, J P; Rossi, S R (1990) Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis. Ophthalmology 97:308-12

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