Treatment of keratoconjunctivitis sicca in rabbits with 3-isobutyl-1-methylxanthine.
OBJECTIVE
To examine the effects of topical 3-isobutyl-1-methylxanthine treatment on tear-film osmolarity, conjunctival goblet-cell densities, and corneal epithelial glycogen levels in a rabbit model for keratoconjunctivitis sicca.


METHODS
Keratoconjunctivitis sicca was surgically induced in the right eyes of 16 rabbits. In a masked protocol, eight of these operated-on eyes underwent treatment for 12 weeks with a 3.0-mmol solution of 3-isobutyl-1-methylxanthine. The remaining eight operated-on eyes were left untreated and served as controls.


RESULTS
The 3-isobutyl-1-methylxanthine treatment resulted in a rapid and significant decrease in tear osmolarity and sodium (P < .5) and potassium levels (P < .05) and a significant increase in conjunctival goblet-cell densities and corneal epithelial glycogen levels compared with untreated and operated-on controls (P < .001).


CONCLUSIONS
3-Isobutyl-1-methylxanthine rapidly and significantly decreased tear-film osmolarity in this rabbit model for keratoconjunctivitis sicca and restored conjunctival goblet-cell densities and corneal glycogen levels, thus reversing the disease process.
Gilbard
J P
JP
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Mass.
D015056:1-Methyl-3-isobutylxanthine / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology; D003315:Cornea / Q000737:chemistry / Q000187:drug effects; D006003:Glycogen / Q000032:analysis; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009994:Osmolar Concentration; D011817:Rabbits; D013666:Tears / Q000502:physiology
D006003:Glycogen; D015056:1-Methyl-3-isobutylxanthine