title: Tear film stability of protein extracts from dry eye patients administered a sigma agonist.
abstract: Fourteen dry eye volunteers placed one to two drops of 0.15% AF2975 (N,N-dimethyl-2-phenylethylamine HCl) in one eye and the vehicle in their other eye four times a day for 21 days. AF2975 is a sigma agonist known to stimulate the release of tear proteins after instillation in rabbit eyes and was tested for its ability to stabilize protein film extracted from dry eye volunteers. After day 7 and again after day 21, Schirmer test strips were inserted in each eye for 5 minutes, measured for wetting, and stored at -20 degrees C for protein analysis. A volume of 600 microliters was used to extract total protein. A portion of the extract was analyzed for total protein. The remainder was used to measure surface tension, to determine in vitro break up time (in vitro BUT) in a newly designed apparatus, and to further analyze for tear lipocalin, formerly known as presystemic tear albumin. Statistically significant differences were obtained between the drug treated eye and the vehicle treated eye for measurements determined for days 7 and 21. Tear extracts from the drug treated eye showed statistically significant decreases in surface tension and increases in in vitro BUT. Extracts from the drug treated eye also showed statistically significant increases in protein content and tear lipocalin. The results suggest that AF2975 may be able to stabilize the tear film by increasing the concentration of proteins in human tears.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Schoenwald
authors.forename: S
authors.initials: S
authors.lastname: Vidvauns
authors.forename: D E
authors.initials: DE
authors.lastname: Wurster
authors.forename: C F
authors.initials: CF
authors.lastname: Barfknecht
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D054835:Lipocalin 1; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis*; D017480:Receptors, sigma / Q000819:agonists* / Q000187:drug effects / Q000378:metabolism; D013500:Surface Tension; D013666:Tears / Q000737:chemistry*; D014985:Xerophthalmia / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D002352:Carrier Proteins; C518443:LCN1 protein, human; D054835:Lipocalin 1; D010627:Phenethylamines; D011506:Proteins; D017480:Receptors, sigma; C043554:N,N-dimethylphenylethylamine