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.

Conjunctival vaccination against Brucella ovis in mice with mannosylated nanoparticles

“…The drainage of the administered dose via the nasolachrymal system takes place when the volume of fluid in the eye exceeds the normal lachrymal volume. More important, the lachrymation and the physiological tear turnover are stimulated by the instillation of even mildly irritating fluids compromising bioavailability [28,29]. Under these circumstances it appears that the induction of immune responses through instillation of a vaccine in the eye would be an important challenge.…”

Decreased tear lipocalin concentration in patients with meibomian gland dysfunction

“…7 This protective function of TL may be compromised in dry eye syndrome. 9 Meibomian gland dysfunction (MGD), a common, chronic condition of the posterior eyelids, comprises a significant part of dry eye syndrome. [10][11][12] The lipid layer, the outermost layer of the tear film produced by the meibomian glands, stabilises tear films by retarding evaporation and lowering surface tension.…”

Tear Lipocalin: Evidence for a Scavenging Function to Remove Lipids from the Human Corneal Surface

“…30 Furthermore, the concentration of TL correlates with tear film stability. 31 In dry eye disease the tear film is thin, and the cornea is readily exposed to lipid contamination. 5,6 The precise nature of the interaction of lipids with molecules at the corneal surface remains to be explored.…”