June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Topical application of a novel Harderian-derived nonpolar lipid prolongs tear film break up time in normal Beagle dogs
Author Affiliations & Notes
  • Brian C Leonard
    VM: Surgical and Radiological Sciences, University of California Davis, Davis, California, United States
  • Sangwan Park
    VM: Surgical and Radiological Sciences, University of California Davis, Davis, California, United States
  • Daniel M Albert
    Oregon Health & Science University, Portland, Oregon, United States
    MCAL Therapeutics, California, United States
  • Charles A. O’Neill
    MCAL Therapeutics, California, United States
  • Thomas R. Gadek
    MCAL Therapeutics, California, United States
  • Atul N. Parikh
    Department of Biomedical Engineering, University of California Davis, Davis, California, United States
  • Footnotes
    Commercial Relationships   Brian Leonard MCAL Therapeutics, Code F (Financial Support); Sangwan Park None; Daniel Albert MCAL Therapeutics, Code S (non-remunerative); Charles O’Neill MCAL Therapeutics, Code S (non-remunerative); Thomas Gadek MCAL Therapeutics, Code S (non-remunerative); Atul Parikh None
  • Footnotes
    Support  K08EY028199
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3986 – A0266. doi:
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    • Get Citation

      Brian C Leonard, Sangwan Park, Daniel M Albert, Charles A. O’Neill, Thomas R. Gadek, Atul N. Parikh; Topical application of a novel Harderian-derived nonpolar lipid prolongs tear film break up time in normal Beagle dogs. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3986 – A0266.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Dry eye disease (DED) is a common ophthalmic condition with many underlying causes that are unified by the destabilization of the tear film. Despite current therapeutics, many patients with DED require additional treatments to provide comfort and reduce irritation. We recently identified a novel nonpolar lipid (NPL) isolated from the Harderian gland of the rabbit, not found in human meibum or tears, that increased tear film break up time (TFBUT) and improved ocular surface health in a rabbit model of DED. The purpose of this study was to determine the effect of this novel NPL on TFBUT in normal Beagle dogs.

Methods : In phase 1, a pilot study was performed to determine the dose of the rabbit NPL that prolonged TFBUT from baseline. Dogs (n = 2) were treated with a single dose of NPL (vehicle, 0.1, 0.5, 1, 3 and 10 mg/mL) in both eyes and TFBUT was measured at 1, 3, 6, 12 and 24 hours (h) post-treatment. In phase 2, dogs (n = 5) received one of three treatments (vehicle, 1 mg/mL or 3 mg/mL NPL) once in both eyes and TFBUT was measured at 6 and 24 h post-treatment. In phase 3, dogs (n = 3) received multiple doses (3 mg/mL NPL) over four days and TFBUT was performed at 6 and 80 h post-treatment. Semi-quantitative preclinical ocular toxicology scoring (SPOTS) was performed to document adverse events.

Results : In phase 1, topical treatment with NPL resulted in a dose-dependent increase in TFBUT in healthy Beagle dogs with the most optimal concentration of 3 mg/mL (mean change from baseline [MCB]: 1 h, +9.6 seconds [s]; 3 h, +8.1 s; 6 h, +3.4 s; 12 h, +3.0 s; 24 h, +7.7 s). In phase 2, topical treatment with NPL resulted in an increase in TFBUT with the 1 mg/mL dose (MCB: 6 h, +3.4 s; 24 h, 2.1 s) yet more pronounced increase in MCB TFBUT with the 3 mg/mL dose (6 h, +4.48 s; 24 h, +3.86 s). In phase 3, there was an increase in TFBUT measured at 6 h post-treatment with NPL (6 h, +3.3 s) that returned to baseline levels at 80 h post-treatment (80 h, +0.1 s). The topical NPL was well-tolerated with no pathologic changes detected using the SPOTS system.

Conclusions : Overall, treatment with a single dose of the NPL was well-tolerated at all doses tested and resulted in an increased TFBUT MCB that was most pronounced with the 3 mg/mL dose. Future studies will be focused on determining the effect of this NPL on stabilizing the tear film in murine and canine models of DED.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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