July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Topical Lacritin Peptides 'N-94/C-6' and 'N-94' Stabilize and Display Long Residence Time in the Tear Lipid Layer
Author Affiliations & Notes
  • Gordon W Laurie
    University of Virginia, Charlottesville, Virginia, United States
  • Jeffrey Romano
    University of Virginia, Charlottesville, Virginia, United States
  • Marc Odrich
    University of Virginia, Charlottesville, Virginia, United States
  • Denise Ryan
    Fort Belvoir, Virginia, United States
  • Kay Sia
    Fort Belvoir, Virginia, United States
  • Georgi Georgiev
    University of Sofia, Bulgaria
  • Footnotes
    Commercial Relationships   Gordon Laurie, Tearsolutions, Inc (F), TearSolutions, Inc (I), University of Virginia Licensing & Ventures Group (P); Jeffrey Romano, None; Marc Odrich, Abbott Medical Optics, Inc (C), TearSolutions, Inc (I), TearSolutions, Inc (S); Denise Ryan, None; Kay Sia, None; Georgi Georgiev, None
  • Footnotes
    Support  NIH Grants EY024327, EY026171, UVa Vivian Pinn Scholar Award, TearSolutions Inc. unrestricted gift
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4181. doi:
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      Gordon W Laurie, Jeffrey Romano, Marc Odrich, Denise Ryan, Kay Sia, Georgi Georgiev; Topical Lacritin Peptides 'N-94/C-6' and 'N-94' Stabilize and Display Long Residence Time in the Tear Lipid Layer. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4181.

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

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Purpose : Preclinical safety studies of topical, bioactive C-terminal lacritin peptide ‘N-94/C-6’ (also known as ‘LacripepTM’), and independently of the slightly longer ‘N-94’ lacritin peptide, reveal a tear residence time in rabbits of up to 24 hours. This contrasts with almost all topical ophthalmics in which residence time is limited to minutes. Interaction with the tear lipid layer can increase residence time. Here we ask whether this is indeed the case, and if so, the functional significance.

Methods : Using a computer controlled Microtrough XL with Wilhelmy wire probe, we monitored the surface pressure of human meibum film on a PBS subphase during compression and expansion recycling without or with added N-94/C-6 or N-94, or of meibum plus the glycoprotein fraction of human basal tears without or with lacritin removed by immunodepletion, or of the latter combination with added N-94/C-6 or N-94 or other synthetic peptides. Protease resistance of N-94/C-6 and N-94 for 4 hrs in tears at 37°C was assessed by matrix-associated laser desorption/ionization mass spectrometry versus protease sensitive 'SN-peptide' from laminin.

Results : N-94/C-6 or N-94 introduced in the PBS subphase quickly penetrated into the meibum film with kinetics that fitted (R2≥0.96) a sequential ‘A to B to C’ reaction model inclusive of lipid docking (‘A to B’) followed by incorporation into and subsequent stabilization of the film (‘B to C’) under increased surface pressure. Similarly, addition of tear glycoproteins, but not tear glycoproteins lacking lacritin, was stabilizing. Surface properties were best restored by supplementing tear glycoproteins lacking lacritin with N-94/C-6 or N-94, and to a somewhat lesser extent with N-terminal lacritin peptide 'C-95' and 'N-64/C-31' lacking N-94/C-6 nor N-94 sequence, and least well with an N-94/C-6 analog in which all amino acids with nonpolar side chains were substituted with serine. N-94/C-6 and N-94 are both resistant to tear proteases.

Conclusions : Long N-94/C-6 and N-94 residence time in tears is a consequence of their affinity for the tear lipid layer, whose instability in dry eye is a biophysical manifestation of ocular surface pathology. Both lacritin monomer and natural C-terminal lacritin fragments are deficient or absent in dry eye tears. Their deficiency may be in part causative for tear film instability that appears to be rescuable with N-94/C-6 or N-94.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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