Evaluation of a Novel Artificial Tear in the Prevention and Treatment of Dry Eye in an Animal Model

Yujing She, Jinyang Li, Bing Xiao, Huihui Lu, Haixia Liu, Peter A Simmons, Joseph G Vehige, Wei Chen, Yujing She, Jinyang Li, Bing Xiao, Huihui Lu, Haixia Liu, Peter A Simmons, Joseph G Vehige, Wei Chen

Abstract

Purpose: To evaluate effects of a novel multi-ingredient artificial tear formulation containing carboxymethylcellulose (CMC) and hyaluronic acid (HA) in a murine dry eye model.

Methods: Dry eye was induced in mice (C57BL/6) using an intelligently controlled environmental system (ICES). CMC+HA (Optive Fusion™), CMC-only (Refresh Tears(®)), and HA-only (Hycosan(®)) artificial tears and control phosphate-buffered saline (PBS) were administered 4 times daily and compared with no treatment (n = 64 eyes per group). During regimen 1 (prevention regimen), mice were administered artificial tears or PBS for 14 days (starting day 0) while they were exposed to ICES, and assessed on days 0 and 14. During regimen 2 (treatment regimen), mice exposed to ICES for 14 days with no intervention were administered artificial tears or PBS for 14 days (starting day 14) while continuing exposure to ICES, and assessed on days 0, 14, and 28. Corneal fluorescein staining and conjunctival goblet cell density were measured.

Results: Artificial tear-treated mice had significantly better outcomes than control groups on corneal staining and goblet cell density (P < 0.01). Mice administered CMC+HA also showed significantly lower corneal fluorescein staining and higher goblet cell density, compared with CMC (P < 0.01) and HA (P < 0.05) in both regimens 1 and 2.

Conclusions: The artificial tear formulation containing CMC and HA was effective in preventing and treating environmentally induced dry eye. Improvements observed for corneal fluorescein staining and conjunctival goblet cell retention suggest that this combination may be a viable treatment option for dry eye disease.

Figures

FIG. 1.
FIG. 1.
Representative corneal fluorescein staining in mice assessed on day 14 (regimen 1) and day 28 (regimen 2) after placement in the ICES dry eye chamber and treatment with topical artificial tear formulations. CMC, carboxymethylcellulose; HA, hyaluronic acid; ICES, intelligently controlled environmental system; PBS, phosphate-buffered saline; NT, no treatment.
FIG. 2.
FIG. 2.
Mean corneal fluorescein staining in mice (64 eyes, n = 32) housed in the ICES chamber. (a) Regimen 1: artificial tear formulations were administered to mice immediately after placement in the ICES dry eye chamber, and corneal staining was evaluated at days 0 and 14. (b) Regimen 2: artificial tear formulations were administered to mice after 14 days of initiating ICES-induced dry eye, and corneal staining was evaluated at days 0, 14, and 28 after continued exposure to the ICES chamber. Arrows indicate when administration of artificial tears was initiated for mice treated in regimen 1 and regimen 2. *P < 0.01; **P < 0.05 between treatment groups compared on the same day.
FIG. 3.
FIG. 3.
Representative periodic acid–Schiff staining of conjunctival goblet cells on day 14 (regimen 1) and day 28 (regimen 2) of exposure to the ICES dry eye chamber and treatment with topical artificial tear formulations. Magnification, 40×; scale bars, 20 μm.
FIG. 4.
FIG. 4.
Mean number of conjunctival goblet cells in mice (12 eyes, n = 6) housed in the ICES chamber. (a) Regimen 1: artificial tear formulations were administered to mice immediately after placement in the ICES dry eye chamber and goblet cells were quantified at day 14. (b) Regimen 2: artificial tear formulations were administered to mice after 14 days of exposure to the ICES dry eye chamber and goblet cells were quantified at day 28 after continued exposure to the ICES chamber. *P < 0.01; **P < 0.05 between treatment groups compared on the same day.

References

    1. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. Ocul. Surf. 5:75–92, 2007
    1. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop. Ocul. Surf. 5:93–107, 2007
    1. Song X.J., Li D.Q., Farley W., et al. . Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca. Invest. Ophthalmol. Vis. Sci. 44:4223–4229, 2003
    1. Baudouin C., Haouat N., Brignole F., Bayle J., and Gastaud P. Immunopathological findings in conjunctival cells using immunofluorescence staining of impression cytology specimens. Br. J. Ophthalmol. 76:545–549, 1992
    1. Behrens A., Doyle J.J., Stern L., et al. . Dysfunctional Tear Syndrome Study Group. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 25:900–907, 2006
    1. Grene R.B., Lankston P., Mordaunt J., et al. . Unpreserved carboxymethylcellulose artificial tears evaluated in patients with keratoconjunctivitis sicca. Cornea. 11:294–301, 1992
    1. Simmons P.A., and Vehige J.G. Clinical performance of a mid-viscosity artificial tear for dry eye treatment. Cornea. 26:294–302, 2007
    1. Simmons P.A., Beard B.J., and Vehige J.G. Optimizing viscosity of ophthalmic solutions with the combination of two polymers. Presented at the 7th International Conference on the Tear Film & Ocular Surface: Basic Science and Clinical Relevance; September 18–21, 2013; Taormina, Italy
    1. Schrader S., Mircheff A.K., and Geerling G. Animal models of dry eye. Dev. Ophthalmol. 41:298–312, 2008
    1. Chen W., Zhang X., Zhang J., et al. . A murine model of dry eye induced by an intelligently controlled environmental system. Invest. Ophthalmol. Vis. Sci. 49:1386–1391, 2008
    1. Barabino S., Shen L., Chen L., et al. . The controlled-environment chamber: a new mouse model of dry eye. Invest. Ophthalmol. Vis. Sci. 46:2766–2771, 2005
    1. Chen W., Zhang X., Liu M., et al. . Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis. Exp. Eye Res. 89:311–318, 2009
    1. Li J., Roubeix C., Wang Y., et al. . Therapeutic efficacy of trehalose eye drops for treatment of murine dry eye induced by an intelligently controlled environmental system. Mol. Vis. 18:317–329, 2012
    1. Chen W., Zhang X., Li J., et al. . Efficacy of osmoprotectants on prevention and treatment of murine dry eye. Invest. Ophthalmol. Vis. Sci. 54:6287–6897, 2013
    1. Zheng Q., Ren Y., Reinach P.S., et al. . Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye. Exp. Eye Res. 125:1–8, 2014
    1. Baudouin C. [A new approach for better comprehension of diseases of the ocular surface]. J. Fr. Ophtalmol. 30:239–246, 2007
    1. Aragona P., Papa V., Micali A., Santocono M., and Milazzo G. Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye. Br. J. Ophthalmol. 86:181–184, 2002
    1. Doughty M.J., and Glavin S. Efficacy of different dry eye treatments with artificial tears or ocular lubricants: a systematic review. Ophthalmic Physiol. Opt. 29:573–583, 2009
    1. Lee J.H., Ahn H.S., Kim E.K., and Kim T.-I. Efficacy of sodium hyaluronate and carboxymethylcellulose in treating mild to moderate dry eye disease. Cornea. 30:175–179, 2011
    1. Garrett Q., Simmons P.A., Xu S., et al. . Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of corneal epithelial wound healing. Invest. Ophthalmol. Vis. Sci. 48:1559–1567, 2007
    1. Garrett Q., Xu S., Simmons P.A., et al. . Carboxymethyl cellulose stimulates rabbit corneal epithelial wound healing. Curr. Eye Res. 33:567–573, 2008
    1. Gomes J.A., Amankwah R., Powell-Richards A., and Dua H.S. Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. Br. J. Ophthalmol. 88:821–825, 2004
    1. Vogel R., Crockett R.S., Oden N., Laliberte T.W., Molina L.; Sodium Hyaluronate Ophthalmic Solution Study Group. Demonstration of efficacy in the treatment of dry eye disease with 0.18% sodium hyaluronate ophthalmic solution (Vismed, Rejena). Am. J. Ophthalmol. 149:594–601, 2010
    1. Baeyens V., Bron A., Baudouin C.; Vismed/Hylovis Study Group. Efficacy of 0.18% hypotonic sodium hyaluronate ophthalmic solution in the treatment of signs and symptoms of dry eye disease. J. Fr. Ophtalmol. 35:412–419, 2012
    1. Baudouin C., Cochener B., Pisella P.J., et al. . Randomized, phase III study comparing osmoprotective carboxymethylcellulose with sodium hyaluronate in dry eye disease. Eur. J. Ophthalmol. 22:751–761, 2012
    1. Paugh J.R., Nguyen A.L., Ketelson H.A., Christensen M.T., and Meadows D.L. Precorneal residence time of artificial tears measured in dry eye subjects. Optom. Vis. Sci. 85:725–731, 2008
    1. Simmons P.A., Liu H., Carlisle-Wilcox C., Shi G., and Vehige J.G. A multi-center, double-masked, randomized study to compare the safety, efficacy, and acceptability of two investigational eye drop formulations to cellufluid for three months in subjects with dry eye disease. Presented at the 4th EuCornea Congress; October4–5, 2013; Amsterdam RAI, the Netherlands

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