Design and Development of an In Vitro Tear Replenishment System

Understanding the cellular and molecular mechanisms of the corneal tissue and translating them into effective therapies requires organotypic culture systems that can better model the physiological conditions of the front of the eye. Human corneal in vitro models currently exist, however, the lack of tear replenishment limits corneal in vitro models’ ability to accurately simulate the physiological environment of the human cornea. The tear replenishment system (TRS), a micro-fluidic device, was developed to mimic the in vivo tear replenishment in the human eye in an in vitro corneal model. The TRS is capable of generating adjustable intermittent flow from 0.1 µL in every cycle. The TRS is a sterilizable device that is designed to fit standard 6-well cell culture plates. Experiments with the corneal models demonstrated that exposure to the TRS did not damage the integrity of the stratified cell culture. Contact lenses “worn” by the in vitro corneal model also remained moist at all times and the cytotoxicity of BAK could also be verified using this model. These in vitro results confirmed that the TRS presents novel avenues to assess lens-solution biocompatibility and drug delivery systems in a physiologically relevant milieu.

[1]  Stephan Reichl,et al.  In vitro cell culture models to study the corneal drug absorption , 2011, Expert opinion on drug metabolism & toxicology.

[2]  Sara Williams,et al.  Development of a Curved, Stratified, In Vitro Model to Assess Ocular Biocompatibility , 2014, PloS one.

[3]  Lyndon Jones,et al.  Uptake and Release of Ciprofloxacin-HCl From Conventional and Silicone Hydrogel Contact Lens Materials , 2008, Eye & contact lens.

[4]  E. Toropainen,et al.  Cell culture models of the ocular barriers. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[5]  Alex Hui,et al.  Delivery of Ketotifen Fumarate by Commercial Contact Lens Materials , 2012, Optometry and Vision Science.

[6]  M. Gorbet,et al.  Effect of contact lens material on cytotoxicity potential of multipurpose solutions using human corneal epithelial cells , 2011, Molecular vision.

[7]  H. Lorentz,et al.  The Impact of Tear Film Components on In Vitro Lipid Uptake , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[8]  C. H. Powell,et al.  Lipophilic versus hydrodynamic modes of uptake and release by contact lenses of active entities used in multipurpose solutions. , 2010, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[9]  W Steiling,et al.  A critical review of the assessment of eye irritation potential using the draize rabbit eye test , 1998, Journal of applied toxicology : JAT.

[10]  E. Y. Zhang,et al.  Characterization of Human Corneal Epithelial Cell Model As a Surrogate for Corneal Permeability Assessment: Metabolism and Transport , 2009, Drug Metabolism and Disposition.

[11]  P. Khaw,et al.  Toxicity of natural tear substitutes in a fully defined culture model of human corneal epithelial cells. , 2001, Investigative ophthalmology & visual science.

[12]  Hiroyuki Kudo,et al.  Biomedical soft contact-lens sensor for in situ ocular biomonitoring of tear contents , 2011, Biomedical microdevices.

[13]  J. Jacob.  A – Biomaterials: Contact Lenses , 2013 .

[14]  A. Lefebvre.  Atomization and Sprays , 1988 .

[15]  W. Petroll,et al.  Corneal Epithelial Cell Viability Following Exposure to Ophthalmic Solutions Containing Preservatives and/or Antihypertensive Agents , 2012, Advances in Therapy.

[16]  L. Keay,et al.  Epidemiology of Contact Lens–Related Inflammation and Microbial Keratitis: A 20-year Perspective , 2007, Eye & contact lens.

[17]  C. Baudouin,et al.  Multiple endpoint analysis of the 3D-reconstituted corneal epithelium after treatment with benzalkonium chloride: early detection of toxic damage. , 2009, Investigative ophthalmology & visual science.

[18]  A. Mitra,et al.  Ophthalmic Drug Delivery Systems , 2003 .

[19]  L. Keay,et al.  Multicenter Case-Control Study of the Role of Lens Materials and Care Products on the Development of Corneal Infiltrates , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[20]  Nadia Dami,et al.  Eye irritation of low-irritant cosmetic formulations: correlation of in vitro results with clinical data and product composition. , 2005, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[21]  Robert N Weinreb,et al.  Continuous 24-hour monitoring of intraocular pressure patterns with a contact lens sensor: safety, tolerability, and reproducibility in patients with glaucoma. , 2012, Archives of ophthalmology.

[22]  F. Castro‐Muñozledo.  Corneal epithelial cell cultures as a tool for research, drug screening and testing. , 2008, Experimental eye research.

[23]  S. Klyce,et al.  Determination of tear volume and tear flow. , 1966, Investigative ophthalmology.

[24]  C. Baudouin,et al.  Preservatives in eyedrops: The good, the bad and the ugly , 2010, Progress in Retinal and Eye Research.

[25]  B. Sjöquist,et al.  Ocular and systemic pharmacokinetics of latanoprost in humans. , 2002, Survey of ophthalmology.

[26]  J. Ubels,et al.  Cytotoxicity Testing of Multipurpose Contact Lens Solutions Using Monolayer and Stratified Cultures of Human Corneal Epithelial Cells , 2009, Eye & contact lens.

[27]  S. Klyce.  Electrical profiles in the corneal epithelium , 1972, The Journal of physiology.

[28]  Huanfen Yao,et al.  A contact lens with embedded sensor for monitoring tear glucose level. , 2011, Biosensors & bioelectronics.

[29]  R. Villa,et al.  Prototype of a nanostructured sensing contact lens for noninvasive intraocular pressure monitoring. , 2011, Investigative ophthalmology & visual science.

[30]  J. Tiffany,et al.  Tear film stability and tear surface tension. , 1989, Current eye research.

[31]  H. Sheardown,et al.  Corneal epithelial cell biocompatibility to silicone hydrogel and conventional hydrogel contact lens packaging solutions , 2010, Molecular vision.

[32]  Magne Helland,et al.  Twenty first century trends in silicone hydrogel contact lens fitting: an international perspective. , 2010, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[33]  David M Lehmann,et al.  Impact of assay selection and study design on the outcome of cytotoxicity testing of medical devices: the case of multi-purpose vision care solutions. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[34]  Meredith E. Jansen,et al.  Age and other risk factors for corneal infiltrative and inflammatory events in young soft contact lens wearers from the Contact Lens Assessment in Youth (CLAY) study. , 2011, Investigative ophthalmology & visual science.

[35]  S Reichl,et al.  Human corneal equivalent as cell culture model for in vitro drug permeation studies , 2004, British Journal of Ophthalmology.

[36]  M. Mowrey-Mckee,et al.  Comparative cytotoxicity potential of soft contact lens care regimens. , 2001, The CLAO journal : official publication of the Contact Lens Association of Ophthalmologists, Inc.

[37]  K. Ward,et al.  Effect of a novel multipurpose contact lens solution on human corneal epithelial barrier function. , 2010, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[38]  K. Ward,et al.  In vitro biocompatibility assessment of multipurpose contact lens solutions: effects on human corneal epithelial viability and barrier function. , 2012, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[39]  Justin T. Baca,et al.  Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. , 2007, The ocular surface.

[40]  J. Tiffany.  The viscosity of human tears , 1991, International Ophthalmology.