Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 10 December 1999:
Vol. 286. no. 5447, pp. 2169 - 2172
DOI: 10.1126/science.286.5447.2169

Reports

Functional Human Corneal Equivalents Constructed from Cell Lines

May Griffith, 1* Rosemarie Osborne, 2 Rejean Munger, 1 Xiaojuan Xiong, 1 Charles J. Doillon, 3 Noelani L. C. Laycock, 1 Malik Hakim, 1 Ying Song, 1 Mitchell A. Watsky 4

Human corneal equivalents comprising the three main layers of the cornea (epithelium, stroma, and endothelium) were constructed. Each cellular layer was fabricated from immortalized human corneal cells that were screened for use on the basis of morphological, biochemical, and electrophysiological similarity to their natural counterparts. The resulting corneal equivalents mimicked human corneas in key physical and physiological functions, including morphology, biochemical marker expression, transparency, ion and fluid transport, and gene expression. Morphological and functional equivalents to human corneas that can be produced in vitro have immediate applications in toxicity and drug efficacy testing, and form the basis for future development of implantable tissues.

1 University of Ottawa Eye Institute and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa Hospital-General Campus, Ottawa, Ontario K1H 8L6, Canada.
2 Human & Environmental Safety Division, Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45253, USA.
3 Biomaterials Institute of Quebec, Pavillon St. Francois d'Assise, Centre Hospitalier et Universitaire de Quebec, Quebec G1L 3L5, Canada.
4 Department of Physiology, University of Tennessee College of Medicine, Memphis, TN 38163, USA.
*   To whom correspondence should be addressed. E-mail: mgriffith{at}ogh.on.ca


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
NC-1059: A Channel-Forming Peptide That Modulates Drug Delivery across In Vitro Corneal Epithelium.
J. Martin, P. Malreddy, T. Iwamoto, L. C. Freeman, H. J. Davidson, J. M. Tomich, and B. D. Schultz (2009)
Invest. Ophthalmol. Vis. Sci. 50, 3337-3345
   Abstract »    Full Text »    PDF »
Transplantation of a Tissue-Engineered Corneal Endothelium Reconstructed on a Devitalized Carrier in the Feline Model.
S. Proulx, T. Bensaoula, O. Nada, C. Audet, J. d'Arc Uwamaliya, A. Devaux, G. Allaire, L. Germain, and I. Brunette (2009)
Invest. Ophthalmol. Vis. Sci. 50, 2686-2694
   Abstract »    Full Text »    PDF »
Impact of Cell Source on Human Cornea Reconstructed by Tissue Engineering.
P. Carrier, A. Deschambeault, C. Audet, M. Talbot, R. Gauvin, C. J. Giasson, F. A. Auger, S. L. Guerin, and L. Germain (2009)
Invest. Ophthalmol. Vis. Sci. 50, 2645-2652
   Abstract »    Full Text »    PDF »
Genomic Aberrations and Cellular Heterogeneity in SV40-Immortalized Human Corneal Epithelial Cells.
K. Yamasaki, S. Kawasaki, R. D. Young, H. Fukuoka, H. Tanioka, M. Nakatsukasa, A. J. Quantock, and S. Kinoshita (2009)
Invest. Ophthalmol. Vis. Sci. 50, 604-613
   Abstract »    Full Text »    PDF »
Development of a Reconstructed Cornea from Collagen-Chondroitin Sulfate Foams and Human Cell Cultures.
N. E. Vrana, N. Builles, V. Justin, J. Bednarz, G. Pellegrini, B. Ferrari, O. Damour, D. J. S. Hulmes, and V. Hasirci (2008)
Invest. Ophthalmol. Vis. Sci. 49, 5325-5331
   Abstract »    Full Text »    PDF »
Characterization of Wound Reepithelialization Using a New Human Tissue-Engineered Corneal Wound Healing Model.
P. Carrier, A. Deschambeault, M. Talbot, C. J. Giasson, F. A. Auger, S. L. Guerin, and L. Germain (2008)
Invest. Ophthalmol. Vis. Sci. 49, 1376-1385
   Abstract »    Full Text »    PDF »
ClC-3 is required for LPA-activated Cl- current activity and fibroblast-to-myofibroblast differentiation.
Z. Yin, Y. Tong, H. Zhu, and M. A. Watsky (2008)
Am J Physiol Cell Physiol 294, C535-C542
   Abstract »    Full Text »    PDF »
Regulation of Corneal Fibroblast Morphology and Collagen Reorganization by Extracellular Matrix Mechanical Properties.
D. Karamichos, N. Lakshman, and W. M. Petroll (2007)
Invest. Ophthalmol. Vis. Sci. 48, 5030-5037
   Abstract »    Full Text »    PDF »
Morphologic Characterization of Organized Extracellular Matrix Deposition by Ascorbic Acid Stimulated Human Corneal Fibroblasts.
X. Guo, A. E. K. Hutcheon, S. A. Melotti, J. D. Zieske, V. Trinkaus-Randall, and J. W. Ruberti (2007)
Invest. Ophthalmol. Vis. Sci. 48, 4050-4060
   Abstract »    Full Text »    PDF »
Hypoxia Protects Human Corneal Endothelium from Tertiary Butyl Hydroperoxide and Paraquat-Induced Cell Death In Vitro.
Q. Cheng, T. Nguyen, H. Song, and J. Bonanno (2007)
Experimental Biology and Medicine 232, 445-453
   Abstract »    Full Text »    PDF »
Corneal Activation of Prothrombin to Form Thrombin, Independent of Vascular Injury.
A. Ayala, D. J. Warejcka, M. Olague-Marchan, and S. S. Twining (2007)
Invest. Ophthalmol. Vis. Sci. 48, 134-143
   Abstract »    Full Text »    PDF »
Construction of a complete rabbit cornea substitute using a fibrin-agarose scaffold..
M. Alaminos, M. D. C. Sanchez-Quevedo, J. I. Munoz-Avila, D. Serrano, S. Medialdea, I. Carreras, and A. Campos (2006)
Invest. Ophthalmol. Vis. Sci. 47, 3311-3317
   Abstract »    Full Text »    PDF »
Design of Tissue-engineered Nanoscaffold Through Self-assembly of Peptide Amphiphile.
H. Hosseinkhani, M. Hosseinkhani, and H. Kobayashi (2006)
Journal of Bioactive and Compatible Polymers 21, 277-296
   Abstract »    PDF »
Microkeratome assisted deep lamellar keratoprosthesis.
S Shimmura, H Miyashita, Y Uchino, T Taguchi, H Kobayashi, J Shimazaki, J Tanaka, and K Tsubota (2006)
Br. J. Ophthalmol. 90, 826-829
   Abstract »    Full Text »    PDF »
Multipotent Stem Cells in Human Corneal Stroma.
Y. Du, M. L. Funderburgh, M. M. Mann, N. SundarRaj, and J. L. Funderburgh (2005)
Stem Cells 23, 1266-1275
   Abstract »    Full Text »    PDF »
Enterovirus 70 Binds to Different Glycoconjugates Containing {alpha}2,3-Linked Sialic Acid on Different Cell Lines.
M. R. Nokhbeh, S. Hazra, D. A. Alexander, A. Khan, M. McAllister, E. J. Suuronen, M. Griffith, and K. Dimock (2005)
J. Virol. 79, 7087-7094
   Abstract »    Full Text »    PDF »
Characterization of Growth and Differentiation in a Telomerase-Immortalized Human Corneal Epithelial Cell Line.
D. M. Robertson, L. Li, S. Fisher, V. P. Pearce, J. W. Shay, W. E. Wright, H. D. Cavanagh, and J. V. Jester (2005)
Invest. Ophthalmol. Vis. Sci. 46, 470-478
   Abstract »    Full Text »    PDF »
Differential Expression of Extracellular Matrix Metalloproteinase Inducer (CD147) in Normal and Ulcerated Corneas: Role in Epithelio-Stromal Interactions and Matrix Metalloproteinase Induction.
E. E. Gabison, S. Mourah, E. Steinfels, L. Yan, T. Hoang-Xuan, M. A. Watsky, B. De Wever, F. Calvo, A. Mauviel, and S. Menashi (2005)
Am. J. Pathol. 166, 209-219
   Abstract »    Full Text »    PDF »
Functional Innervation in Tissue Engineered Models for In Vitro Study and Testing Purposes.
E. J. Suuronen, C. R. McLaughlin, P. K. Stys, M. Nakamura, R. Munger, and M. Griffith (2004)
Toxicol. Sci. 82, 525-533
   Abstract »    Full Text »    PDF »
Human corneal equivalent as cell culture model for in vitro drug permeation studies.
S Reichl, J Bednarz, and C C Muller-Goymann (2004)
Br. J. Ophthalmol. 88, 560-565
   Abstract »    Full Text »    PDF »
Sufficiency of the Reactive Site Loop of Maspin for Induction of Cell-Matrix Adhesion and Inhibition of Cell Invasion: CONVERSION OF OVALBUMIN TO A MASPIN-LIKE MOLECULE.
C. Ngamkitidechakul, D. J. Warejcka, J. M. Burke, W. J. O'Brien, and S. S. Twining (2003)
J. Biol. Chem. 278, 31796-31806
   Abstract »    Full Text »    PDF »
Mucin Gene Expression in Immortalized Human Corneal-Limbal and Conjunctival Epithelial Cell Lines.
I. K. Gipson, S. Spurr-Michaud, P. Argueso, A. Tisdale, T. F. Ng, and C. L. Russo (2003)
Invest. Ophthalmol. Vis. Sci. 44, 2496-2506
   Abstract »    Full Text »    PDF »
Myofibroblast Differentiation of Normal Human Keratocytes and hTERT, Extended-Life Human Corneal Fibroblasts.
J. V. Jester, J. Huang, S. Fisher, J. Spiekerman, J. H. Chang, W. E. Wright, and J. W. Shay (2003)
Invest. Ophthalmol. Vis. Sci. 44, 1850-1858
   Abstract »    Full Text »    PDF »
Resazurin Metabolism Assay Is a New Sensitive Alternative Test in Isolated Pig Cornea.
S. Perrot, H. Dutertre-Catella, C. Martin, P. Rat, and J.-M. Warnet (2003)
Toxicol. Sci. 72, 122-129
   Abstract »    Full Text »    PDF »
An Evaluation of Cultivated Corneal Limbal Epithelial Cells, Using Cell-Suspension Culture.
N. Koizumi, L. J. Cooper, N. J. Fullwood, T. Nakamura, K. Inoki, M. Tsuzuki, and S. Kinoshita (2002)
Invest. Ophthalmol. Vis. Sci. 43, 2114-2121
   Abstract »    Full Text »    PDF »
Recovery of Endothelial Function after Vitrification of Cornea at -110{degrees}C.
W. J. Armitage, S. C. Hall, and C. Routledge (2002)
Invest. Ophthalmol. Vis. Sci. 43, 2160-2164
   Abstract »    Full Text »    PDF »
Localization and Characterization of Calcineurin in Bovine Eye.
D. P. Seitz, M. K. Pasha, B. Singh, A. Chu, and R. K. Sharma (2002)
Invest. Ophthalmol. Vis. Sci. 43, 15-21
   Abstract »    Full Text »    PDF »
Interleukin-1{alpha} Released from Epithelial Cells after Adenovirus Type 37 Infection Activates Intercellular Adhesion Molecule 1 Expression on Human Vascular Endothelial Cells.
C.-H. Chang, Y. Huang, A. C. Issekutz, M. Griffith, K.-H. Lin, and R. Anderson (2002)
J. Virol. 76, 427-431
   Abstract »    Full Text »    PDF »
Molecular and Pharmacological Characterization of Muscarinic Receptor Subtypes in a Rat Parotid Gland Cell Line: Comparison with Native Parotid Gland.
C. S. Bockman, M. E. Bradley, H. K. Dang, W. Zeng, M. A. Scofield, and F. J. Dowd (2001)
J. Pharmacol. Exp. Ther. 297, 718-726
   Abstract »    Full Text »
Suppression of interleukin 1{alpha} and interleukin 1{beta} in human limbal epithelial cells cultured on the amniotic membrane stromal matrix.
A. Solomon, M. Rosenblatt, D. Monroy, Z. Ji, S. C Pflugfelder, and S. C G Tseng (2001)
Br. J. Ophthalmol. 85, 444-449
   Abstract »    Full Text »
Chitosan and Gelatin as Engineered Dressing for Wound Repair.
M. G. Tucci, G. Ricotti, M. Mattioli-Belmonte, F. Gabbanelli, G. Lucarini, F. Orlando, C. Viticchi, A. Bigi, S. Panzavolta, N. Roveri, et al. (2001)
Journal of Bioactive and Compatible Polymers 16, 145-157
   Abstract »    PDF »
Corneal Organ Culture Model for Assessing Epithelial Responses to Surfactants.
K.-P. Xu, X.-F. Li, and F.-S. X. Yu (2000)
Toxicol. Sci. 58, 306-314
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)