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Corneal equivalent shows promise as replacement for eye bank tissue
Comparable changes in transparency and gene expression were found during research.
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OTTAWA — After 5 years of research, an equivalent to the human cornea has been constructed. The functional human corneal equivalent was constructed from cell lines and comprises the three main layers of the cornea (epithelium, stroma and endothelium). The fabricated cornea also mimics human corneas in key physical and physiological functions, including morphology, biochemical marker expression, transparency, ion and fluid transport, and gene expression.
“What we have described in the paper is a prototype, to show that we can reconstruct a cornea in vitro,” said lead author May Griffith, PhD, an assistant professor of ophthalmology at the University of Ottawa Eye Institute. “We’re now tackling the tough part, which is making the engineered cornea ready for human transplantation.” Study results appeared in the Dec. 10, 1999, edition of Science (Volume 286).
Dr. Griffith and her colleagues completed the prototype last summer. Since then, a second prototype has been engineered, which also has been submitted for publication. “However, we’re more excited about the first prototype because it’s always more challenging to imitate Mother Nature. We used natural materials and a cell-based system,” she said. In contrast, the second prototype entailed modifying separate surfaces of synthetic polymers.
Comparable changes
The researchers evaluated changes in transparency and gene expression. “For gene expression, we used 5% sodium dodecyl sulfate, which is a surfactant that causes mild to moderate injury to the cornea,” Dr. Griffith said. Among the genes studied that are normally upregulated during corneal wound healing were interleukin-1 alpha and 6, basic fibroblast growth factor and collagen I. “Fabricated corneas showed greater sensitivity in comparison with human eye bank tissues that were available for research,” Dr. Griffith said.
Five chemical formulations also were used to assess changes in light transmission after exposure to chemicals. “From a practical standpoint, using sophisticated molecular approaches such as polymer chain reaction to examine changes in gene expression is not realistic for industrial testing. Transparency testing, on the other hand, is simple, inexpensive and is used in both rabbit eye tests and human clinical practice,” Dr. Griffith said. Study results indicated that changes in transparency in the corneal equivalents mirrored those of excised rabbit and human eye bank corneas.
Functional human corneal equivalents could eventually become a substitute for animal testing. “Right now we are in the process of standardizing protocols at different laboratories in North America and Europe,” Dr. Griffith said. There also could be drug efficacy testing, such as with wound healing. In any event, Dr. Griffith believes engineered corneal equivalents would be less expensive than relying on animal corneas. “I can’t speak for the United States, but it costs me $60 a rabbit [in Canada], plus housing and veterinarian fees, whereas I can build myself a cornea for a lot less,” she said.
Transplantation
Before transplantation can become a reality, though, “the corneal construct will need to be strengthened considerably,” Dr. Griffith said. In addition, “methods for harvesting and incorporating either stem cells or autologous corneal cells into the implant need to be developed.” There also are the variables of funding, availability of good research personnel and regulatory hurdles.
W. Bruce Jackson, MD, is director general at the University of Ottawa Eye Institute. “Our initial premise for developing an artificial cornea was our feeling that more research was needed in wound healing following refractive surgery,” he said. “At that time, we were primarily doing photorefractive keratectomy [PRK]. We were looking to develop a model that we could actually perform PRK on, and then keep that model going 3 or 4 weeks while watching the wound healing response. Obviously as we continued research, the model took on a life of its own.”
Dr. Jackson said he and his associates are not studying the effects of laser in situ keratomileusis (LASIK) on the fabricated cornea because “the stroma is really too flimsy. There isn’t enough structural rigidity.” Future plans, therefore, involve “basically developing a curvature to the cornea and a stromal structure that may allow us to evaluate wound healing from LASIK,” he said.
Because of the increasing number of people undergoing refractive laser surgery today, and the demographics of an aging population, “we are facing a potential shortage of ideal cornea donors, coupled with an increased demand for transplantable corneas,” Dr. Jackson said.
Dr. Jackson is hopeful that human implantation clinical trials will be well under way in 5 years. “Another exciting opportunity is the possibility of taking a person’s own corneal cells and growing those into an artificial cornea,” he said. Such a scenario would drastically reduce the risk of rejection.
Dr. Griffith added that there are other research teams pursing artificial corneas. “We don’t know which one or ones will be used eventually,” she said. Nonetheless, “the whole possibility of making replacement tissue in general is very exciting to us.”
For Your Information:
- May Griffith, PhD, can be reached at University of Ottawa Eye Institute, Ottawa Hospital–General Campus, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada; +(1) 613-737-8822; fax: +(1) 613-737-8836; e-mail: mgriffith@ogh.on.ca. Dr. Griffith has no direct financial interest in any of the products mentioned in this article, nor is she a paid consultant for any companies mentioned.
- W. Bruce Jackson, MD, can be reached at University of Ottawa Eye Institute, Ottawa Hospital–General Campus, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada; +(1) 613-737-8759; fax: +(1) 613-737-8374; e-mail: bjackson@ogh.on.ca. Dr. Jackson has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.