Eyeworld

EW CORNEA 90 September 2015 by Matt Young and Gloria D. Gamat EyeWorld Contributing Writers Is xenotransplantation the future of corneal transplantation? P ig corneas could be the answer for millions of people worldwide with corneal blindness. The worldwide shortage of cor- neas from deceased human donors is a pressing issue. Also, the increas- ing incidence of infectious diseases in potential donors, particularly human immunodeficiency virus (HIV), and the increasing popularity of refractive surgery in developed countries continue to reduce the supply of available human corneas. Currently, the global require- ment for corneal transplantation is beyond the availability of deceased human donor corneas. Surgeons from the Thomas E. Starzl Transplantation Institute, University of Pittsburgh, believe that xenotransplantation is the future of corneal transplantation. "The pig cornea is structural- ly similar to the human cornea," explained David K. Cooper, MD, professor of surgery, Thomas E. Starzl Transplantation Institute. While there are sufficient cor- neas from deceased human donors in most western countries, that is not the case in many parts of the world, particularly Asia and Africa. "[Xenotransplantation] would enable thousands of blind patients to undergo corneal transplantation and therefore be able to see again," said Hidetaka Hara, MD, research assistant and professor of surgery, Thomas E. Starzl Transplantation Institute. "The biomechanical proper- ties of human and pig corneas are similar," Drs. Cooper and Hara reported in their first paper on this subject, published in Cornea in April 2011. The subject has emerged as a hot topic with a growing body of evidence. "Studies in animal models of corneal xenotransplantation have documented both humoral and cellular immune responses that play roles in xenograft rejection. Recent progress in the genetic manipulation of pigs has led to the prospect that the remaining immunological barri- ers will be overcome. There is every reason for optimism that corneal xenotransplantation will become a clinical reality within the next few years." Suitability of xenotransplantation for corneal transplants Numerous studies have reported successful xenotransplants, which involved corneas from pigs, sheep, dogs, and rabbits. However, most of the xenografts were rejected within 1 month, especially in those from widely disparate species. In terms of anatomy and physi- ology, there are many similarities be- tween pig and human corneas; this was reported in Survey of Ophthalmol- ogy as early as 2000. These findings were then corroborated by a paper published in the Journal of the Korean Ophthalmological Society (2006) and later on in the Scandinavian Journal of Laboratory Animal Science (2008). Ethically and commercially, according to Dr. Cooper and col- leagues (Annual Review of Medicine, 2002), pigs represent an acceptable choice as an alternative source of organs for humans. Dr. Cooper and colleagues reported in the journal Transplan- tation in July 2007 that in terms of immunology, the pig is less desirable compared to a non-human primate as a source of organs or tissue for human transplantation because of the genetic distance between pigs and humans. However, as report- ed by Pierson and colleagues in Xenotransplantation in September/ October 2009, advances in genetic engineering are steadily enabling pig tissues to be resistant to injury from the human immune response. In addition, Dr. Cooper noted, because the cornea is an immune-privileged tissue and is not immediately vas- cularized, it is likely to be a better xenograft compared to other organ xenografts. Furthermore, according to Drs. Cooper and Hara, selected genetic modifications to the source pig may render the cornea comparable, or even superior, to a human cornea in terms of its ability to resist rejection, even in the absence of local steroid therapy. "Pig corneas [and other tissues and organs] are rejected by humans and other primates [e.g., monkeys], but pigs can be genetically engi- neered to protect their tissues from the human immune response," Dr. Cooper explained. In addition, Dr. Cooper said there are numerous immunosup- pressive drugs that will suppress or prevent rejection. Explaining how pig corneas could fill the need for corneal transplantation, he said, "The use of corneas from genetically engineered pigs and treatment of the patient with new immunosuppres- sive drugs should prevent rejection and allow long-term survival of pig corneal grafts in humans." For the purpose of xenotrans- plantation, pigs would be housed The potential of pig corneas for corneal transplantation T he United States is one of very few countries around the world where donor corneal tissue supply can match the demand. Internationally, there is a significant shortage of human corneal donors. While options such as biosynthetic corneas have achieved some success in small patient series, many scientific groups around the world continue to seek out alternatives. Xenotransplantation is a term used to describe when donor tissue from another species is used for humans. While it may still sound like science fiction, using pigs as a source animal for corneal tissue is being heavily researched. This month's "Cornea editor's corner of the world" focuses on the fascinating potential of pig corneas to be used for corneal transplantation. David Cooper, MD, and Hidetaka Hara, MD, discuss the basis for using pig corneas, the role of genetic engineering, and rejection issues in corneal xenotransplantation. Clara C. Chan, MD, FRCSC, FACS, cornea editor Cornea editor's corner of the world " The use of corneas from genetically engineered pigs and treatment of the patient with new immunosuppressive drugs should prevent rejection and allow long-term survival of pig corneal grafts in humans. " –David K. Cooper, MD

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