New Technique May Improve Corneal Transplant Survival

Researchers have developed a potential new strategy for improving outcomes in corneal transplant surgeries by injecting vasoactive intestinal peptide into the eye

Boston, Mass. — A new study led by Massachusetts Eye and Ear researchers reports for the first time that injection of the neuropeptide vasoactive intestinal peptide (VIP) directly into the eyes of mice enhanced corneal graft survival. Published online in the American Journal of Pathology, the study shows that VIP produced other benefits, including acceleration of endothelial wound closure, protection of corneal endothelial cells (CEnCs), and improved corneal graft clarity. If proven successful in clinical studies, this novel approach may help alleviate vision loss in many patients with corneal disease.

“The successful outcome of corneal transplantation mainly relies on the density and function of CEnCs, which keep the graft transparent,” said study author Ahmad Kheirkhah, MD, currently an Assistant Professor of Ophthalmology at University of Texas San Antonio, who completed the research when he was at Mass. Eye and Ear. “To improve the outcomes of corneal transplantation, various strategies have been employed to prevent immune-mediated graft rejection or enhance survival and function of CEnCs. However, an effective method has remained elusive so far.”

In this study, researchers evaluated the effects of VIP on corneal tissue in cell culture and living animals who received corneal transplants. VIP, a 28 amino acid neuropeptide, is recognized as an immunoregulatory and protective factor in various organ systems. VIP is found in the aqueous humor of the eye and may be secreted by CEnCs. Although it is known that VIP can help preserve the integrity of CEnCs and may be used by eye banks to improve the survival of donor corneas, it has been unclear until now whether administration of VIP in vivo after corneal transplantation could improve graft survival.

The researchers observed numerous ways in which VIP may exert beneficial effects. In cell cultures of human corneal endothelial cells, VIP accelerated wound healing compared to controls. When corneal endothelial cells were exposed to the substances known to induce apoptosis (cell death), such as interferon-γ or tumor necrosis factor-α, VIP showed a dose-dependent protective effect.

In live mice that underwent corneal transplantation, grafts were more transparent in VIP-treated mice compared to controls four to eight weeks after transplantation. Eight weeks after transplantation, 85 percent of VIP-treated grafts survived compared to 0 percent of control grafts, and corneal endothelial cell density was higher in VIP-treated corneas compared to controls.

“Millions of patients around the world are blind due to corneal opacity, and they are in dire need of corneal transplantation,” said senior author Reza Dana, MD, MPH, MSc, Director of the Cornea and Refractive Surgery Service at Mass. Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School. “Unfortunately, there is a significant shortage of donor corneas across the world. On the other hand, many donated corneas cannot be used for transplantation due to inadequate endothelial cells. Moreover, corneal transplants can deteriorate over time due to continuous loss of CEnCs. If confirmed in further clinical studies, we believe that the use of VIP will increase the number of donated corneas suitable for transplantation and improve the outcomes of corneal transplantation.”

Corneal transplantation is the most common form of tissue transplantation in medicine today. These procedures are performed to correct the visual loss that occurs when the cornea, the transparent structure forming the front of the eye, becomes opaque (cloudy). Corneal opacity can result from many eye diseases.

In addition to Ahmad Kheirkhah and Reza Dana, authors on the American Journal of Pathology report include Vannarut Satitpitakul of the Schepens Eye Research Institute of Massachusetts Eye and Ear/Harvard Medical School and Chulalongkorn University in Bangkok, Thailand, Zhongmou Sun, Kunal Suri, Afsaneh Amouzegar, Kishore Katikireddy and Ula Jurkunas of the Schepens Eye Research Institute of Massachusetts Eye and Ear/Harvard Medical School.

This study was funded in part by the Eye Bank Association of America, Eversight Eye Bank, the New England Cornea Transplant Fund, the Harvard Cornea Center of Excellence Fellowship, and the Massachusetts Lions Club.

About Massachusetts Eye and Ear

Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. Specializing in ophthalmology (eye care) and otolaryngology-head and neck surgery (ear, nose and throat care), Mass. Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world's largest community of hearing and vision researchers, Mass. Eye and Ear has pioneered new treatments for blindness, deafness and diseases of the head and neck. Our scientists are driven by a mission to discover the basic biology underlying these conditions and to develop new treatments and cures. In the 2018-2019 "Best Hospitals Survey," U.S. News & World Report ranked Mass. Eye and Ear #4 in the nation for eye care and #6 for ear, nose and throat care. For more information about life-changing care and research at Mass. Eye and Ear, please visit our blog, Focus, and follow us on Twitter and Facebook.

About Harvard Medical School Department of Ophthalmology

The Harvard Medical School Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 400 full-time faculty and trainees work at nine Harvard Ophthalmology affiliate institutions, including Massachusetts Eye and Ear, Schepens Eye Research Institute of Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.