Whole Eye Transplantation in the Rodent: Long-Term Survival and Effects on the Unoperated Partner Eye
Wendy Chen, MD, MS1, Lin He, MD1, Yang Li, MD2, Chiaki Komatsu, MD1, Maxine R. Miller, MD1,3, Yolandi van der Merwe, B. Eng.4,5, Katie Lucy, BS6, Huamin Tang, MD8, Ian Rosner, BS1, Mario G. Solari, MD1, Gadi Wollstein, MD6, Joel S. Schuman, MD6, Kevin C. Chan, PhD6, Kia M. Washington, MD1,7.
1University of Pittsburgh Medical Center Department of Plastic Surgery, Pittsburgh, PA, 2Fourth Military Medical University Department of Plastic and Reconstructive Surgery, Xi'an, China, 3University of Pittsburgh Medical Center Department of Ophthalmology, PIttsburgh, PA, 4University of Pittsburgh Medical Center Department of Ophthalmology, Department of Bioengineering, Pittsburgh, PA, 5University of Pittsburgh Neuroimaging Laboratory, Pittsburgh, PA, 6New York University Langone Eye Center, New York City, NY, 7Veterans Administration Pittsburgh Healthcare System University of PIttsburgh, Pittsburgh, PA, 8Second Affiliated Hospital of Guang Xi Medical University, Guang Xi, China
PURPOSE: Globally, 39 million people suffer from blindness. Whole eye transplantation (WET) offers the opportunity to provide a viable optical system to recipients with irreversible vision loss. We have previously established a viable orthotropic model for vascularized whole eye transplant in the rat. The purpose of our study is to evaluate gross morphology, structural integrity and aqueous humor dynamics in a long-term WET survivor, as well to evaluate for any adverse effects of WET in the unoperated, contralateral eye.
METHODS: Syngeneic whole eye transplants were performed with Lewis rats. The donor flaps included ocular tissues anterior to the optic chiasm, eyelid and periorbital tissue, and external ear. The recipient site was prepared by removing a similar region of skin and ocular tissue, with optic nerve division at its exit from the globe, vascular anastomoses, and optic nerve coaptation. Optical coherence tomography (OCT), gadolinium-enhanced magnetic resonance imaging (Gd-enhanced MRI) and electroretinography (ERG) were performed to evaluate the viability and structural integrity of the eyes of the long-term WET survivor and compared with a naive, age-matched control.
In a subsequent series of syngeneic transplants, we evaluated the unoperated, contralateral eye with OCT, slit lamp exam, fundoscopy, and histology.
RESULTS: The long-term WET survivor and corresponding control animal were >400 days old at time of evaluation. Corneal opacification prohibited OCT imaging of the retina of the transplanted eye. OCT of the cornea and retina of the contralateral eye corresponded with the naive eyes of the control rat. Gd-enhanced MRI imaging revealed existing aqueous humor dynamics in the contralateral unoperated eye in the transplanted eye had a normal electrical response with ERG, which was similar to the control. In the transplanted eye, aqueous humor dynamics was compromised, and there was no evidence of electrical response with ERG analysis.
As for our follow-up series of syngeneic transplants (n=6, sacrifice at 3mos), we continued to find no abnormalities in the contralateral eye with respect to OCT, slit lamp exam, fundoscopy, and histology.
CONCLUSION: In this study, we demonstrate findings in a long-term survivor. We did not identify any adverse changes in structural integrity and function in the contralateral eye >400 days after WET in comparison to the age-matched control eyes. This preservation of the structure and function of the contralateral eye was recapitulated in a subsequent series of animals.
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