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Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation
Yang Li, MD., PhD.1, Chiaki Komatsu, MD.1, Bo Wang, BS.1, Maxine R. Miller, MD.1, Hongkun Wang, MD.1, Yolandi van der Merwe, B.Eng.1, Leon C. Ho, B.Eng.1, Nataliya Kostereva, PhD.1, Wensheng Zhang, MD., PhD.1, Bo Xiao, MD., PhD.1, Edward H. Davidson, MA., MBBS.1, Mario G. Solari, MD.1, Michael B. Steketee, PhD.1, Shuzhong Guo, MD., PhD.2, Lawrence Kagemann, MD.1, Gadi Wollstein, MD.1, Joel S. Schuman, MD.1, Kevin C. Chan, PhD.1, Vijay S. Gorantla, MD., PhD.1, Kia M. Washington, MD.1.
1University of Pittsburgh, Pittsburgh, PA, USA, 2Fourth Military Medical University, Xi'an, China.
Approximately 37 million people throughout the world suffer from blindness. The permanent nature of blindness from macular degeneration, diabetic retinopathy, glaucoma, and trauma results in a significant decline in quality of life, ability to return to the workforce, and presents pressing challenges to the medical and military communities. The permanent nature of vision loss is largely due to the inability of retinal ganglion cells to regenerate. Whole eye transplantation (WET) gives the opportunity to provide viable retinal ganglion cells and the entire optical system to recipients with vision loss and irreversible injury to the eye. We have recently established a whole eye transplant model in the rat. The purpose of our study is to evaluate viability, structural integrity, and functional outcome after whole eye transplantation.
All syngeneic transplants were performed in Lewis (RT1l) rats. The donor flap, pedicled by the common carotid artery and external jugular vein, is composed of all ocular tissue distal to the optic chiasm, a portion of the temporal bone, and the skin tissues of the eyelids and external ear. The recipient site was prepared by removing a similar region of skin tissue and the eye socket content, with the optic nerve cut at the base of the globe. A nerve apposition between the donor and recipient optic nerve was performed. Slit lamp examination and OCT imaging of the cornea, lens and retina were performed weekly after transplantation to evaluate viability and structural integrity. Gadolinium enhanced MRI was employed to evaluate aqueous humor dynamics and blood-ocular and aqueous-vitreous barrier integrity of the transplanted eye after systemic administration of gadolinium contrast agent mimicking soluble aqueous humor components.
15 out of 22 rats survived the surgical procedure while maintaining visual transparency of the anterior eye via slit lamp examination. All eyes experienced certain degrees of corneal neovascularization. OCT imaging confirmed transparency of the cornea and lens, preservation of the structural layers of the retina, and blood flow throughout the eye. Gadolinium-enhanced MRI showed the presence of aqueous humor dynamics and preserved integrity of the blood-ocular and aqueous-vitreous barriers in the transplanted eye. Histology confirmed neovascularization of the cornea as well as preservation of the structural integrity of the retina, with the exception of thinning of the retinal ganglion cell layer.
We have established a viable orthotopic model for vascularized whole eye transplantation in the rat. Maintenance of structural integrity and viability were confirmed by slit lamp examination, OCT, MRI and histology. The model is ideal for examining viability, functional return and immunology in whole eye transplantation.
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