Evaluation Of Optic Nerve Morphology And Aqueous Humor Dynamics In A Vascularized Whole Eye Transplantation Model
Liwei Dong, M.D.1, Yang Li, M.D.1, Chiaki Komatsu, M.D.1, Maxine R. Maxine, M.D.1, Hongkun Wang, M.D.1, Bo Wang, B.S.2, Yolandi van der Merwe, B.Eng.3, Edward H. Davidson, M.A. ,M.B.B.S.1, Mario G. Solari, M.D.1, Shuzhong Guo, M.D., Ph.D.4, Jeffrey L. Goldberg, M.D., Ph.D.5, Larry Benowitz, M.D., Ph.D.6, Gadi Wollstein, M.D.2, Joel S. Schuman, M.D.2, Vijay S. Gorantla, M.D., Ph.D.1, Kevin C. Chan, Ph.D.2, Kia M. Washington, M.D.1.
1Department of Plastic Surgery, UPMC, Pittsburgh, PA, USA, 2UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 3Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA, 4Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China, 5Department of Ophthalmology, Shiley Eye Center, University of California San Diego, La Jolla, CA, USA, 6Department of Neurosurgery, Harvard University, Boston, MA, USA.
Purpose: Vision loss due to degenerative diseases and ocular trauma affects millions of people worldwide. Whole eye transplantation (WET) would provide a solution for those with irreversible vision loss. The purpose of this study is to evaluate the viability, structural integrity and function of our orthotopic whole eye transplant model by assessing aqueous humor dynamics using gadolinium (Gd)-enhanced MRI, optic nerve structural integrity with diffusion tensor MRI (DTI) and retinal ganglion cell (RGC) viability with Manganese (Mn)-enhanced MRI.
Methods: Syngeneic transplants were performed in 5 Lewis (RT1l) rats. Four animals were scanned at 3 weeks and 1 animal was scanned at 10 weeks after transplantation. After Gd- enhanced MRI imaging, the initial rate of Gd increase, peak % Gd signal enhancement, time-to-peak, fractional anisotropy (FA), axial diffusivity (λ//) and radial diffusivity (λ┴) were calculated. DTI parametric maps were computed using DTIStudio. Manganese (Mn)-enhanced MRI was used after WET.
Results: Limited Gd-enhancement was observed in the vitreous with no significant difference between eyes (two-tailed paired t-tests, p>0.05). T2-weighted images revealed comparable optic nerve morphology, whereas in the prechiasmatic optic nerves, DTI quantitation showed significantly lower FA and λ// by 54±6.1% and 24.9±5.7%, respectively, and a significant increase in λ┴ by 83±29.5% in comparison (two-tailed paired t-tests, p<0.05). Mn-enhanced MRI data suggest RGC viability.
Conclusion: Aqueous humor dynamics and blood-ocular barriers are preserved and preliminary data suggest that RGCs may be viable after transplantation. Future studies will examine approaches for regaining neuronal structure and function of our whole eye transplant model.
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