A Preclinical Swine Model for Whole Eyeball Transplantation - Planning and Procedural Aspects
Vasil E. Erbas, MD1, Huseyin Sahin, MD1, Sinan Oksuz, MD2, Liwei Dong, MD1, Maxine R. Miller, MD1, Golnar Shojaati, MD1, Gadi Wollstein, MD1, Kevin C. Chan, PhD1, Ian Sigal, PhD1, Nataliya Kostereva, PhD1, Shailesh Raval, PhD1, Tamer Ibrahim, PhD1, Jeffrey L. Goldberg, MD3, Larry Benowitz, MD4, Joel S. Schuman, MD1, Fatih Zor, MD5, Mario Solari, MD1, Kia M. Washington, MD1, Vijay S. Gorantla, MD, PhD1.
1University of Pittsburgh, Pittsburgh, PA, USA, 2Gulhane Askeri Tip Akademisi, Ankara, Turkey, 3Stanford University School of Medicine, Palo Alto, CA, USA, 4Harvard Medical School, Boston, MA, USA, 5Gulhane Askeri Tip Akademisi, Istanbul, Turkey.
Purpose: Whole eyeball transplantation (WET) is the holy grail of vision restoration and is conceptually the most challenging of vascularized composite allografts (VCA). The swine eye is analogous to the human eye and is the ideal model for human WET. Our goal was to develop the protocols (surgical planning/procedures/post operative imaging /evaluations) as a foundation for a robust, large animal, preclinical WET model.
Methods: WET techniques were optimized in 17 fresh tissue swine dissections. An eyeball-periorbital VCA subunit with extra ocular muscles, and optic nerve (ON) was raised superolaterally and anastomosed to the recipient external ophthalmic artery (EOA) after exenteration. Methylene blue perfusion and microfil vascular mapping of central retinal artery (CRA)/vortex veins/ciliary plexus was done. Orbital contents and ON were imaged with DCE-DTI-MRI [T1/T2 MRI at 3T/7T/9.4 Tesla]. Advanced protocols for histopathology, immunohistochemistry, epoxy-embedding, corrosion casting, optical coherence tomography (OCT)/tonometry/fundoscopy/ERG were optimized and surgical techniques for ON crush, cut and coaptation established.
Results: Like humans, the swine retina is holangiotic and the ON has a lamina cribrosa. However, the CRA is absent with a large EOA. OCT/MRI allowed real-time, high definition, non-invasive, in situ, micron-scale, cross-sectional visualization of structure/topography of ocular structures.
Conclusion: Our study is the critical first step towards a swine WET model optimized for viability, retinal survival, ON regeneration and reintegration while documenting key immune responses, and enabling key neuro-immuno-therapeutic interventions.
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