Background
To pioneer vascularized composite allotransplantation (VCA) of the human eye as a clinical reality, our group has developed the first orthotopic model for eye transplantation in the rat for testing of immunomodulation and neuroregeneration therapies. We have also performed human cadaveric studies to design surgical protocols for donor and recipient procedures ahead of advancing to a non-human primate surgical model of eye transplantation Non-invasive methodologies of graft monitoring are paramount to development of this model as well as for clinical practice in future transplantation programs.
Methods
Young adult male rhesus macaques (3–4 years) were subjected to positron emission tomography (PET) and computed tomography (CT) imaging. Structural CT assessments were performed to provide critical biometric morphology assessments of the orbit. Contrast-enhanced CT angiography (CTA) was used to map the vasculature of the orbital region to define arterial and venous territories. In each imaging session, assessment was made using [15O]H2O PET (for soft tissue perfusion), [18F]2-fluoro-2-deoxyglucose (FDG) PET (for tissue viability indexed by tissue metabolic rate of deoxyglucose), [18F] sodium fluoride PET for osteogenic viability and selective dopamine D4 radiotracer [11C]CPMB PET for retina viability. Relative intensities of tracer generated by PET studies were analyzed with qualitative imaging as well as through quantitative PET techniques.
Results
CT biometric data confirmed high fidelity morphological compatibility between globes and bony orbits of subjects. CTA confirmed perfusion that permits feasibility of donor and recipient surgical procedures for eye transplantation in a non-human primate model based on a single arterial (ophthalmic artery) and single venous (superior ophthalmic vein) pedicle CTA generated arterial and venous territory maps of orbit and periorbita with pedicle lengths and calibers relevant to surgical planning for eye transplantation were created. [15O]H2O, [18F] FDG, [18F] sodium fluoride and [11C]CPMB PET can quantatively measure soft tissue perfusion, soft tissue viability, osseous viability and retinal viability respectively.
Conclusions
These protocols serve as a benchmark for further development of nonhuman primate model for vascularized composite allotransplantation of the eye, and for ultimately potentiating a clinical program of vision restoration transplantation surgery.