Allogeneic Whole Eye Transplantation in Macaques Achieves 19-Day Graft Survival With Structural and Functional Viability.

Abstract

PURPOSE: Whole eye transplantation (WET) is a promising approach for vision restoration in severe ocular damage. This study pioneers an allogeneic whole-eye transplantation model in non-human primates, designed to: (1) Establish standardized surgical protocols; (2) Overcome critical barriers to clinical translation-specifically immune rejection, functional visual restoration, and sustained graft viability; (3) Provide preclinical foundations for advancing human eye transplantation into clinical practice. DESIGN: Experimental animal study METHODS: Four cynomolgus macaques underwent unilateral whole-eye transplantation with distinct vascular anastomosis sequences using microsurgery, surgical navigation, and hypothermic perfusion: Strategy 1 (n = 2) implemented ``Artery then vein'' anastomosis, while Strategy 2 (n = 2) employed "Vein then artery" anastomosis. Recipients received perioperative standard triple immunosuppression (tacrolimus + mycophenolate mofetil + methylprednisolone). Transplanted eye structure and function were monitored via multimodal ophthalmic imaging and full-field electroretinography. Postoperative rejection was determined by ocular and dermal manifestations. RESULTS: The "Vein then artery" procedure achieved 19-day graft survival with intact circulation, normal intraocular pressure, and clear ocular media. Functional preservation was evidenced by detectable ERG signals and confirmed retinal perfusion. Rejection signs emerged on day 17, prompting termination on day 19. Histological analysis revealed reduced retinal ganglion cell density and inflammatory cell infiltration. The ``Artery then vein'' strategy caused acute intraocular pressure (IOP) elevation (49 mmHg), corneal edema, retinal disruption, and graft failure within 3 days. CONCLUSIONS: This research establishes the first proof-of-concept for allogeneic whole-eye transplantation in non-human primates, achieving 19-day graft survival with preserved structural integrity and partial retinal function. Overcoming postoperative immune rejection and functional reconstitution of retina-cortical connectivity remain pivotal challenges in WET. Given the profound anatomical homology of ocular structures between cynomolgus macaques and human, this model provides a translational foundation for addressing core barriers to clinical Whole eyeball transplantation.