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The aim of this study was to establish a novel Whole Eye Vascularized Composite Allotransplantation (VCA) model that includes the eyeball, adnexa and soft tissues with optic nerve (ON), to evaluate the immunological, neuroregeneration and graft survival outcomes.Sprague-Dawley rats received heterotopic vascularized Whole Eye Transplants (WET). Each periorbital flap included the globe, and surrounding tissues based on common carotid artery and external jugular vein as vascular pedicle (Figure 1 and 2). Viability was confirmed by angiography, MRI and clinical examination. Histopathology of protocol skin biopsies were scored for Banff grading. The globe, adnexal and ON tissues were analyzed for acute rejection and/or nerve regeneration at endpoint of 30 days or Grade 3 rejection (whichever was earlier).Macroscopic evaluation confirmed flap viability (Figure 3). The MR evaluation revealed loss of globe volume by 35% after transplantation. Histological exam of globe and adnexal tissues showed unique and differential patterns of rejection, predominantly involving macrophage and neutrophil infiltration. Optic nerve sectioning revealed a degeneration pattern with no evidence of regeneration.This is the first study of successful heterotopic WET in the literature. This model offers promise and potential in immunological, neuroregeneration, drug delivery, cellular therapies, imaging and tissue engineering studies involving optic nerve, retina or eyeball tissues.