Demonstration of technical feasibility and viability of whole eye transplantation in a rodent model

Abstract

Whole eye transplantation (WET) holds promise for vision restoration in devastating/disabling visual loss (congenital or traumatic) not amenable to surgical or neuroprosthetic treatment options. The eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. Anatomically and immunologically, the eye is unique due to its avascular (cornea) and highly vascular (retina) components. Our goal was to establish technical feasibility, demonstrate graft viability, and evaluate histologic changes in ocular tissues/adnexae in a novel experimental model of WET that included globe, adnexal, optic nerve (ON), and periorbital soft tissues. Outbred Sprague-Dawley rats (n = 5) received heterotopic vascularized WET from donors. Each WET included the entire globe, adnexa, ON, and periorbital soft tissues supplied by the common carotid artery and external jugular vein. Viability and perfusion were confirmed by clinical examination, angiography and magnetic resonance imaging (MRI). Globe, adnexal, and periorbital tissues were analyzed for histopathologic changes, and the ON was examined for neuro-regeneration at study endpoint (30 days) or Banff Grade 3 rejection in the periorbital skin (whichever was earlier). Gross examination confirmed transplant viability and corneal transparency. Average operative duration was 64.0 ± 5.8min. Average ischemia time was 26.0 ± 4.2min. MRI revealed loss of globe volume by 36.0 ± 2.8% after transplantation. Histopathology of globe and adnexal tissues showed unique and differential patterns of inflammatory cell infiltration. The ON revealed a neurodegeneration pattern. The present study is the first in the literature to establish an experimental model of WET. This model holds significant potential in investigating mechanistic pathways, monitoring strategies or developing management approaches involving ocular viability, immune rejection, and ON regeneration after WET.