Wendy Chen, MD, MS
,
Plastic Surgery, University of Pittsburgh, Pittsburgh, PA
Jila Noori, MD
,
Bascom Palmer Eye Institute, University of Miami, Miami, FL
Lin He, MD
,
Department of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliate Hospital of Xi’an Jiaotong University, Xi'an, China
Chiaki Komatsu, MD
,
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA
Maxine R. Miller, MD
,
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA
Ian Rosner, BS
,
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA
Wensheng Zhang, MD, PhD
,
Plastic Surgery, University of Pittsburgh, Pittsburgh, PA
Kira L Lathrop, MAMS
,
Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA
Joshua M Barnett, BS
,
University of Pittsburgh School of Medicine, Pittsburgh, PA
Yong Wong, MD
,
Department of Plastic Surgery, University of Pittsbugh Medical Center, Pittsburgh, PA
Bing Li, MD
,
Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
Mario G. Solari, MD
,
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA
Charleen T Chu, MD, PhD
,
McGowan Institute for Regenerative Medicine, Pittsburgh, PA
Kia M Washington, MD
,
Department of Plastic Surgery, VA Pittsburgh Healthcare System, Pittsburgh, PA
PURPOSE: Visual impairment and blindness present significant economic, social and personal burdens for millions of patients and caregivers around the world. Whole eye transplantation (WET) is a potential solution. Our lab has established a viable rodent model with promising results in syngeneic transplants. To investigate allotransplantation, successful immunosuppression is necessary. Tacrolimus monotherapy is successful in rodent VCA and has possible neuroprotective effects in the central nervous system and injured optic nerve, but its efficacy in WET is unknown. Here, we present survival of allograft WET treated with Tacrolimus monotherapy.
METHOD: Brown-Norway to Lewis rat transplants were performed (n=6), followed by daily intraperitoneal 1mg/kg Tacrolimus injection. Animals were examined at weeks 1, 3, 5, and 6, and compared to syngeneic transplants. Structure and blood flow of the eye and retina were studied using Optical Coherence Tomography (OCT). A retina specialist ophthalmologist performed anterior segment examination, fundoscopy, indirect ophthalmoscopy, and tonometry for intraocular pressures. Animals were sacrificed at 6 weeks. Specimens of the transplanted globe, external ear, eyelid, bone and vessel anastomoses were stained with H&E and interpreted by an ocular pathologist.
RESULT: Compared to syngeneic transplants, allografts demonstrated comparable corneal thickening, retinal thinning, and blood flow in the central retinal artery and vein (OCT). Intraocular pressures were normal and comparable to syngeneic transplants. On clinical examination, both groups had mild corneal anomalies, but allografts had more frequent fundus and optic nerve ischemia (moderate). Histologically, both groups had global ocular chronic inflammation, some degree of retinal degeneration, but, in contrast to allografts, syngeneic transplants actually showed consistent degeneration of the optic nerve.
CONCLUSION: This is the first study of orthotopic allograft eye transplantation and immunosuppression. Compared to syngeneic transplants, allografts had increased ischemia, but less optic nerve degeneration, without signs of rejection. Overall preservation of ocular structures is an exciting first step. With this, we can begin to explore innumerable new questions in eye transplantation.