In Vivo Evaluation Of The Retina And Optic Nerve After Whole Eye Transplantation Using Optical Coherence Tomography, Manganese-enhanced Magnetic Resonance Imaging And Electroretinography
Chiaki Komatsu, M.D.1, Lin He, M.D.1, Yolandi van der Merwe, B.Eng.2, Maxine R. Miller, M.D.1,3, Katie A. Lucy, B.S.4, Huamin Tang, M.D.1, Ian Rosner, B.S.1, Yang Li, M.D.,Ph.D.1, Michael Steketee, Ph.D.3, Gadi Wollstein, M.D.4, Mario G. Solari, M.D.1, Joel S. Schuman, M.D.4, Kevin C. Chan, Ph.D.3,5, Kia M. Washington, M.D.1,6.
1Department of Plastic Surgery,University of Pittsburgh, Pittsburgh, PA, USA, 2Department of Bioengineering,University of Pittsburgh, Pittsburgh, PA, USA, 3Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA, 4Department of Ophthalmology, New York University School of Medicine, New York, NY, USA, 5Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA, USA, 6Veterans Administration Pittsburgh Healthcare System, Pittsburgh, PA, USA.
Purpose: The purpose of this study is to evaluate the viability and structural integrity of the visual system with in vivo optical coherence tomography (OCT) , manganese-enhanced magnetic resonance imaging (MEMRI) and electroretinography(ERG) after whole eye transplantation (WET) in a rodent model.
Methods: Syngeneic transplants were performed in nine Lewis rats. The donor flap consisted of all ocular tissue anterior to the optic chiasm, a section of temporal bone and the skin of the eyelid and external ear. A similar region of the orbital contents was removed in the recipient. The recipient optic nerve (ON) was cut at the base of the globe. Anastomoses of carotid arteries and external jugular veins were performed, as well as ON coaptation between donor and recipient. OCT was performed at one week after WET (n=7). Three weeks after WET, same animals received bilateral intravitreal injections of 1.5µL of 100mM manganese chloride (MnCl2) solution. Before and 1 day after MnCl2 injections, all animals were scanned using 9.4-Tesla/31-cm Varian/Agilent scanner to evaluate anterograde Mn transport along the visual pathway. ERG was performed at approximately seven weeks after WET to evaluate an electrical response in the retina from light stimuli in a separate subset of animals (n=2).
Results: OCT revealed visualization of all layers of the retina in the transplanted eyes. Two of the rats had opacities of the cornea and thus there was inability to visualize their retina. Results from MEMRI of the naïve (untransplanted) contralateral visual pathway showed significantly increased signal post-Mn injection in the left intraorbital (pre:102.3%±3.1%, post:191.0%±12.3%. These values are the MRI signal intensities of the visual system relative to a saline phantom.) and prechiasmatic ON (pre:116.4%±3.3%, post:221.3%±8.0%) and in the right lateral geniculate nucleus (LGN) (pre:116.1%±4.4%, post:170.2%±6.8%), and superior colliculus (SC) (pre:129.0%±3.0%, post:203.1%±6.0%), compared to pre-Mn injection (p<0.0001). MEMRI of the transplanted side revealed significantly increased signal post-Mn injection in the right donor intraorbital ON (pre:102.6%±2.4%, post:171.8%±13.0%) compared to pre-Mn injection (p<0.001). No apparent signal difference was observed between naïve (191.0%±12.3%) and transplanted (171.8%±13.0%) intraorbital ON post-Mn injection (p=0.26). No apparent signal intensity difference was observed between pre- and post-Mn injection in the right recipient prechiasmatic ON (pre:117.9%±4.8%, post:123.2%±4.5%), left LGN (pre:114.1%±4.7%, post:124.4%±5.2%) or left SC (pre:129.6%±3.5%, post:134.1%±3.2%) (p>0.05). ERG data revealed the presence of A and B waves in response to stimulating the retina with light in the transplanted eyes.
Conclusions: Qualitative analysis of OCT revealed that the structural integrity of the retina was relatively maintained after WET. MEMRI suggested the presence of anterograde Mn transport in the donor eye to the site of transection at approximately three weeks after WET. ERG data suggested some response to light stimuli in the photoreceptors of the transplanted eyes after WET. Viability of photoreceptors and retinal ganglion cells found in transplants
increases potential for optic nerve regeneration and restoration of vision with neuroregenerative therapies.
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