Chiaki Komatsu1, Yolandi van der Merwe2, Lin He3, Anisha Kasi4, Jeffrey R Sims4, Maxine R Miller5, Ian A Rosner1, Neil J Khatter6, An-Jey A Su7, Joel S Schuman8, Kia M Washington9, Kevin C Chan10. 1. Department of Plastic and Reconstructive Surgery, Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States. 2. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 3. Department of Plastic and Reconstructive Surgery, Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States; Department of Plastic, Aesthetic & Maxillofacial Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. 4. Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, United States. 5. Department of Plastic and Reconstructive Surgery, Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 6. Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Colorado, Denver, CO, United States; William Beaumont School of Medicine, Oakland University, Rochester, MI, United States. 7. Department of Plastic and Reconstructive Surgery, Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States; Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Colorado, Denver, CO, United States. 8. Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, United States; Neuroscience Institute, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, United States; Center for Neural Science, College of Arts and Science, New York University, New York, NY, United States; Department of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States. 9. Department of Plastic and Reconstructive Surgery, Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Colorado, Denver, CO, United States; Veterans Administration Pittsburgh Healthcare System, Pittsburgh, PA, United States. 10. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, United States; Neuroscience Institute, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, United States; Center for Neural Science, College of Arts and Science, New York University, New York, NY, United States; Department of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY, United States; Department of Radiology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, United States. Electronic address: chuenwing.chan@fulbrightmail.org.
Abstract
BACKGROUND: Since adult mammalian retinal ganglion cells cannot regenerate after injury, we have recently established a whole-eye transplantation (WET) rat model that provides an intact optical system to investigate potential surgical restoration of irreversible vision loss. However, it remains to be elucidated whether physiological axoplasmic transport exists in the transplanted visual pathway. NEW METHOD: We developed an in vivo imaging model system to assess WET integration using manganese-enhanced magnetic resonance imaging (MEMRI) in rats. Since Mn2+ is a calcium analogue and an active T1-positive contrast agent, the levels of anterograde manganese transport can be evaluated in the visual pathways upon intravitreal Mn2+ administration into both native and transplanted eyes. RESULTS: No significant intraocular pressure difference was found between native and transplanted eyes, whereas comparable manganese enhancement was observed between native and transplanted intraorbital optic nerves, suggesting the presence of anterograde manganese transport after WET. No enhancement was detected across the coaptation site in the higher visual areas of the recipient brain. COMPARISON WITH EXISTING METHODS: Existing imaging methods to assess WET focus on either the eye or local optic nerve segments without direct visualization and longitudinal quantification of physiological transport along the transplanted visual pathway, hence the development of in vivo MEMRI. CONCLUSION: Our established imaging platform indicated that essential physiological transport exists in the transplanted optic nerve after WET. As neuroregenerative approaches are being developed to connect the transplanted eye to the recipient's brain, in vivo MEMRI is well-suited to guide strategies for successful WET integration for vision restoration.
BACKGROUND: Since adult mammalian retinal ganglion cells cannot regenerate after injury, we have recently established a whole-eye transplantation (WET) rat model that provides an intact optical system to investigate potential surgical restoration of irreversible vision loss. However, it remains to be elucidated whether physiological axoplasmic transport exists in the transplanted visual pathway. NEW METHOD: We developed an in vivo imaging model system to assess WET integration using manganese-enhanced magnetic resonance imaging (MEMRI) in rats. Since Mn2+ is a calcium analogue and an active T1-positive contrast agent, the levels of anterograde manganese transport can be evaluated in the visual pathways upon intravitreal Mn2+ administration into both native and transplanted eyes. RESULTS: No significant intraocular pressure difference was found between native and transplanted eyes, whereas comparable manganese enhancement was observed between native and transplanted intraorbital optic nerves, suggesting the presence of anterograde manganese transport after WET. No enhancement was detected across the coaptation site in the higher visual areas of the recipient brain. COMPARISON WITH EXISTING METHODS: Existing imaging methods to assess WET focus on either the eye or local optic nerve segments without direct visualization and longitudinal quantification of physiological transport along the transplanted visual pathway, hence the development of in vivo MEMRI. CONCLUSION: Our established imaging platform indicated that essential physiological transport exists in the transplanted optic nerve after WET. As neuroregenerative approaches are being developed to connect the transplanted eye to the recipient's brain, in vivo MEMRI is well-suited to guide strategies for successful WET integration for vision restoration.
Authors: Stefanie Fischer; Christian Engelmann; Karl-Heinz Herrmann; Jürgen R Reichenbach; Otto W Witte; Falk Weih; Alexandra Kretz; Ronny Haenold Journal: J Vis Exp Date: 2014-07-22 Impact factor: 1.355
Authors: Yolandi van der Merwe; Matthew C Murphy; Jeffrey R Sims; Muneeb A Faiq; Xiao-Ling Yang; Leon C Ho; Ian P Conner; Yu Yu; Christopher K Leung; Gadi Wollstein; Joel S Schuman; Kevin C Chan Journal: Neurotherapeutics Date: 2021-04-13 Impact factor: 7.620
Authors: D M Sudarshana; G Nair; J T Dwyer; B Dewey; S U Steele; D J Suto; T Wu; B A Berkowitz; A P Koretsky; I C M Cortese; D S Reich Journal: AJNR Am J Neuroradiol Date: 2019-08-01 Impact factor: 3.825