TY - JOUR
T1 - In vivo MRI evaluation of anterograde manganese transport along the visual pathway following whole eye transplantation
AU - Komatsu, Chiaki
AU - van der Merwe, Yolandi
AU - He, Lin
AU - Kasi, Anisha
AU - Sims, Jeffrey R.
AU - Miller, Maxine R.
AU - Rosner, Ian A.
AU - Khatter, Neil J.
AU - Su, An Jey A.
AU - Schuman, Joel S.
AU - Washington, Kia M.
AU - Chan, Kevin C.
N1 - Funding Information:
This work was supported by The Office of the Assistant Secretary of Defense for Health Affairs under Award No. W81XWH-14–1–0421 and W81XWH-16–1–0775 (Arlington, Virginia, USA), VA Pittsburgh Healthcare Administration (Pittsburgh, Pennsylvannia, USA), National Institutes of Health P30-EY008098 and R01-EY028125 (Bethesda, Maryland, USA); Eye and Ear Foundation (Pittsburgh, Pennsylvania, USA); and unrestricted funds from Research to Prevent Blindness (New York, New York, USA) to University of Pittsburgh and NYU Langone Health Department of Ophthalmology .
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4/15
Y1 - 2022/4/15
N2 - 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. Keywords (Max 6): Anterograde transport, magnetic resonance imaging, manganese, neuroregeneration, optic nerve, whole-eye transplantation
AB - 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. Keywords (Max 6): Anterograde transport, magnetic resonance imaging, manganese, neuroregeneration, optic nerve, whole-eye transplantation
KW - Animals
KW - Contrast Media/metabolism
KW - Magnetic Resonance Imaging/methods
KW - Mammals
KW - Manganese/metabolism
KW - Optic Nerve/diagnostic imaging
KW - Rats
KW - Visual Pathways/diagnostic imaging
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U2 - 10.1016/j.jneumeth.2022.109534
DO - 10.1016/j.jneumeth.2022.109534
M3 - Article
C2 - 35202613
AN - SCOPUS:85124994777
VL - 372
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
M1 - 109534
ER -