Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina

Retinal ganglion cells (RGCs) are the only output neurons of the vertebrate retina, integrating signals from other retinal neurons and transmitting information to the visual centers of the brain. The death of RGCs is a common outcome in many optic neuropathies, such as glaucoma, demyelinating optic...

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Main Authors: Farrah Blades, Vickie H. Y. Wong, Christine T. O. Nguyen, Bang V. Bui, Trevor J. Kilpatrick, Michele D. Binder
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-08-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2020.00840/full
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author Farrah Blades
Vickie H. Y. Wong
Christine T. O. Nguyen
Bang V. Bui
Trevor J. Kilpatrick
Michele D. Binder
Michele D. Binder
author_facet Farrah Blades
Vickie H. Y. Wong
Christine T. O. Nguyen
Bang V. Bui
Trevor J. Kilpatrick
Michele D. Binder
Michele D. Binder
author_sort Farrah Blades
collection DOAJ
description Retinal ganglion cells (RGCs) are the only output neurons of the vertebrate retina, integrating signals from other retinal neurons and transmitting information to the visual centers of the brain. The death of RGCs is a common outcome in many optic neuropathies, such as glaucoma, demyelinating optic neuritis and ischemic optic neuropathy, resulting in visual defects and blindness. There are currently no therapies in clinical use which can prevent RGC death in optic neuropathies; therefore, the identification of new targets for supporting RGC survival is crucial in the development of novel treatments for eye diseases. In this study we identify that the receptor tyrosine kinase, Tyro3, is critical for normal neuronal function in the adult mouse retina. The loss of Tyro3 results in a reduction in photoreceptor and RGC function as measured using electroretinography. The reduction in RGC function was associated with a thinner retinal nerve fiber layer and fewer RGCs. In the central retina, independent of the loss of RGCs, Tyro3 deficiency resulted in a dramatic reduction in the number of RGC dendrites in the inner plexiform layer. Our results show that Tyro3 has a novel, previously unidentified role in retinal function, RGC survival and RGC morphology. The Tyro3 pathway could therefore provide an alternative, targetable pathway for RGC protective therapeutics.
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spelling doaj.art-a75420c624ad493c93d1b8492dc2b3942022-12-21T20:36:15ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-08-011410.3389/fnins.2020.00840566209Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse RetinaFarrah Blades0Vickie H. Y. Wong1Christine T. O. Nguyen2Bang V. Bui3Trevor J. Kilpatrick4Michele D. Binder5Michele D. Binder6The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, AustraliaThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, AustraliaThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, AustraliaDepartment of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, AustraliaRetinal ganglion cells (RGCs) are the only output neurons of the vertebrate retina, integrating signals from other retinal neurons and transmitting information to the visual centers of the brain. The death of RGCs is a common outcome in many optic neuropathies, such as glaucoma, demyelinating optic neuritis and ischemic optic neuropathy, resulting in visual defects and blindness. There are currently no therapies in clinical use which can prevent RGC death in optic neuropathies; therefore, the identification of new targets for supporting RGC survival is crucial in the development of novel treatments for eye diseases. In this study we identify that the receptor tyrosine kinase, Tyro3, is critical for normal neuronal function in the adult mouse retina. The loss of Tyro3 results in a reduction in photoreceptor and RGC function as measured using electroretinography. The reduction in RGC function was associated with a thinner retinal nerve fiber layer and fewer RGCs. In the central retina, independent of the loss of RGCs, Tyro3 deficiency resulted in a dramatic reduction in the number of RGC dendrites in the inner plexiform layer. Our results show that Tyro3 has a novel, previously unidentified role in retinal function, RGC survival and RGC morphology. The Tyro3 pathway could therefore provide an alternative, targetable pathway for RGC protective therapeutics.https://www.frontiersin.org/article/10.3389/fnins.2020.00840/fullTAM receptorreceptor tyrosine kinaseselectroretinogramoptical coherence tomographydendritesinner plexiform layer
spellingShingle Farrah Blades
Vickie H. Y. Wong
Christine T. O. Nguyen
Bang V. Bui
Trevor J. Kilpatrick
Michele D. Binder
Michele D. Binder
Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
Frontiers in Neuroscience
TAM receptor
receptor tyrosine kinases
electroretinogram
optical coherence tomography
dendrites
inner plexiform layer
title Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
title_full Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
title_fullStr Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
title_full_unstemmed Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
title_short Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina
title_sort tyro3 contributes to retinal ganglion cell function survival and dendritic density in the mouse retina
topic TAM receptor
receptor tyrosine kinases
electroretinogram
optical coherence tomography
dendrites
inner plexiform layer
url https://www.frontiersin.org/article/10.3389/fnins.2020.00840/full
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