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When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma

PURPOSE: Animal models show retinal ganglion cell (RGC) injuries that replicate features of glaucoma and the contralateral eye is commonly used as an internal control. There is significant crossover of RGC axons from the ipsilateral to the contralateral side at the level of the optic chiasm, which m...

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Autores principales: Tribble, James R., Kokkali, Eirini, Otmani, Amin, Plastino, Flavia, Lardner, Emma, Vohra, Rupali, Kolko, Miriam, André, Helder, Morgan, James E., Williams, Pete A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804521/
https://www.ncbi.nlm.nih.gov/pubmed/33510961
http://dx.doi.org/10.1167/tvst.10.1.22
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author Tribble, James R.
Kokkali, Eirini
Otmani, Amin
Plastino, Flavia
Lardner, Emma
Vohra, Rupali
Kolko, Miriam
André, Helder
Morgan, James E.
Williams, Pete A.
author_facet Tribble, James R.
Kokkali, Eirini
Otmani, Amin
Plastino, Flavia
Lardner, Emma
Vohra, Rupali
Kolko, Miriam
André, Helder
Morgan, James E.
Williams, Pete A.
author_sort Tribble, James R.
collection PubMed
description PURPOSE: Animal models show retinal ganglion cell (RGC) injuries that replicate features of glaucoma and the contralateral eye is commonly used as an internal control. There is significant crossover of RGC axons from the ipsilateral to the contralateral side at the level of the optic chiasm, which may confound findings when damage is restricted to one eye. The effect of unilateral glaucoma on neuroinflammatory damage to the contralateral pathway of RGC projections has largely been unexplored. METHODS: Ocular hypertensive glaucoma was induced unilaterally or bilaterally in the rat and RGC neurodegenerative events were assessed. Neuroinflammation was quantified in the retina, optic nerve head, optic nerve, lateral geniculate nucleus, and superior colliculus by high-resolution imaging, and in the retina by flow cytometry and protein arrays. RESULTS: After ocular hypertensive stress, peripheral monocytes enter the retina and microglia become reactive. This effect is more marked in animals with bilateral ocular hypertensive glaucoma. In rats where glaucoma was induced unilaterally, there was significant microglia activation in the contralateral (control) eye. Microglial activation extended into the optic nerve and terminal visual thalami, where it was similar across hemispheres in unilateral ocular hypertension. CONCLUSIONS: These data suggest that caution is warranted when using the contralateral eye as a control and in comparing visual thalami in unilateral models of glaucoma. TRANSLATIONAL RELEVANCE: The use of a contralateral eye as a control may confound the discovery of human-relevant mechanism and treatments in animal models. We also identify neuroinflammatory protein responses that warrant further investigation as potential disease-modifiable targets.
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spelling pubmed-78045212021-01-27 When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma Tribble, James R. Kokkali, Eirini Otmani, Amin Plastino, Flavia Lardner, Emma Vohra, Rupali Kolko, Miriam André, Helder Morgan, James E. Williams, Pete A. Transl Vis Sci Technol Article PURPOSE: Animal models show retinal ganglion cell (RGC) injuries that replicate features of glaucoma and the contralateral eye is commonly used as an internal control. There is significant crossover of RGC axons from the ipsilateral to the contralateral side at the level of the optic chiasm, which may confound findings when damage is restricted to one eye. The effect of unilateral glaucoma on neuroinflammatory damage to the contralateral pathway of RGC projections has largely been unexplored. METHODS: Ocular hypertensive glaucoma was induced unilaterally or bilaterally in the rat and RGC neurodegenerative events were assessed. Neuroinflammation was quantified in the retina, optic nerve head, optic nerve, lateral geniculate nucleus, and superior colliculus by high-resolution imaging, and in the retina by flow cytometry and protein arrays. RESULTS: After ocular hypertensive stress, peripheral monocytes enter the retina and microglia become reactive. This effect is more marked in animals with bilateral ocular hypertensive glaucoma. In rats where glaucoma was induced unilaterally, there was significant microglia activation in the contralateral (control) eye. Microglial activation extended into the optic nerve and terminal visual thalami, where it was similar across hemispheres in unilateral ocular hypertension. CONCLUSIONS: These data suggest that caution is warranted when using the contralateral eye as a control and in comparing visual thalami in unilateral models of glaucoma. TRANSLATIONAL RELEVANCE: The use of a contralateral eye as a control may confound the discovery of human-relevant mechanism and treatments in animal models. We also identify neuroinflammatory protein responses that warrant further investigation as potential disease-modifiable targets. The Association for Research in Vision and Ophthalmology 2021-01-12 /pmc/articles/PMC7804521/ /pubmed/33510961 http://dx.doi.org/10.1167/tvst.10.1.22 Text en Copyright 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Article
Tribble, James R.
Kokkali, Eirini
Otmani, Amin
Plastino, Flavia
Lardner, Emma
Vohra, Rupali
Kolko, Miriam
André, Helder
Morgan, James E.
Williams, Pete A.
When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma
title When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma
title_full When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma
title_fullStr When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma
title_full_unstemmed When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma
title_short When Is a Control Not a Control? Reactive Microglia Occur Throughout the Control Contralateral Pathway of Retinal Ganglion Cell Projections in Experimental Glaucoma
title_sort when is a control not a control? reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804521/
https://www.ncbi.nlm.nih.gov/pubmed/33510961
http://dx.doi.org/10.1167/tvst.10.1.22
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