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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2021
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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. |
format | Online Article Text |
id | pubmed-7804521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
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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