When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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.

In: Translational Vision Science and Technology, Vol. 10, 22, 2021, p. 1-23.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tribble, JR, Kokkali, E, Otmani, A, Plastino, F, Lardner, E, Vohra, R, Kolko, M, André, H, Morgan, JE & Williams, PA 2021, 'When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma', Translational Vision Science and Technology, vol. 10, 22, pp. 1-23. https://doi.org/10.1167/tvst.10.1.22

APA

Tribble, J. R., Kokkali, E., Otmani, A., Plastino, F., Lardner, E., Vohra, R., Kolko, M., André, H., Morgan, J. E., & Williams, P. A. (2021). When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma. Translational Vision Science and Technology, 10, 1-23. [22]. https://doi.org/10.1167/tvst.10.1.22

Vancouver

Tribble JR, Kokkali E, Otmani A, Plastino F, Lardner E, Vohra R et al. When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma. Translational Vision Science and Technology. 2021;10:1-23. 22. https://doi.org/10.1167/tvst.10.1.22

Author

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. In: Translational Vision Science and Technology. 2021 ; Vol. 10. pp. 1-23.

Bibtex

@article{22f0e6f19c514626b35ab16fed58a1c9,
title = "When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma",
abstract = "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.",
keywords = "Glaucoma, Lateral geniculate nucleus, Microglia, Monocyte, Neuroinflammation, Optic nerve, Optic nerve head, Retina, Superior colliculus",
author = "Tribble, {James R.} and Eirini Kokkali and Amin Otmani and Flavia Plastino and Emma Lardner and Rupali Vohra and Miriam Kolko and Helder Andr{\'e} and Morgan, {James E.} and Williams, {Pete A.}",
year = "2021",
doi = "10.1167/tvst.10.1.22",
language = "English",
volume = "10",
pages = "1--23",
journal = "Translational Vision Science & Technology",
issn = "2164-2591",
publisher = "Association for Research in Vision and Ophthalmology",

}

RIS

TY - JOUR

T1 - When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma

AU - Tribble, James R.

AU - Kokkali, Eirini

AU - Otmani, Amin

AU - Plastino, Flavia

AU - Lardner, Emma

AU - Vohra, Rupali

AU - Kolko, Miriam

AU - André, Helder

AU - Morgan, James E.

AU - Williams, Pete A.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Glaucoma

KW - Lateral geniculate nucleus

KW - Microglia

KW - Monocyte

KW - Neuroinflammation

KW - Optic nerve

KW - Optic nerve head

KW - Retina

KW - Superior colliculus

U2 - 10.1167/tvst.10.1.22

DO - 10.1167/tvst.10.1.22

M3 - Journal article

C2 - 33510961

AN - SCOPUS:85099841345

VL - 10

SP - 1

EP - 23

JO - Translational Vision Science & Technology

JF - Translational Vision Science & Technology

SN - 2164-2591

M1 - 22

ER -

ID: 256211511