What is it about?
We analyzed the contribution of microglial reactivity to early axonal and glial alterations of the optic nerve in a model of experimental glaucoma. We induced ocular hypertension in rats for different intervals (3, 6, 10 and 15 weeks). We counted the number of retinal ganglion cells, studied the axonal transport of fluorescent β‐subunit cholera toxin to different brain visual areas and analyzed axonal and glial parameters in the optic nerve. We found that at early stages of experimental glaucoma (6 weeks of ocular hypertension) the number of retinal ganglion cells was normal, but there was a reduction of the axonal transport to visual areas in the brain that could be mapped to the myelinated portion of the optic nerve, beyond the optic nerve head. The disruption in the axonal transport at the optic nerve was accompanied by a significant decrease in phosphorylated neurofilament heavy chain immunoreactivity (a biomarker for axonal injury) and luxol fast blue staining (sign of demyelination), and also by a significant increase in the immunoreactivity of microglial and astrocytic markers (glial response). At late stages (i.e 15 weeks), in addition to the axoglial alterations the number of retinal ganglion cells was significantly reduced. Finally, we treated rats with minocycline (30 mg/kg, i.p.) for 2 weeks after 4 weeks of ocular hypertension to study the role of microglia to the early axoglial dysfunction. Minocycline prevented the decrease in phosphorylated neurofilament heavy‐chain immunoreactivity and luxol fast blue staining, the glial response and the deficit in anterograde transport induced by 6 weeks of ocular hypertension.
Photo by Harpreet Singh on Unsplash
Why is it important?
This article supports the hypothesis that axon pathology initiates and does not follow retinal ganglion cell loss during glaucoma. If confirmed in the human condition, the significance of our work is important because it supports the targeting of microglial reactivity to prevent early axoglial alterations in the proximal optic nerve and consequently, to slow the progression of glaucoma.
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This page is a summary of: Involvement of microglia in early axoglial alterations of the optic nerve induced by experimental glaucoma, Journal of Neurochemistry, June 2017, Wiley, DOI: 10.1111/jnc.14070.
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Front Cover Image of the Journal of Neurochemistry (Volume 142, Issue 2)
Glaucoma is a leading cause of blindness, characterized by retinal ganglion cell loss and optic nerve (ON) damage, which at present has no cure. Our results indicate that targeting the ON microglial reactivity with the administration of minocycline can prevent early axoglial alterations in the proximal portion of the ON, and consequently, slow glaucoma progression. The photomicrograph shows the cholera toxin β-subunit (CTB)-staining pattern in the superior colliculus (SC) from an animal in which one eye was injected with vehicle (Veh, normotensive eye) and the contralateral eye received chondroitin sulfate (CS) for 6 weeks (hypertensive eye) in the anterior chamber. The staining represents the anterograde transport from the retina to the SC. CTB labeled the entire retinotopic projection to the stratum zonale and the stratum griseum superficiale, the most superficial layers of the superior colliculus, which received projections from the vehicle-injected eye, whereas a reduction in CTB staining was observed in the SC which received projections from glaucomatous eye that was hypertensive for 6 week.
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