Friday, October 6, 2023

Neurology/Neuroscience Research Seminar

12:00 PM to 1:00 PM

BSRB room 5515

CME credit is available, click here

Attendance must be registered within 6 months of attendance to be awarded credit.

Recorded archives of live activities are considered enduring materials.

Viewing of a recorded session is for reference only, no CME credit can be claimed.

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Following injury, axons in the adult mammalian optic nerve fail to regenerate spontaneously, resulting in permanent functional deficits. Inflammation in the vitreous humor, triggered by intraocular administration of β-glucan, creates an immune milieu that strongly supports regeneration of severed retinal ganglion cell (RGC) axons. Unfortunately, the pro-regenerative effects are undermined by collateral damage caused by an overactive immune system. Here, we demonstrate that ocular infiltration of immune cells causes damage to the retinal vasculature and compromises the integrity of the blood-retina barrier (BRB). Microglia protect the inflamed vasculature, mitigate infiltration of hematogenous immune cells, and support RGC regeneration. Functional ablation of integrin alphaM (CD11b) attenuates β-glucan-elicited vitreal inflammation, protects the BRB, and strongly enhances RGC axon regeneration. Direct targeting of neutrophils with anti-Ly6G attenuates their accumulation in retinal venules and entry in the eye, preserves the BRB integrity, and enhances RGC regenerative growth. Moreover, the pro-regenerative effects of anti-Ly6G are sensitive to microglia depletion. Multiomics analysis of the ocular immune milieu revealed that manipulations reducing the trafficking of hematogenous immune cells do not alter their inflammatory states but effectively reduce vascular damage. Consequently, our study reveals that microglia play a vital role in protecting the inflamed BRB, and immune-mediated RGC regeneration is primarily hindered by neutrophil-elicited vascular damage. These findings unveil a previously unknown function of vascular inflammation in CNS axon regeneration.

“Immune Strategies for Central Nervous System Regeneration”

Roman Giger, Ph.D.

Dr Richard Mark Newman Research Professor of Cell and Developmental Biology
Professor of Cell and Developmental Biology
Professor of Neurology