Microglial Autofluorescence in the Brain and Retina is Dynamically Modulated by Systemic Inflammation

TL;DR

Systemic inflammation changes microglial autofluorescence in the brain and retina, but the patterns differ between regions, suggesting a complex relationship.

Contribution

The study reveals that retinal microglial autofluorescence reflects brain inflammation but with region-specific dynamics.

Findings

LPS-induced inflammation increased autofluorescent aggregates in brain microglia but reduced their total volume.

Retinal microglia showed similar but not identical autofluorescence changes compared to the brain.

Microglia in the brain and retina accumulate autofluorescent material differently during inflammation.

Abstract

The retina—an extension of the central nervous system—contains microglia that survey and respond to injury or pathogens. In response to their environmental milieu, these cells accumulate autofluorescent material likely reflective of cellular debris. Measuring these autofluorescence changes may be a useful tool for early diagnosis of brain-related inflammatory conditions or diseases by imaging the eye. To assess this, we gave Wistar rats a systemic immune challenge with lipopolysaccharide (LPS; 250 µg/kg, intraperitoneally) and examined autofluorescence characteristics of the microglia in brain and eye using confocal microscopy. Initial flow cytometry experiments verified that isolated microglia are highly autofluorescent compared to cells in immune-related organs such as spleen. In immunolabelled brain sections (arcuate, hippocampus, retrosplenial cortex), astrocytes, neurons, and microglia all displayed significant autofluorescence, with microglia displaying greatest levels. LPS led to predicted changes in microglial morphology in the brain and this was accompanied by an increase in the number of individual autofluorescent aggregates but a reduction in the total volume, indicative of changes in the dynamics of the material. While there were similarities in the microglial response to LPS in the retina, and the total volume of autofluorescence aggregates was also reduced, retinal autofluorescence changes did not simply predict those seen in brain. These findings suggest that the relationship between immune challenge states and autofluorescence accumulation is dynamic and complex. Understanding the role of microglia in accumulating and metabolising this autofluorescent material may assist our understanding of disease states and how they influence retina and brain.

We hypothesized that brain autofluorescence would change with inflammation and this would be reflected in similar changes detectable in retina. We found inflammation-associated autofluorescence changes in both brain and retina but that the dynamics of this differ depending upon region

We hypothesized that brain autofluorescence would change with inflammation and this would be reflected in similar changes detectable in retina. We found inflammation-associated autofluorescence changes in both brain and retina but that the dynamics of this differ depending upon region

The online version contains supplementary material available at 10.1007/s10571-026-01704-y.

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