Description
Experimental Autoimmune Uveitis (EAU) is a murine model of non-infectious posterior uveitis characterised by inflammation of the posterior segment, including the retina and ON. In this study, we characterised microglial cells within the optic nerve (ON) at early (e; 2–3 weeks post-immunisation, wPI) and late (l; 4–6 wPI) EAU phases using IBA1 as a marker of microglia and P2RY12 as a marker of surveillant microglia. C57Bl/6 mice (5–7 weeks) were immunised with IRBP1–20 in CFA s.c. with pertussis i.p.; controls received CFA/pertussis only. Weekly Micron V fundoscopy (EAU: n = 6–18 eyes; controls: n = 5–15 per time point) revealed significant optic disc inflammation (p < 0.01 at 2 wPI; p < 0.001 at 5 wPI; p < 0.0001 at 3, 4, 6 wPI), retinal vessel inflammation (p < 0.01 at 3–6 wPI), and retinal structural damage (p < 0.01 at 3, 5, 6 wPI; p < 0.001 at 4 wPI) vs. controls. Longitudinal ON cryosections (10 μm) were immunolabelled and analysed (e-SHAM = 8; l-SHAM = 9; e-EAU = 9; l-EAU = 12). IBA1 staining showed a higher number of morphologically activated microglia in e-EAU vs. e-SHAM (p < 0.05) and l-EAU (p < 0.05), suggesting a transient early inflammatory role. P2RY12 expression did not differ across groups, suggesting the surveillant microglia population remains stable. The data suggest that ON microglial activation is an early response of EAU pathogenesis. Future work could investigate the retina to define temporal differences in EAU-induced microglial activation.
Lay Abstract
Non-infectious posterior uveitis is an eye condition that affects people of all ages, where parts of the eye become inflamed, which can cause pain and damaged vision. There are cells in our nervous system called microglia that act like security guards, that monitor the environment and react when something goes wrong. Our research characterised these cells in the optic nerve, which sends visual information from the back of the eye (called the retina) to the brain. We scanned the eyes of mice with a condition that resembles uveitis-like features to track inflammation and damage. We also characterised microglia in the optic nerve through the microscope, at early and late stages of the disease. The results showed clear signs of uveitis-associated inflammation and damage in the modelled mice. Also, microglia in the optic nerve became more active during the early stages, but this activity dropped off later, suggesting that they may contribute to stimulating early inflammation in this model of uveitis. Future research could look at whether the same pattern occurs in the retina itself, which might reveal new opportunities for early treatment.
| Lay Title | Immune Cells in the Optic Nerve During an Inflammatory Eye Disease |
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| Role | PhD Student |