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Fabio Bignami, Giulio Ferrari, Chiara Giacomini, Eleonora Capitolo, Linda Chaabane, Paolo Rama; Trigeminal ganglion inflammation following corneal injury. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1693.
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The cornea receives sensory innervation from the ophthalmic branch of the trigeminal ganglion (TG). Trigeminal nerve ablation is associated with neurotrophic keratitis in cornea. However, the effect of corneal nerve damage on the TG -and specifically on inflammation- has not been clarified yet.
A corneal alkali burn was created in the right eye of CD1 mice. After 4 and 8 days, mice were analyzed by in vivo MRI before and post iv. administration of USPIOs contrast (marker of macrophages) using a 7T scanner. To assess USPIOs uptake, T2 relaxation time distribution was analyzed in both left and right TG. After MRI analysis, longitudinal sections of the TG were stained for Prussian blue to detect USPIOs+cells and for inflammatory CD markers to characterize these infiltrating cells. On day 1, 4 and 8, Real-Time PCR analysis was performed to measure the expression of pro-inflammatory cytokines in the TG, also after 4 days of topical anti-inflammatory treatment with 0.2% dexamethasone, only in the alkali-burned eye.
The corneal alkali burn induced a significant CD45+leukocyte infiltration in the right TG after 4 (1.7 fold) and 8 (2.2 fold) days. This infiltration was prevalent in the anterior part of the TG on day 4. In vivo MRI follow-up showed an increase of USPIOs+macrophages in the right TG at both time points, specially on day 8 (2.2 fold). Specifically, USPIOs uptake was predominantly found in the anterior part of the right TG on day 4. The Prussian Blue+USPIOs+macrophages were observed only in the right TG, and showed a M2-phenotype (CD45+F4/80+CD206+). Alkali burn induced a significant time-dependent increase of pro-inflammatory cytokines (IL-1β, TNFα and VEGF-A) in both the TGs, but prevalent in the right TG. The expression of IL-1β and VEGF-A were significantly reduced in the right TG following corneal treatment with dexamethasone.
Our findings support the involvement of brain structures (i.e. TG) after ocular surface damage: a corneal injury is able (i) to induce infiltration of leukocytes, in particular of M2-macrophages, in the TG and (ii) to increase pro-inflammatory cytokines in the TG; (iii) this inflammation was attenuated following anti-inflammatory therapy in the cornea. These results have relevant implication in understanding the pathophysiology and, potentially, in the treatment of many ocular ailments.
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