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This article is the author's final published version in PLoS One, Volume 18, Issue 4, Article number e0284082.

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The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as vascular remodeling characterized by alterations in vascular smooth muscle cell (VSMC) morphology, reduced blood vessel VSMC coverage, endothelial cell expression of the fibroblast specific protein 1, and significant increase in the number of podoplanin-positive lymphatic sprouts. Intriguingly, the deficiency of a major extracellular matrix component, small leucine-rich proteoglycan decorin, modifies both the direction and the extent of these changes. As the dura mater is the most important route for the brain metabolic clearance, these results are of clinical relevance and provide a much-needed link explaining the association between ophthalmic conditions and the development of neurodegenerative diseases.

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This work is licensed under a Creative Commons Public Domain Dedication 1.0 License.

journal.pone.0284082.s001.pdf (953 kB)
S1 Fig. Dura mater stromal and vascular responses to alkaline corneal injury

journal.pone.0284082.s002.pdf (769 kB)
S2 Fig. Dura mater stromal and vascular responses to alkaline corneal injury

journal.pone.0284082.s003.pdf (360 kB)
S3 Fig. Dura mater stromal and vascular responses to alkaline corneal injury

journal.pone.0284082.s004.xlsx (20 kB)
S1 File. FSP1, LYVE1 fluorescence intensity, PDPL+ sprout, LYVE1+ cell counts

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