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The potential of lipid mediator networks as ocular surface therapeutics and biomarkers.

ABSTRACT: In the last twenty years an impressive body of evidence in diverse inflammatory animal disease models and human tissues, has established polyunsaturated fatty acids (PUFA) derived specialized-pro-resolving mediators (SPM), as essential mediators for controlling acute inflammation, immune responses, wound healing and for resolving acute inflammation in many non-ocular tissues. SPM pathways and receptors are highly expressed in the ocular surface where they regulate wound healing, nerve regeneration, innate immunity and sex-specific regulation of auto-immune responses. Recent evidence indicates that in the eye these resident SPM networks are important for maintaining ocular surface health and immune homeostasis. Here, we will review and discuss evidence for SPMs and other PUFA-derived mediators as important endogenous regulators, biomarkers for ocular surface health and disease and their therapeutic potential.

SUBMITTER: Flitter BA

PROVIDER: S-EPMC7606340 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The potential of lipid mediator networks as ocular surface therapeutics and biomarkers.

Flitter Becca A BA Fang Xiaohui X Matthay Michael A MA Gronert Karsten K

The ocular surface 20200429

In the last twenty years an impressive body of evidence in diverse inflammatory animal disease models and human tissues, has established polyunsaturated fatty acids (PUFA) derived specialized-pro-resolving mediators (SPM), as essential mediators for controlling acute inflammation, immune responses, wound healing and for resolving acute inflammation in many non-ocular tissues. SPM pathways and receptors are highly expressed in the ocular surface where they regulate wound healing, nerve regenerati ...[more]

PMID: 32360792

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Project description:PurposePseudoexfoliation (PXF) is a unique form of glaucoma characterized by accumulation of exfoliative material in the eyes. Changes in tear profile in disease stages may give us insights into molecular mechanisms involved in causing glaucoma in the eye.MethodsAll patients were categorized into three main categories; pseudoexfoliation (PXF), pseudoexfoliation glaucoma (PXG) and cataract, which served as control. Cytokines, transforming growth factor β1 (TGFβ1), matrix metalloproteases (MMPs) and fibronectin (FN1) were assessed with multiplex bead assay, enzyme-linked immunosorbent assay (ELISA), gelatin zymography, and immunohistochemistry (IHC) respectively in different ocular tissues such as tears, tenon's capsule, aqueous humor (AH) and serum samples of patients with PXF stages.ResultsWe found that TGFβ1, MMP-9 and FN1 protein expression were upregulated in tears, tenon's capsule and AH samples in PXG compared to PXF, though the MMP-9 protein activity was downregulated in PXG compared with control or PXF. We have also found that in PXG tears sample the fold change of TGF-α (Transforming Growth Factor-α), MDC (Macrophage Derived Chemokine), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor) were significantly downregulated and the levels of GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IP-10 (Interferon- γ produced protein-10) were significant upregulated. While in AH; IL-6 (Interleukin-6), IL-8, VEGF, IFN-a2 (Interferon- α2), GRO (Growth regulated alpha protein) levels were found lower and IL1a (Interleukin-1α) level was higher in PXG compared to PXF. And in serum; IFN-a2, Eotaxin, GM-CSF, Fractalkine, IL-10 (Interleukin-10), IL1Ra (Interleukin-1 receptor antagonist), IL-7 (Interleukin-7), IL-8, MIP1β (Macrophage Inflammatory Protein-1β), MCP-1 (Monocyte Chemoattractant Protein-1) levels were significantly upregulated and PDGF-AA (Platelet Derived Growth Factor-AA) level was downregulated in the patients with PXG compared to PXF.ConclusionsAltered expression of these molecules in tears may therefore be used as a signal for onset of glaucoma or for identifying eyes at risk of developing glaucoma in PXF.

Dataset Information

The potential of lipid mediator networks as ocular surface therapeutics and biomarkers.

Publications

The potential of lipid mediator networks as ocular surface therapeutics and biomarkers.

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