The role of pro-resolving lipid mediators in ocular diseases

Wei, Jessica; Gronert, Karsten

doi:10.1016/j.mam.2017.03.006

Cited by 22 publications

(25 citation statements)

References 69 publications

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“…Docosahexaenoic acid (DHA) is the most abundant and terminal ɷ−3 PUFA and it is highly enriched in the brain, retina and testis. The protective actions of dietary DHA in part have been attributed to formation of specialized pro-resolving lipid mediators (SPM), namely resolvins, protectins and maresins 7–10 . These SPM are generated primarily by the coordinated interaction of 5-lipoxygenase (LOX) and 12/15-LOX, two enzymes that are also essential for the formation of the founding member of the SPM family 11 , namely the eicosanoid lipoxin A 4 (LXA 4 ), which is an arachidonic acid (ɷ−6 PUFA) product.…”

Section: Introductionmentioning

confidence: 99%

Dietary DHA amplifies LXA4 circuits in tissues and lymph node PMN and is protective in immune-driven dry eye disease

Gao

Zhang

et al. 2018

Mucosal Immunology

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Recently identified regulatory PMN control immune-driven dry eye disease (DED) in females by producing the arachidonic acid (ω-6)-derived specialized pro-resolving mediator (SPM), LXA, in lymph nodes. Dietary ω-3 docosahexaenoic acid (DHA) is protective in DED but mechanisms of action remain elusive. DHA is converted to ω-3 SPMs by PMN via the same lipoxygenases (LOX) that generate LXA. We investigated if dietary DHA amplifies SPM formation and affects T effector cell function and/or regulatory PMN in DED. DED was induced in mice on a DHA-enriched or ω-3-deficient diet. DHA deficiency amplified DED with marked sex-specific differences. Dietary DHA protection against dry eye disease correlated with increased PMN levels in lymph nodes, ocular tissues, and unexpectedly, selective amplification of LXA tissue levels. Dietary DHA increased 12/15-LOX and decreased 5-LOX expression in lymph nodes and isolated lymph node PMN, which correlated with amplified LXA formation. Acute DHA treatment rescued DHA-deficient females from exaggerated DED by amplifying lymph node LXA formation, increasing T and decreasing T1 and T17 effector cells. Our results identify DHA regulation of LXA producing PMN in ocular tissues and lymph nodes in health and immune disease as novel mechanism and determinant for T-cell responses to routine ocular injury or stress signals.

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Section: Introductionmentioning

confidence: 99%

Dietary DHA amplifies LXA4 circuits in tissues and lymph node PMN and is protective in immune-driven dry eye disease

Gao

Zhang

et al. 2018

Mucosal Immunology

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“…As for the brain, LX and LOX activities in the eye have been primarily studied in the context of ocular inflammation, wound repair and angiogenesis . However, we reported that LXA 4 and LXB 4 are produced by retinal astrocytes and are regulated under stress.…”

Section: Lipoxins Can Mediate Direct Neuronal Actionsmentioning

confidence: 95%

“…As for the brain, LX and LOX activities in the eye have been primarily studied in the context of ocular inflammation, wound repair and angiogenesis. [91][92][93] However, we reported that LXA 4 and LXB 4 are produced by retinal astrocytes and are regulated under stress. Both LXs are detected in mouse retina and optic nerve, but their levels and 5-LOX expression decrease following injury.…”

Section: Lipoxins Can Mediate Direct Neuronal Actionsmentioning

confidence: 99%

Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

Kim

Livne‐Bar

Gronert

et al. 2020

Molecular Nutrition Food Res

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Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)–metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega‐6 PUFA. In addition to well‐established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.

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“…Recent reports have demonstrated that lipoxins are not only formed during inflammation and the resolution phase of inflammation, but that they are also part of normal signaling in healthy tissues and actively regulate homeostasis and the threshold for activation of immune responses in the cornea, lymph nodes, lacrimal glands and retina [11,12,19,20]. Regulation and therapeutic amplification of this homeostatic SPM circuit in health and diseases is the focus of several NIH-funded projects.…”

Section: Lxa 4 Regulation Of Lymphoid-derived Cellsmentioning

confidence: 99%

Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells

Wei

Gronert

2019

Trends in Biochemical Sciences

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Eicosanoids and specialized proresolving mediators (SPM) regulate leukocyte function and inflammation. They are ideally positioned at the interphase of innate and adaptive immune responses when lymphocytes interact with leukocytes. Receptors for LTB4, PGE2 and SPM are expressed in lymphocytes. Evidence points toward an essential role of these lipid mediators for directly regulating lymphocyte functions. SPMs, which include lipoxins, demonstrate comprehensive protective actions with lymphocytes. LTB4 and PGE2 regulation of lymphocyte is diverse and depends on the interaction of lymphocytes with other cells. Importantly, both LTB4 and PGE2 are essential regulators of T cell anti-tumor activity. These lipid mediators are attractive therapeutic targets to control dysregulated innate and adaptive immune responses, promote lymphocyte antitumor activity and prevent tumor immune evasion.

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The role of pro-resolving lipid mediators in ocular diseases

Cited by 22 publications

References 69 publications

Dietary DHA amplifies LXA4 circuits in tissues and lymph node PMN and is protective in immune-driven dry eye disease

Dietary DHA amplifies LXA4 circuits in tissues and lymph node PMN and is protective in immune-driven dry eye disease

Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells

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