Low blood and vitreal BDNF, LXA4 and altered Th1/Th2 cytokine balance are potential risk factors for diabetic retinopathy

Kuppan, Kaviarasan; Mohanlal, Jithu; Mulla, Mohammad Arif; Sharma, Tarun; Shanmuganathan, Sivasankar; Das, Undurti N.; Angayarkanni, Narayanasamy

doi:10.1016/j.metabol.2015.04.005

Cited by 99 publications

(79 citation statements)

References 40 publications

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“…The lipoxins were the first identified and remain the only AA-derived SPMs. AA is the most abundant substrate for lipoxygenase enzymes in most tissues, and LXA 4 has been detected throughout the CNS (24, 47) and in human vitreous (48). Additionally, endogenous and aspirin-triggered lipoxins have been shown to reduce inflammatory pain processing through effects on astrocytes (49).…”

Section: Resultsmentioning

confidence: 99%

Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury

Livne‐Bar¹,

Wei²,

Liu³

et al. 2017

Journal of Clinical Investigation

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Section: Resultsmentioning

confidence: 99%

Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury

Livne‐Bar¹,

Wei²,

Liu³

et al. 2017

Journal of Clinical Investigation

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“…BDNF is also involved in the pathogenesis of obesity, type 2 diabetes mellitus and metabolic syndrome (42) (resveratrol) may have the ability to augment BDNF synthesis and action since BDNF also has similar beneficial actions in these diseases (42,46). In a recent study, we noted that BDNF levels are low in subjects with type 2 diabetes mellitus (47) and that it interacts and enhances the production of an anti-inflammatory bioactive lipid namely, lipoxin A4, whose levels are also low in diabetes mellitus (47)(48)(49). Lipoxin A4 is a potent suppressor of proinflammatory prostaglandin E2 synthesis (50).…”

Section: Resveratrol Is Cytoprotective In Naturementioning

confidence: 99%

“…Lipoxin A4 is a potent suppressor of proinflammatory prostaglandin E2 synthesis (50). This rises the interesting possibility that resveratrol may augment the production of lipoxin A4 and block that of prostaglandin E2 and thus, is able to bring about its beneficial actions in several diseases including autism, obesity, diabetes mellitus, metabolic syndrome, depression, schizophrenia and cancer (22,24,(43)(44)(45)(46)(47)(48)(49)(50)(51).…”

Section: Resveratrol Is Cytoprotective In Naturementioning

confidence: 99%

Beneficial action of resveratrol: How and why?

et al. 2016

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Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.

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“…In vitro experiments have established that RvE1and RvD1 are formed during retinal endothelial-PMN interactions and inhibit PMN transmigration and pro-inflammatory cytokines production [63]. A potential role of SPM circuits in human diabetic retinopathy is underscored by marked reduction of LXA 4 in the serum and vitreous humor with a concurrent increase of IL-6 in patients with diabetic retinopathy [64]. RvD1 formation has also been demonstrated in human endothelial cells in an in vitro model of diabetic retinopathy.…”

Section: Specialized Pro-resolving Mediators In Ocular Diseasesmentioning

confidence: 99%

“…It is important to recognize that 5-LOX is the key enzyme for amplifying and initiating inflammation but is also the rate-limiting and required enzyme for formation of the majority of SPM. Potential roles of SPM circuits in controlling innate immune responses in the retina are suggested by in vitro experiments that demonstrated LXA 4 's ability to inhibit LPS induced IL-6 production in human RPE cells [64]. …”

Section: Specialized Pro-resolving Mediators In Ocular Diseasesmentioning

confidence: 99%