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Haiyan Wang; Crosslink between lipids and uveitis: a lipidomic analysis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5758.
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We try to explore the roles of a variety of phospholipids and sphingolipids in the inflammatory process of uveitis.
Experiments were conducted in Endotoxin-induced uveitis (EIU) rat model. Aqueous humor (AH) and retina were obtained from control and EIU rats. Lipids were extracted and then subjected to mass spectrometric identification and ratiometric quantification. Relative intensity analysis (EIU/control) was performed to evaluate the amount change of common lipids between EIU and control groups.
EIU rat model was successfully established according to clinical, biochemical, and histological evaluation. Increase in total sphingolipids and phospholipids was observed in EIU AH and retina. Unique lipid species were found in control as well as in EIU AH and retina. Several phospholipid and sphingolipid species were found common to both groups but with remarkable differences in amount in individual group. Commensurate with significant increased level of lysophospholipids in EIU AH and retina, the ratio of lysophospholipids to total phospholipids was found significantly increased too. Further study revealed that PIs, regarded as immune homeostasis maintainer, remarkably increased in EIU AH by 2.3-fold and EIU retina by 4.2-fold. Pro-inflammatory factor PGs showed noteworthy increase in EIU AH by 1.5-fold and EIU retina by 8.0-fold. We also detected a significant increase of 18:0 lysophosphatidylcholine, which can activate G protein-coupled receptor G2A-mediated leukocyte response, in EIU group (fold change=6.4 in AH and 3.8 in retina). Cer240, Cer241, and SM240 remarkably increased in EIU AH. Concurrently the amount of total sphingolipids also significantly increase in EIU retina by 2.8- fold change, especially with increased C12 C-1-P, C16 C-1-P, C24 C-1-P, upregulated Cer160, Cer240, SM120, and SM240. Signaling molecule C-1-P is believed to transfer inflammation to homeostasis restoration by inhibiting NF-κB activation. However we still found elevated NF-κB in EIU retina, indicating that this level of enhancement in endogenous C-1-P cannot reverse the inflammation process induced by LPS.
Taken together, specific lipids might have exert function in EIU inflammation. Exogenous topical application of these protective lipids or inhibition of these pro-inflammatory lipids may be useful therapeutic strategies for the resolution of EIU. And the underlying mechanism deserves further study
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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