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Role of Bioactive Sphingolipids in Inflammation and Eye Diseases

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The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1161))

Abstract

Inflammation is a common underlying factor in a diversity of ocular diseases, ranging from macular degeneration, autoimmune uveitis, glaucoma, diabetic retinopathy and microbial infection. In addition to the variety of known cellular mediators of inflammation, such as cytokines, chemokines and lipid mediators, there is now considerable evidence that sphingolipid metabolites also play a central role in the regulation of inflammatory pathways. Various sphingolipid metabolites, such as ceramide (Cer), ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), and lactosylceramide (LacCer) can contribute to ocular inflammatory diseases through multiple pathways. For example, inflammation generates Cer from sphingomyelins (SM) in the plasma membrane, which induces death receptor ligand formation and leads to apoptosis of retinal pigment epithelial (RPE) and photoreceptor cells. Inflammatory stress by reactive oxygen species leads to LacCer accumulation and S1P secretion and induces proliferation of retinal endothelial cells and eventual formation of new vessels. In sphingolipid/lysosomal storage disorders, sphingolipid metabolites accumulate in lysosomes and can cause ocular disorders that have an inflammatory etiology. Sphingolipid metabolites activate complement factors in the immune-response mediated pathogenesis of macular degeneration. These examples highlight the integral association between sphingolipids and inflammation in ocular diseases.

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Acknowledgements

This work was supported by National Eye Institute grants [EY022071, EY025256, EY021725], and grants from Foundation Fighting Blindness Inc., USA and Research to Prevent Blindness Inc., USA. The authors gratefully acknowledge the editorial help received from Dr. Dianna A. Johnson, Emeritus Professor, UTHSC and Richard C. Grambergs, UTHSC, Memphis, TN.

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  1. Department of Ophthalmology, University of Tennessee Health Science Center, UTHSC, Memphis, TN, USA

    Koushik Mondal & Nawajes Mandal

  2. Anatomy and Neurobiology, University of Tennessee Health Science Center, UTHSC, Memphis, TN, USA

    Nawajes Mandal

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  1. 431 Chemistry Building, Wayne State University, Detroit, MI, USA

    Kenneth V. Honn

  2. National Institutes of Health, Durham, NC, USA

    Darryl C. Zeldin

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Mondal, K., Mandal, N. (2019). Role of Bioactive Sphingolipids in Inflammation and Eye Diseases. In: Honn, K., Zeldin, D. (eds) The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases. Advances in Experimental Medicine and Biology, vol 1161. Springer, Cham. https://doi.org/10.1007/978-3-030-21735-8_14

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