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Arachidonic acid cascade and platelet-activating factor in the network of eye inflammatory mediators: therapeutic implications in uveitis

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Abstract

The cellular and biochemical events triggered by uveitis involve a complex array of cells and a heterogeneous network of mediators of intraocular inflammation. Resident cells are activated and inflammatory cells are recruited. Chemical mediators from the arachidonic acid cascade, prostaglandins, hydroxyeicosatetraenoic acids, and leukotrienes, are formed. Several of these metabolites are modulators of cellular functions, but when generated in sustained, excessive amounts, they contribute to enhanced vascular permeability and to the onset of pathophysiological responses. Another very active membrane-derived mediator is plateletactivating factor. This important mediator of immune and inflammatory responses may play a central role in uveitis due to cell priming, since interleukin-1, tumor necrosis factor, and other as yet unidentified mediators are also being generated. The concomitant accumulation of these networks of mediators in various parts of the uveal tract leads to spreading of the intraocular inflammatory response and cellular damage. At both early and late stages of uveitis, the generation of free radicals is also a major contributor to the impairment of function. Free radicals are generated in two distinct sites: in the oxidative burst of recruited white cells and in free radical formation and lipid peroxidation in resident cells. The identification of the cellular events that lead to the accumulation of networks of mediators of inflammation and their effects has important therapeutic implications in uveitis.

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Abbreviations

EAU:

experimental autoimmune uveitis

5-HETE, 12-HETE, 15-HETE:

5-,12-,15-hydroxyeicosatetraenoic acid

IL-1:

interleukin-1

LT:

leukotriene

PAF:

platelet-activating factor

PG:

prostaglandin

PMN:

polymorphonuclear leukocyte

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Louisiana State University, Eye Center and Neuroscience Center, 2020 Gravier Street, Suite B, Louisiana, USA

    Nicolas G. Bazan & Haydee E. P. Bazan

  2. Eye, Ear, Nose and Throat Hospital, 70112, New Orleans, Louisiana, USA

    Nicolas G. Bazan & Haydee E. P. Bazan

  3. Escola Paulista de Medicina, Sao Paulo-SP, Brazil

    Mariza Toledo de Abreu & Rubens Belfort Jr.

Authors
  1. Nicolas G. Bazan
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  2. Mariza Toledo de Abreu
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  3. Haydee E. P. Bazan
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  4. Rubens Belfort Jr.
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Bazan, N.G., de Abreu, M.T., Bazan, H.E.P. et al. Arachidonic acid cascade and platelet-activating factor in the network of eye inflammatory mediators: therapeutic implications in uveitis. Int Ophthalmol 14, 335–344 (1990). https://doi.org/10.1007/BF00163553

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