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N. Kociok, S. Winterhalter, A. M. Joussen; Altered mRNA Expression of Angiogenic Factors and Tight-Junction Proteins in Endotoxin-Induced Uveitis in the Rat Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3893. doi: https://doi.org/.
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Uveitis is one of the leading causes of blindness. Endotoxin-induced uveitis is an acute intraocular inflammatory condition that mimics human disease and is induced in an animal model by the injection of sub lethal doses of lipopolysaccharide (LPS). Exposure to LPS stimulates cellular inflammatory responses like the release of cytokines such as VEGF and interleukins. Occludin and claudin-1 are tight junction proteins that play a major role in maintaining the blood-retinal barrier in vivo. Here we evaluated the influence of the release of pro-inflammatory cytokines on the mRNA expression of angiogenic factors and tight-junction proteins.
Long Evans rats received a footpad injection of 200 µg/kg body weight LPS from Salmonella typhimurium in phosphate-buffered saline (PBS) or PBS alone. The eyes were enucleated, RNA was isolated from the retinas and reverse transcribed. The mRNA expression of the analyzed genes in the retina of uveitic rats and their controls was quantified by Real-Time RT-PCR.
The mRNA level of TNFα, ICAM-1, VEGF, angiopoietin 1 and 2, occludin, and claudin-1 was quantified in the retinas of LPS-induced uveitic rats and non-uveitic controls. In the retinas of uveitic rats elevated mRNA levels (2-fold to 200-fold) were measured for most of the analyzed genes as compared to non-uveitic controls except for VEGF and occludin. Here the mRNA expression remained constant or was reduced 2-fold, respectively.
From these data we conclude an active influence of pro-inflammatory cytokines on the expression of angiogenic factors and tight-junction proteins in uveitis. Modulating the expression of pro and anti-inflammatory factors or the cognate receptors and stabilizing tight-junction proteins could become a potential therapeutic strategy for inhibiting uveitis.
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