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B.E. Brito, G. Bernal, O.A. Aguirre, L. Baute; Increased Susceptibility to LTA–Induced Uveitis During Hypercholesterolemia in Rabbits . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5072.
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Purpose: We previously reported that atherosclerosis–induced by high cholesterol serum levels increased eye susceptibility to local and systemic EIU in rabbits, showing significant increase in the number of inflammatory cells in aqueous humor. In this study, we investigated the susceptibility to Staphyloccocus aureus’ lipoteicoic acid (LTA) ad measured leukocyte infiltration (WBC) into the aqueous humor, as well as Tumor Necrosis Factor (TNF) and total protein (TP) levels in the aqueous humor. Methods: New Zealand white rabbits (3.5–4 Kg) fed with 0.3% cholesterol for 4 weeks and then with 0.1% for four more weeks dissolved in corn oil, or controls animals, were injected with 1 µg/ml S. aureus LTA intravitreally. Contalateral eye was injected with saline. Clinical observations were done by slit lamp and fotografic records. Aqueous humor was harvested after 24 h, and TNF activity was measured by WEHI 164 clone 13 bioassay, TP by a colorimetric assay and infiltrating WBC were also determined. Blood samples were taken to determined cholesterol levels by colorimetric assay. Aortas were sampled to determine the presence of atherosclerotic lesions. Results: The mean WBC in the aqueous humor in LTA injected eyes were significantly increased (p=0.014) in hypercholesterolemic rabbits (HChR, 9.01±4.05 x105 cells/ml, n=5) in comparison to control rabbits (CR, 3.97±0.6 x105 cells/ml, n=5). A significant difference (p=0.002) in TP concentration was observed in HChR ( 16.37±0.45 mg/dl, n=5) compared to CR (13,43±0.86 mg/dl, n=5). TNF levels were significantly higher (p=0.04) in HChR (1047±264.1 pg/ml, n=5) compared to CR (7.75±1.83 pg/ml, n=5). The percentage lesion area was (68.41±5.95 %, n=12) compared to CR where no lesions were observed. Cholesterol levels in HChR (715.17±25.14mg/dl, n=12) were significantly rised (p=0.004) versus CR (72.42±2.93mg/dl, n=11). Conclusions: As LPS, LTA also induced a stronger uveitis in those animals feed with hypercholesterolemic diets, which suggests an increased susceptibility to Gram–positive bacterias. The inflammatory eye response developed with the Gram–positive LTA local injection was not as strong the one can induced by Gram–negative lipopolysaccharide. TNF in HChR could be participating in increasing the blood–ocular barrier permeability allowing more leukocytes to infiltrate into the intraocular compartment during LTA–induced uveitis.
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