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Eleftherios I Paschalis, Elise Taniguchi, Alja Crnej, Kathryn Colby, Louis R Pasquale, James Chodosh, Claes H Dohlman, Lucy Q Shen, Boston Keratoprosthesis and Glaucoma Study Group; Tumor Necrosis Factor Alpha and Leptin Levels in Boston Keratoprosthesis Patients: Preliminary Data. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3735.
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Tumor necrosis factor alpha (TNF-α) is a pluripotent cytokine, which is up-regulated during wound healing and can mediate retinal ganglion cell (RGC) apoptosis and glaucoma. Recent reports suggest that Boston Keratoprosthesis (BKpro) patients are more likely to develop glaucomatous optic nerve damage, even with normal intraocular pressure (IOP). We hypothesize that the persistent corneal wound healing in BKpro subjects potentiates the up-regulation of TNF-α, which may explain the high prevalence of glaucoma in these patients. This study evaluated the levels of soluble TNF-α (sTNF-α), sTNFR-I and II receptors, and leptin, a neurotrophic factor, in the blood of patients with and without BKpro.
Venous blood of BKpro (n=7) and non-BKpro (n=9) patients was collected in the morning hours using EDTA tubes. sTNF-α, sTNFRs and leptin plasma levels were quantified using the enzyme-linked immunosorbent assay (ELISA). Other tests performed included: erythrocyte sedimentation rate (ESR), body mass index (BMI) and IOP. Patients with underlying inflammatory conditions were excluded from this study.
Median ± standard error of means for age (59±3.7 years), BMI (25±1.5), IOP (15±1 mmHg) and ESR (9±1.8mm/hr) were similar among the groups (p>0.07; Mann-Whitney test). Likewise, sTNF-α (1.4±0.2 ng/mL), sTNFR-I (911±55 ng/mL), sTNFR-II (2433±191 ng/mL) and leptin (18.463±5.679 pg/mL) levels were not statistically different (p>0.11) among the groups; however, the sTNF-α/sTNFR-I ratio was significantly higher in the BKpro group (0.0022) compared to the non-BKpro (0.0013; p=0.04).
In this preliminary study, sTNF-α to sTNFR-I ratio was elevated in BKpro patients. This elevation can be attributed to the persistent, subclinical, corneal wound healing, measurable in the blood plasma. The increase in ratio can result in inadequate inhibition of sTNF-α, and detrimental effects on retinal ganglion cells. Further evaluation of a larger sample size, with sub-classification of glaucoma patients, is currently underway.
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