RESUMEN
No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Lipocalin 2 (LCN2 or NGAL), alone or complexed with MMP-9 (NGAL/MMP-9), is increased in several retinal disorders. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched healthy controls (n = 130). Samples with CRP > 5 mg/L, creatinine > 100 µmol/L, and/or urea > 7.5 mmol/L were excluded. Serum LCN2 was lower in CSCR patients than controls (81.4 ± 48.7 vs 107.3 ± 44.5 ng/ml, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.006). Serum NGAL/MMP-9 was lower in CSCR patients than controls (47.2 ± 40.7 vs 74.1 ± 42.6, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.002). A ROC curve showed that for LCN2 serum levels, the 80-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 80.3% sensitivity and 75.8% specificity, and for NGAL/MMP-9 serum levels, a 38-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 69.6% sensitivity and 80.3% specificity. In both acute and chronic CSCR, low serum LCN2 and NGAL/MMP-9, provide a biological link between the two CSCR forms, and potential susceptibility to oxidative stress and innate immune dysregulation in CSCR.
Asunto(s)
Biomarcadores/sangre , Coriorretinopatía Serosa Central/sangre , Lipocalina 2/sangre , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Curva ROC , Estudios RetrospectivosRESUMEN
The translocation t(12;22)(p13;q11) creates an MN1-TEL fusion gene leading to acute myeloid leukemia. MN1 is a transcription coactivator of the retinoic acid and vitamin D receptors, and TEL (ETV6) is a member of the E26-transformation-specific family of transcription factors. In MN1-TEL, the transactivating domains of MN1 are combined with the DNA-binding domain of TEL. We show that MN1-TEL inhibits retinoic acid receptor (RAR)-mediated transcription, counteracts coactivators such as p160 and p300, and acts as a dominant-negative mutant of MN1. Compared to MN1, the same transactivation domains in MN1-TEL are poorly stimulated by p160, p300 or histone deacetylase inhibitors, indicating that the block of RAR-mediated transcription by MN1-TEL is caused by dysfunctional transactivation domains rather than by recruitment of corepressors. The mechanism leading to myeloid leukemia in t(12;22) thus differs from the translocations that involve RAR itself.