Retinoblastoma: hacia un diagnóstico más precoz / Retinoblastoma: towards an earlier diagnosis

OBJETIVOS: El número de enucleaciones y secuelas visuales por retinoblastoma es elevado. El objetivo del estudio fue evaluar diferentes aspectos diagnósticos y plantear estrategias que ayuden a mejorar el manejo clínico del retinoblastoma. Método: Estudio retrospectivo de 38 pacientes con retinoblastoma estudiados genéticamente (29 unilaterales, 9 bilaterales). Se evaluaron la edad de inicio, los signos clínicos y el tiempo de evolución, el número de enucleaciones, el momento de realización y la supervivencia a 5 años. Resultados: La leucocoria fue el signo clínico fundamental (presente en el 90% de los casos). El retraso diagnóstico medio fue de 3,2 meses. Entre los casos unilaterales se enuclearon el 76% de los ojos y en las formas bilaterales el 55%. Solo se encontró un fallecimiento entre los 25 pacientes seguidos durante al menos 5 años. Conclusiones: Las estrategias de diagnóstico y tratamiento del retinoblastoma necesitan ser actualizadas. Para ello, una buena coordinación entre pediatras y oftalmólogos es esencial. El manejo en centros de referencia, que dispongan de la tecnología y experiencia necesarias, debería contribuir a aumentar la tasa de preservación de órganos

OBJETIVOS: The number of enucleations and visual sequels due to retinoblastoma is high. The aim of this study was to evaluate the different diagnostic aspects and propose strategies that might improve the clinical management of this condition. Method: A retrospective study was conducted on 38 patients with retinoblastoma studied genetically (29 unilateral, 9 bilateral). The evaluation included: age of onset, clinical signs, and time since onset, number of enucleations, time to diagnosis, and survival at 5 years. Results: Leukocoria was the main clinical sign (present in 90% of cases). The mean diagnostic delay was 3.2 months. Among the unilateral cases, the eyes were enucleated in 76%, and 55% in the bilateral forms. Only one death was found among the 25 patients followed-up for at least 5 years. Conclusions: Retinoblastoma diagnostic and treatment strategies need to be updated. Good coordination between paediatricians and ophthalmologists is essential for this. Its management in reference centres, which have the necessary technology and experience, should contribute to increase the rate of organ preservation

Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex.

Major depression might originate from both environmental and genetic risk factors. The environmental chronic mild stress (CMS) model mimics some environmental factors contributing to human depression and induces anhedonia and helplessness. Mice heterozygous for the synaptic vesicle protein (SVP) vesicular glutamate transporter 1 (VGLUT1) have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour. Here, we aimed to identify, in these two experimental models, gene expression changes in the frontal cortex, common to stress and impaired glutamate function. Both VGLUT1(+/-) and CMS mice showed helpless and anhedonic-like behavior. Microarray studies in VGLUT1(+/-) mice revealed regulation of genes involved in apoptosis, neurogenesis, synaptic transmission, protein metabolic process or learning and memory. In addition, RT-PCR studies confirmed gene expression changes in several glutamate, GABA, dopamine and serotonin neurotransmitter receptors. On the other hand, CMS affected the regulation of 147 transcripts, some of them involved in response to stress and oxidoreductase activity. Interestingly, 52 genes were similarly regulated in both models. Specifically, a dowregulation in genes that promote cell proliferation (Anapc7), cell growth (CsnK1g1), cell survival (Hdac3), and inhibition of apoptosis (Dido1) was observed. Genes linked to cytoskeleton (Hspg2, Invs), psychiatric disorders (Grin1, MapK12) or an antioxidant enzyme (Gpx2) were also downregulated. Moreover, genes that inhibit the MAPK pathways (Dusp14), stimulate oxidative metabolism (Eif4a2) and enhance glutamate transmission (Rab8b) were upregulated. We suggest that these genes could form part of the altered "molecular context" underlying depressive-like behaviour in animal models. The clinical relevance of these findings is discussed.