Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse

Purpose. The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. Methods. Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. Results. The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON-bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. Conclusions. Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.

Factores asociados a la predisposición a vacunarse contra la gripe pandémica A/H1N1 en población adulta del Departamento de Salud de Elche (España): influencia de las fuentes de información

Fundamento. Evaluar en población general las fuentes de información, actitudes y predisposición hacia la vacunación contra la gripe pandémica A/H1N1 de 2009. Métodos. Estudio descriptivo de carácter transversal realizado entre el 25 de noviembre y 30 de diciembre de 2009 mediante entrevista personal cara a cara a una muestra aleatoria (826) de adultos residentes en el Departamento de Salud de Elche (España). Resultados. Los encuestados manifestaron que la televisión (57%) y el médico de familia (47,9%) eran su fuente principal de información sobre vacunas. El 82,2% tenía una buena opinión sobre las vacunas, un 30,5% percibía la gripe A/H1N1 como más grave que la estacional, siendo esta percepción creciente entre los de mayor edad y con menos estudios. Un 25,4% de encuestados sentía preocupación por padecerla, sobre todo los de menor nivel educativo. Un 42,1% manifiesta su buena predisposición para vacunarse contra la gripe estacional, disminuyendo hasta un 18,4% la intención hacia la gripe A/H1N1. La predisposición hacia la vacunación crece con la edad y en el caso de la gripe A/H1N1 decrece a mayor nivel educativo. El médico de familia es la fuente de información más determinante para inmunizarse frente a gripe estacional (OR 1,43) y gripe A/H1N1 (OR 2,47). Conclusiones. Existe baja aceptabilidad de la vacuna pandémica y baja percepción de gravedad sobre la gripe A/H1N1. La experiencia previa de vacunación ante gripe estacional predispone hacia la inmunización contra gripe A/H1N1. Aunque los medios de comunicación encabezan la fuente de información más usual durante este episodio, la influencia del médico de familia en la decisión de vacunarse resulta significativa.

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.