Extracellular lactate as an alternative energy source for retinal bipolar cells.

Retinal bipolar and amacrine cells receive visual information from photoreceptors and participate in the first steps of image processing in the retina. Several studies have suggested the operation of aerobic glycolysis and a lactate shuttle system in the retina due to the high production of this metabolite under aerobic conditions. However, whether bipolar cells form part of this metabolic circuit remains unclear. Here, we show that the monocarboxylate transporter 2 is expressed and functional in inner retinal neurons. Additionally, we used genetically encoded FRET nanosensors to demonstrate the ability of inner retinal neurons to consume extracellular lactate as an alternative to glucose. In rod bipolar cells, lactate consumption allowed cells to maintain the homeostasis of ions and electrical responses. We also found that lactate synthesis and transporter inhibition caused functional alterations and an increased rate of cell death. Overall, our data shed light on a notable but still poorly understood aspect of retinal metabolism.

Glucagon Increases Retinal Rod Bipolar Cell Inhibition Through a D1 Dopamine Receptor-Dependent Pathway That Is Altered After Lens-Defocus Treatment in Mice.

Purpose: Members of the secretin/glucagon family have diverse roles in retinal physiological and pathological conditions. Out of them, glucagon has been associated with eye growth regulation and image defocus signaling in the eye, both processes central in myopia induction. On the other hand, dopamine is perhaps the most studied molecule in myopia and has been proposed as fundamental in myopia pathogenesis. However, glucagonergic activity in the mammalian retina and its possible link with dopaminergic signaling remain unknown. Methods: To corroborate whether glucagon and dopamine participate together in the modulation of synaptic activity in the retina, inhibitory post-synaptic currents were measured in rod bipolar cells from retinal slices of wild type and negative lens-exposed mice, using whole cell patch-clamp recordings and selective pharmacology. Results: Glucagon produced an increase of inhibitory post-synaptic current frequency in rod bipolar cells, which was also dependent on dopaminergic activity, as it was abolished by dopamine type 1 receptor antagonism and under scotopic conditions. The effect was also abolished after 3-week negative lens-exposure but could be recovered using dopamine type 1 receptor agonism. Conclusions: Altogether, these results support a possible neuromodulatory role of glucagon in the retina of mammals as part of a dopaminergic activity-dependent synaptic pathway that is affected under myopia-inducing conditions.

Malformaciones congénitas en diferentes etapas del desarrollo intrauterino / Congenital malformations at different stages in intrauterine development

Con el objeto de evaluar la participación de las malformaciones congénitas en la mobilidad del proceso gestacional se estudiaron 13,130 productos: 263 abortos espontáneos, 208 óbitos y 12,659 recién nacidos vivos. La frecuencia de malformaciones congénitas en la muestra total fué de 3.8%. En el grupo de abortos, 61.5% fueron anormales: 40.8% malformados, 30.2% anenbriónicos, 21% desorganizados y 8% molares. El 8.6% de los óbitos estaban malformados siendo en su mayoría defectos del cierre del tubo neural del tipo anencefalia. En los recién nacidos vivos el 2.5% presentaban malformaciones congénitas de las que el 1.8% eran mayores y el 0.7% menores. En el presente estudio se puede inferir por las características fenotípicas de los productos de aborto que 30% presentaban probablemente una alteración cromosómica; las malformaciones más frecuentes en este grupo fueron las faciales y los defectos de cierre del tubo neural. En los óbitos la malformación más frecuente fue la anencefalia y en los recién nacidos vivos de pié bot, los defectos de cierre del tubo neural y el labio hendido con o sin paladas hendido. Del análisis de las frecuencias encontradas en las diferentes etapas de la gestación se puede mencionar que en cada una hay una patología representativa. Se concluye que para evaluar en forma integral la influencia de las malformaciones congénitas en la morbilidad del evento reproductivo, se requiere estudiar a todos los productos de la gestación y así, establecer programas de prevención mediante asesoramiento genético