Characterization and modulation of the Renin-Angiotensin System in Diabetic Retinopathy

Diabetes mellitus is a chronic disease whose numbers of affected individuals are substantially increasing. Diabetes-associated complications include Diabetic Retinopathy (DR), the main cause of visual impairment and blindness. DR is a progressive pathology affecting the retina, caused by chronic hyperglycaemia. From the several associated risk factors, hypertension has been considered a key player in DR. Renin-Angiotensin System (RAS) is the hormonal cascade responsible for the control of blood pressure. This system can be divided in two main axes: a deleterious one that promotes vasoconstriction, inflammation, angiogenesis and increased oxidative stress and a parallel axis known to counterbalance these effects. Both axes’ components have been identified in the eye and we have shown that the prejudicial axis is modulated by glucose. In this work we aimed to characterize the expression of the RAS protective axis in retinal pigment epithelium (RPE) cells and evaluate the effects of its modulation by glucose and direct renin inhibition. The expression of Angiotensin-converting enzyme 2, Angiotensin (1-7) and Mas1 were detected in RPE cells. A decrease in the expression of these components was observed in high glucose conditions, showing a RAS imbalance. These results are supported by the results obtained in the retina of a type 1 diabetic animal, the Ins2Akita mouse. RAS dysregulation triggers DR hallmarks such as oxidative stress and angiogenesis. Thus, RAS blockade can affect DR development and progression. When simulating RAS overactivation, expression of the protective components increased over time, pointing to an initial protective role that needs further investigation. When treating cells with a renin-blocker, aliskiren, decreased levels of Angiotensin-converting enzyme 2 and Mas1 were observed, probably caused by the non-formation of angiotensin peptides. Overall our results are indicative of an early effect of the protective arm of RAS in the glucose-induced RAS dysregulation

Genetic and Epigenetic Regulation of <i>Drosophila</i> Oocyte Determination

Primary oocyte determination occurs in many organisms within a germ line cyst, a multicellular structure composed of interconnected germ cells. However, the structure of the cyst is itself highly diverse, which raises intriguing questions about the benefits of this stereotypical multicellular environment for female gametogenesis. Drosophila melanogaster is a well-studied model for female gametogenesis, and numerous genes and pathways critical for the determination and differentiation of a viable female gamete have been identified. This review provides an up-to-date overview of Drosophila oocyte determination, with a particular emphasis on the mechanisms that regulate germ line gene expression