These presumptive Mu�� ller glia retain Notch signaling and are prevented from differentiating into bipolar neurons or rod photoreceptors; however, their glial identity is labile, and it is only with the increase in the gliogenic signals over the next week that secondary mechanisms 439083-90-6 stabilize the glial fate. The model leaves several questions. Why do non-glial postmitotic progeny, eg. rod photoreceptors, 808118-40-3 downregulate Notch signaling components, whereas the developing Mu�� ller glia retain them? What drives the expression of the receptors for the gliogenic factors as the progenitors transition to Mu�� ller glia and as the Mu�� ller glia mature? What are the mechanisms that stabilize the Mu�� ller glial fate so that Notch is no longer required after postnatal day 12? A better understanding of these mechanisms might enable reprogramming of these cells to retinal progenitors as a basis for regeneration after damage, as occurs in non-mammalian vertebrates. In situ hybridization was carried out as described in previous publications using digoxigenin-labeled probes for Hes5, Notch1, Dll1, Dll3 and Neurog2 . Eyes were fixed overnight at 4uC in modified Carnoy��s solution , 10% glacial acetic acid), embedded in paraffin and sectioned at 6�C8 mm. Slides were hybridized with probe overnight hybridization and hybridized probe was detected using anti-Digoxygenin alkaline phosphatase conjugated antibody . After in situ hybridization, sections were post-fixed in 4% PFA and rinsed in PBS prior to immunofluorescent labeling. The association between diabetes and cardiovascular disease is beyond dispute, with diabetes being an independent risk factor for the development of cardiovascular complications, accounting for 80% of deaths among diabetic patients . However the mechanisms underlying the development of chronic heart failure in diabetic patients remain uncertain. A large body of evidence demonstrates that diabetic cardiomyopathy exists, independent of hypertension and underlying coronary artery disease . DCM is characterized particularly by fibrosis and hypertrophy in the left ventricle of the heart manifested as abnormal LV diastolic function preceding LV systolic dysfunction . While the mechanisms underlying these pathological changes are not well understood, reactive oxygen species have been identified as likely mediators in the pathophysiology of diabetic cardiovascular complications .