Retinal Dysfunction & Neuroinflammation Lab

1. We demonstrated, using several in vitro and animal models, that the blockade of adenosine A2A receptors significantly inhibits retinal neuroinflammation mediated by microglial cells and confers neuroprotection to retinal cells, as for example to retinal ganglion cells. Moreover, the consumption of caffeine, an adenosine receptor antagonist, also inhibits retinal neuroinflammation and protects retinal ganglion cells (Madeira et al., 2015, 2016a, 2016b; Boia et al., 2017). [In collaboration with Vidal Sanz Lab (Univ. Murcia, Spain)]

2. In addition to adenosine A2A receptors, targeting adenosine A3 receptors with selective agonists is neuroprotective against retinal cell degeneration, and particularly for retinal ganglion cells. [In collaboration with Francesca Cordeiro Lab (UCL, London, UK)]

3. The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. We demonstrated for the first time that ascorbate uptake through SVCT2 is critical for the homeostasis of microglia and that depletion of SVCT2 triggers a proinflammatory phenotype in microglia. Moreover, we found that Src-mediated phosphorylation of caveolin-1 in microglia induces the internalization of SVCT2, and that SVCT2 overexpression or blocking SVCT2 internalization prevents the activation of microglia. [In collaboration with João Relvas Lab (i3S, Univ. Porto, Portugal)]

4. Changes in microglial cells morphology, when they become activated, are associated with the release of pro-inflammatory mediators, as well as with the activation of kinases of the Src family. We found that c-Src is necessary and sufficient for triggering microglia activation, which was accompanied by increased release of glutamate and microglia-induced neuronal loss. Inhibition of c-Src reduces retinal neuroinflammation and apoptosis. [In collaboration with João Relvas Lab (i3S, Univ. Porto, Portugal)]

5. Sitagliptin, a dipeptidyl peptidase-IV inhibitor used in the treatment of type 2 diabetes, can exert protective effects in the retina of type 1 diabetic animals by a mechanism independent of insulin secretion and glycemia normalization. Sitagliptin prevents the increase in blood-retinal barrier permeability, reduces retinal inflammation and apoptosis. These findings suggest that sitagliptin could be used to prevent or delay several pathogenic features of diabetic retinopathy, even in type 1 diabetic patients. [In collaboration with Flávio Reis Lab (iCBR, FMUC, Univ. Coimbra, Portugal)]