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| Cláudia Cavadas |
| Group Leader |
Assistant Professor
Faculty of Pharmacy
University of Coimbra |
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+351 963928766 |
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| Group Research Goals |
The retina is a neuronal structure highly susceptible to several insults, such as hyperglycemia, excitotoxicity, inflammation and exposure to drugs. Our group is actively committed to identify important players and mechanisms mediating retinal and neuronal damage, with the main goal of devising new therapeutic targets and strategies to treat retinal or brain degenerative diseases.
We will clarify the role(s) of neuropeptide Y (NPY) in retinal physiology, and further investigate the potential neuroprotective and regulatory effects of NPY on retinal progenitor cell proliferation and differentiation.
We will continue to study the impact of hyperglycemia in the retina, namely on exocytosis events, on the molecular mechanisms underlying changes in AMPA receptor subunits expression in retinal cells, and on the regulation of retinal microglia.
The evaluation of the potential harmful effect of ecstasy in rat retinal physiology and morphology is another goal of our group.
The identification of the signaling pathways and molecular mechanisms responsible for the proliferative/antiproliferative effects of nitric oxide on neural stem cells is another main research interest of our group.
In a project of close cooperation with the pharmaceutical industry, we are evaluating the neurotoxicity/safety profile of eslicarbazepine acetate (developed by BIAL, Portugal) and its metabolites, as compared to other antiepileptic drugs. We are also investigating the effects of these drugs on the proliferation and fate of neural stem cells.
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| Figure Legend – NPY increases the proliferation of retinal neural progenitor cells. rat retinal neurons in culture (A,B) were exposed to NPY (100 nM), for 48h (B), and were immunostained for nestin (green) and BrdU (red). Retinal neural progenitor cells in proliferation (yellow) in control (A) and in NPY - treated cultures (B) indicated by arrows. Scale bar: 50 µm. |
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| Other Research Interests |
| Besides the major line of research in the laboratory, we are also studying the crosstalk between adrenal chromaffin cells and adipocytes, and the role of NPY and its cleavage products on adipose tissue physiology. |
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| Main Achievements |
Starting by the hypothesis that glutamate, the main excitatory neurotransmitter in the retina, might be involved in the pathogenesis of diabetic retinopathy, we found that diabetes or elevated glucose levels can impair the uptake and the release of excitatory neurotransmitters in the retina and alter the expression of ionotropic glutamate receptor subunits. In fact, we observed that diabetes changes the expression of ionotropic glutamate receptor subunits in the human retina, suggesting that glutamatergic transmission in the retina might be compromised early in the course of diabetes. Moreover, inflammation, and activation of microglial cells, has been shown to have an important role in diabetic retinopathy. We have shown that high glucose alters the purinergic signaling system in the retina, resulting high levels of extracellular ATP that may lead to inflammation involved in the pathogenesis of diabetic retinopathy. Moreover, we observed that Muller cells do not influence the adhesion of leukocytes to retinal endothelial cells.
We have also described that ecstasy (MDMA) induces retinal cell death, and we identified neuropeptide Y (NPY) as neuroprotective agent against this insult. Moreover, NPY stimulates the proliferation of retinal progenitor cells mediated by the activation of NPY Y1, Y2, and Y5 receptors as well as the by the nitric oxide (NO)-guanylyl cyclase pathway. This pathway is also activated by NPY when it stimulates catecholamine release from mouse neuronal-like cells (chromaffin cells).
The study on proliferation of endogenous neural progenitor cells, as a strategy to promote neuronal repair, showed that NO stimulates the proliferation of neural stem cells by passing the epidermal growth factor receptor.
Moreover, in a parallel research line, our results show that eslicarbazepine acetate (BIA 2-093) and its metabolites are not toxic to hippocampal neurons compared to carbamazepine or oxcarbazepine.
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| Group members |
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| Raquel Santiago |
| Ph.D. Student |
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| Ana Rita Álvaro |
| Ph.D. Student |
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| Célia Aveleira |
| Ph.D. Student |
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| Bruno Carreira |
| Ph.D. Student |
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| Gabriel Costa |
| Ph.D. Student |
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| Joana Gaspar |
| Ph.D. Student |
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| Áurea Castilho |
| Ph.D. Student |
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| João Martins |
| M.Sc. Student |
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| Filipa Baptista |
| B.Sc., PhD. Student |
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| Maria Inês Morte |
| B.Sc., PhD. Student |
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| João Martins |
| B.Sc., M.Sc. Student |
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| Joana Liberal |
| B.Sc., M.Sc. Student |
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| Further Information and Publications |
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