Sónia Simão, CBMR researcher, won an honorable mention at “Prémio Janssen Inovação 2016” with the project “Aliskiren as a new therapeutic approach for the treatment of diabetic retinopathy”. The project, developed with Daniela F. Santos and Gabriela A. Silva, aims to investigate the RAS (The renin-angiotensin system) in diabetic conditions and test the effectiveness of Aliskiren, as a drug with potential to be used in the design of new approaches for the treatment of diabetic retinopathy.
More about the project: Unhealthy lifestyles and an aging population significantly contribute to the high incidence of diabetes worldwide. This metabolic disease culminates in threatening complications such as diabetic retinopathy (DR). This visual disorder is the main cause of acquired blindness among working age adults. An effective therapy for DR has not been established so far; current therapies halt but do not revert the disease and encompass some adverse side effects. Therefore, further research is needed to better understand the disease and define new therapeutic targets.
The renin-angiotensin system (RAS) has been identified in the eye and might contribute to ocular damage. The present study was designed to investigate the RAS in diabetic conditions. For this we will focus on the retinal pigment epithelium (RPE), a retinal cell type responsible for maintaining the integrity of the retina and known to be deeply compromised in DR.
The direct renin inhibitors are a new generation of RAS inhibitors and aliskiren is the only in this class approved for medical use. Based on its action, the present study tested the efficacy of this drug in decreasing downstream events derived from RAS activation such as oxidative stress and angiogenesis.
We observed that RPE cells express the main components of the RAS and this system was significantly deregulated by hyperglycemia. Exposure of RPE cells to aliskiren inhibited the activity of renin and consequently decreased the levels of angiotensin II. Aliskiren also reduced the translocation of the (pro)renin receptor to the cellular membrane of RPE cells preventing the activation of ERK1/2. Furthermore, RAS activation induced oxidative stress and angiogenesis in RPE cells, which were effectively prevented by aliskiren.
In conclusion, our findings demonstrate that aliskiren successfully inhibit the RAS in RPE cells. We described in detail the mode of action of aliskiren in the RPE cells and found this drug to have antioxidant and anti-angiogenic properties. These new features of aliskiren suggest that this drug has potential to be used in the design of new approaches for the treatment of diabetic retinopathy.