Contacts: stenreiro@nms.unl.pt & rita.oliveira@nms.unl.pt
Deadline for contacts: 10th March 2023
PhD Opportunity: pre-selection for FCT PhD grants application
TITLE: Gut- and Liver-Retina axis: Extracellular vesicles role in diabetic retinopathy progression
Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of visual impairment in the working-age population. The therapeutic strategies available for DR only target the later stages of the disease involving vascularization defects. However, retinal neurodegeneration and inflammation are now known to precede vascular alterations.
Recently, extracellular vesicles (EVs) became widely recognized as vehicles of systemic communication both in physiological and pathological conditions. Oliveira RM and co-workers unveiled that in a diet induced prediabetic mouse model gut EVs are spreading out diabetogenic signals in response to the local diabetogenic niche. In fact, gut EVs from prediabetic animals are proficient in inducing weight gain, hepatic lipidic accumulation and glucose intolerance, hallmarks of prediabetes, in a healthy animal, suggesting that they are key contributors for the development of diabetes and associated pathologies.
Tenreiro Lab recently generated a model of early DR in three-dimensional (3D) retinal organoids derived from human induced-pluripotent cells (iPSCs). This model has the advantage of recapitulating the cellular organization and the sensitivity to light of the human retina and importantly, it reproduces the neurodegeneration, inflammation and glial reactivity that occurs in the human retina, in early DR (de Lemos et al., submitted; submitted patent PT118368 and EU 22217331.2).
Here in propose to determine the biological role of EVs from diabetic animals on diabetic retinopathy progression. Thus, this project aims at testing whether EVs obtained from different metabolic relevant organs (liver, gut and muscle) from a prediabetic model contribute to the diabetic retinopathy early hallmarks, determining disease onset and progression. We will take advantage of our model of retinal organoids with or without early DR features.