Inflammation has been associated with the development and progression of severe retinal diseases, such as age-related macular degeneration (AMD) and retinal vein occlusion (RVO), characterized by impair vision and even blindness. According to the National Eye Institute, it is estimated that by 2040 more than 288 million people will suffer from AMD worldwide. Thus, it is of great importance to establish new pharmacological targets for the treatment of retinal disease to prevent vision loss and to improve the quality of life for affected people. The major research interests of our group focus on investigating the role of innate immune cells in retinal disease, with emphasis in resident microglia and infiltrating myeloid-derived cells as well as other inflammatory components such as cytokines and chemokines. Experimental mouse models of choroidal neovascularization, retinal vein occlusion and lipopolysaccharide (LPS)-induced retinal inflammation are employed, together with genetically modified animals, in vivo imaging techniques and molecular and cellular approaches. The goal of our research is to gain a better understanding on the role of innate immune cells in retinal disease progression and to investigate potential therapeutic targets.
Choroidal neovascularization is observed in wet AMD and it is characterized by the formation of new abnormal vessels that emerge in the choroid and grow through the disrupted Bruch’s membrane. Using an in vivo mouse model of laser-induced CNV that has been established in the lab, we have recently shown that depletion of innate immune cells by a selective colony-stimulating factor 1 receptor (CSF-1R) inhibitor, leads to faster involution of CNV in mice, suggesting a role of inflammation in the disease. Currently, we are investigating how systemic inflammation would potentially affect CNV progression and what mechanisms are involved in these actions.
LPS is an endotoxin found in the membranes of gram negative bacteria and can induce rapid inflammatory responses. We have recently established a model of systemic LPS-induced retinal inflammation, where injections of LPS for 4 consecutive days lead to breakdown of the blood retina barrier accompanied by the clustering of innate immune cells around retinal vessels, vascular dilation and leakage; and sub-retinal fluid accumulation. The model is highly reproducible and features characteristics observed in retinal diseases such as AMD and diabetic retinopathy. We have previously shown that depletion of innate immune cells with CSF-1R inhibitor totally prevents the LPS phenotype suggesting a major role of immune cells in LPS actions. Current research in the lab focuses on the investigation of LPS mechanisms of actions in the retina with emphasis on fractalkine receptor (Cx3cr1) and Toll-like receptor 4 (Tlr4) signaling in microglia and macrophages; and the contribution of endothelial cells to the inflammatory response.