Student Profile: Juan Sebastian Pena

Research Summary
The incidence of progressive neovascular retinopathies (NRs) that result in permanent vision loss such as wet age-related macular degeneration, diabetic retinopathy and neovascular glaucoma, are expected to increase by roughly 33% in adults of developed nations like the United States by 2030. NRs  develop as a result of the breakdown of the inner blood retinal barrier (iBRB), a physiological barrier formed mainly by tight junctions of endothelial cells (ECs) and foot processes of glial cells. The iBRB controls the transport of molecules from the blood into the retinal parenchyma. In disease, ECs upregulate the production of vascular endothelial growth factor (VEGF), which activates Muller glia (MG) to induce reactive gliosis, a group of processes that involve changes in cellular behavior. Although initial MG gliosis is neuroprotective, the prolonged dysregulation of retinal homeostasis as a result of NRs leads to disruptive behaviors and subsequent glial scar formation. Although retinal scarring is the main outcome from retinal insults, the complex pathology of the retina is affected by a myriad of regulatory components that make it nearly impossible to identify specific, transient biochemical changes that lead to the onset of gliosis. Therefore, in vitro platforms can help to assess the individual contribution of MG to retinal scarring within controlled cellular systems. Specifically, microfluidics (μFs) are powerful platforms able to recreate geometrical and/or physiological conditions of complex organs and tissues with high accuracy. My work has focused on studying the behavior of MG within μFs to identify their intrinsic response to a particular stimulus, specifically the factors that trigger gliotic responses and how they develop over time. Furthermore, I have designed and developed a microfluidic system that enables the co-culture of ECs and MG on a porous membrane under constant perfusion, effectively forming an in vitro physiological barrier. I am interested in exploring the reactive behavior of MG and their synergistic interaction with ECs in diabetic retinopathy. Using rat diabetic cells and conditioned media within a hypoxic medium I will assess changes in permeability and integrity of the in vitro barrier, focusing on the reactive changes in MG and how they affect the functionality of the in vitro barrier overall. My contribution to science will be new insight on MG behavior, which will help to shape our understanding of retinal pathology to develop new therapeutics that aim to reduce the progression of irreversible vision loss.