Translational Eye Research
Glaucoma is a progressive sight-threatening neurodegenerative disease and the most common cause of irreversible blindness that typically remains silent until very severe. Glaucoma is defined as a progressive optic neuropathy characterized by the loss of the retinal optic nerve cells (the retinal ganglion cells (RGCs)). RGCs transfer nervous signals from the retina to the visual centers in the brain through the optic nerve.
Hence, glaucomatous degeneration affects image perception leading to defects in the visual field and eventual blindness. The major risk factors for developing glaucoma are, in addition to age, elevated intraocular pressure (IOP) and family history. In this context, IOP is the only current treatable risk factor to slow the rate of glaucomatous neurodegeneration. Yet, one third of glaucoma patients present a normal IOP. Thus, focus has shifted to other concomitant risks factors involved in glaucomatous degeneration such as excitotoxicity -regulated in part by Müller glia-, altered blood flow, mitochondrial dysfunction, oxidative stress, and inflammation.
1. In vitro and ex vivo studies to understand the pathophysiology of glaucoma – focus on RGCs and Müller glia, the main partners of RGCs in the retina. Research techniques: recruitment and generation of patient cohorts, skin biopsies, culture of human fibroblasts and human induced pluripotent stem cells (hiPSCs), primary cell cultures and eye explants of murine animal models of glaucoma, metabolic studies (i.e. Seahorse analysis), GC-MS, transcriptomics, metabolomics, viability assays, Western blot, immunohystochemistry.
2. In vitro studies to investigate the efficacy and side effects of current treatments strategies in glaucoma – focus on the mucin producing conjunctival cells, the globet cells. Research techniques: culture of human globet cells from eye donors, viability assays, proteomics.
3. Human studies to determine the role of vascular function and energy metabolism in patients with glaucoma – generation of metabolic stress and search for biomarkers in glaucoma. Research tecniques: recruitment and generation of patient cohorts, model to induce systemic hypoxia in glaucoma patients and controls, blood sampling, ELISA, leucocyte isolation, Western blot, metabolic analysis (i.e. Seahorse analysis).
4. Clinical and epidemiological studies to improve the management of glaucoma – a search for improved screening methods to detect glaucoma. Research techniques: use of databases at The National Registry, The Drug Registry, Patients with glaucoma, multicenter studies, and novel tools to detect unrecognized visual field defects.
5. Ex vivo studies in animal models of Alzheimer’s disease to investigate neurodegenerative processes in the retina linked to the disease progression. Research techniques: eye explants of murine animal models of Alzheimer disease, GC-MS, viability assays, Western blot, and immunohistochemistry.