Glaucoma is a leading cause of irreversible blindness world-wide. The disorder is characterized by pathology of the optic nerve. The neurons of the optic nerve degenerate and no longer send the visual information from the eye to the brain. Current treatments aim to reduce the pressure in the eye, since high intraocular pressure is an important risk factor. Yet, this often does not stop glaucoma progression. Glaucoma causes blindness in 7 million people worldwide. At end of life, 10% of glaucoma patients are blind, also in the Netherlands.
Our research aims to find new treatments. We focus on the specialized retinal neurons, whose axons form the optic nerve: the retinal ganglion cells. We aim to find ways (drugs or dietary supplements) to prevent their death in glaucoma. It is not known exactly why and how these are lost. Many risk factors have been identified, including increased eye pressure, age and hereditary predisposition. Variations in more than 150 genes influence the risk for glaucoma. This suggests that the disease is heterogeneous and that it is unlikely to find one treatment that is effective in all patients. Rather we need to study each patient individually to determine his or her specific glaucoma type and select the appropriate treatment. This requires an integration of patient examination, research, diagnosis and treatment (see Figure).
As a first step towards the precision medicine for glaucoma, we founded the Eye Tissue Bank Maastricht. Upon informed consent of the patient, we collect and store the clinical data, blood (cells) and tissue. Using these data and biomaterial, we carry out research projects (see below) which should bring about this glaucoma precision medicine in the near future.
Project: Glaucoma biomarkers in Aqueous Humor and Blood
PhD student: Wouter H.J. Hubens
Aim: To identify glaucoma biomarkers which may enable more timely diagnosis and may improve our understanding of the pathophysiology.
This project is based on the use of the data and biomaterial collected in the Eye Tissue Bank Maastricht. Analysis of clinical data, images, as well as biomaterial, including DNA, holds a promise for discovery of useful biomarkers. In this PhD research, Wouter Hubens focuses on biochemical biomarkers in blood and aqueous humor.
Project: Under pressure
PhD student: Pascal A.M.M. Vroemen
Aim: to study the effects of high intraocular pressure on retinal ganglion cells
In collaboration with the Institute for Technology-Inspired Regenerative Medicine (MERLN, prof. dr. Lorenzo Moroni)
High intraocular pressure is an important risk factor of glaucoma. We aim to unravel the mechanism by which this risk factor causes glaucoma. To study this, we mimic the effects of high intra ocular pressure on retinal ganglion cells in vitro. We have made two devices: one, applying pressure to cells in culture, and the other, applying both pressure and stretch, which more closely mimics the circumstances that occur in the eye when pressure is raised. These in vitro models will also be used to test and select drugs that offer protection against the mechanical stress.
Project: Towards treatment of glaucoma by a diet that bolsters mitochondrial function
PhD student: Toni Vallbona Garcia
Aim: to study the role of mitochondrial dysfunction in glaucoma
In collaboration with dr. Florence van Tienen, prof dr. Bert Smeets, Toxicogenomics, UM Maastricht
Mitochondrial dysfunction may play an important role in the pathophysiology (of some types of) glaucoma. In this project, we aim to identify biomarkers that can identify those glaucoma patients who have mitochondrial dysfunction. Next, we will analyse the mitochondrial defect using patient cells in vitro and test whether drugs or dietary supplements can improve mitochondrial function and reduce glaucoma progression.
PhD student: Wenting You
Aim: To explore the possibility to rescue and revive dying retinal ganglion cells
In collaboration with prof. dr. Chris Reutelingsperger, Biochemistry, University Maastricht and dr. Tos Berendschot, University Eye Clinic Maastricht.
Wenting You studies the mechanism by which neuronal cells die. She studies this in single cells by live cell microscopy aiming to find ways to stop and reverse the cell death process.
Project: Generation of retinal organoids and human retinal ganglion cells
Research technician: Iris Boesten
Aim: to differentiate induced pluripotent stem cells from patients into retinal organoids and retinal ganglion cells for in vitro glaucoma disease modeling
In collaboration with dr. Florence van Tienen, prof. dr. Bert Smeets, Toxicogenomics, UM Maastricht
The best cells to use in in vitro glaucoma disease models are the retinal ganglion cells from the patients themselves. To make patient-derived retinal ganglion cells, we turn blood cells into induced pluripotent stem cells and then stimulate these cells to develop into three-dimensional tissue cultures which resemble the retina. We recently succeeded in generating these retinal organoids which contain retinal ganglion cells. Efforts are now directed towards further maturation and isolation of the retinal ganglion cells. As soon as well-differentiated retinal ganglion cells are available, we will use them in our in vitro glaucoma models in the other research projects.