Research

Background

Our research is dedicated to pathologic processes within the eye. We are focused on an eye disease, which is one of the leading causes of blindness in the world, the Primary Open Angle Glaucoma (POAG). POAG affects at the moment around 3 million people worldwide, and the numbers are rising with the increasing life expectancy in the world.

POAG is defined as an optic neuropathy. In patients with POAG, the optic nerve head (ONH) shows characteristic cupping correlated with visual field defects. The progressive optic neuropathy is characterized by irreversible loss of retinal ganglion cells (RGC). The critical risk factor for axonal damage at the ONH is an elevated intraocular pressure (IOP). The elevated IOP in POAG patients is due to an increased resistance against aqueous humor outflow in the outflow tissues, trabecular meshwork and Schlemm ‘s canal.

The increase in IOP correlates with axonal loss in the ONH. Damage to the optic nerve is occurs in the lamina cribrosa (LC) region of the ONH, which is composed of characteristic sieve-like connective tissue cribriform plates through which RGC axons exit the eye.

Research

Research at our laboratory focuses on the discovery of molecular pathways involved in the pathological processes of glaucoma. The molecular characterization of homeostatic systems in the outflow tissues and in the optic nerve of mammalian eyes is critically required to preserve the visual function.

Our laboratory utilizes a broad spectrum of techniques to analyze the pathological processes within the eye, from the classical histology and electron microscopy, molecular biology techniques.? We are using molecular, cellular, in situ and animal model systems to analyze the molecular causes for the onset and progression of POAG.

Our research is funded by the German Research Council and by the BrightFocus Foundation.

We have strong collaboration with numerous national and international scientific groups.

Projects

1)? Homeostatic balance of growth factors and their influence on the intraocular pressure IOP.? ?

The outflow resistance is influenced by the extracellular matrix within the trabecular meshwork and by the contractility of the trabecular meshwork cells. The production of the extracellular matrix and the contractility of the trabecular meshwork cells is modulated by the Connective Tissue Growth Factor (CTGF), a downstream mediator of transforming growth factor (TGF)-β2. We could demonstrate that overexpression of CTGF causes glaucoma within the eyes of mice and so we developed the first animal model for POAG in the world. The glaucoma model will help us to get a profound understanding of the POAG development.

2)? Therapeutic layer-by-layer coated nanoparticles: Investigation of the transport and cellular uptake in the trabecular meshwork

Topical eye drops are the first-line medication for controlling the IOP. Unfortunately, they have a long list of drawbacks, e.g. 20% of patients show poor compliance, 30 to 40% of the patients miss the eye during eye drop administration, or even worse, about 70% of patients are supposed to stop the medication after 3 years of treatment. Consequently, there is a strong need for new therapeutic concepts to prevent vision loss.

Our goal in this project is to develop new layer-by-layer coated nanoparticles that can affect specific the outflow tissues and thereby helping to reduce the increased outflow restistance.

3)? Role of Non-Coding RNAs in Outflow Resistance Dysregulation

Lowering of intraocular pressure (IOP) in glaucomatous patients may slow or stop progression of damage to their optic nerve. Some of the pathology responsible for the elevated IOP associated with glaucoma lies in the conventional aqueous humor outflow pathway, which is the eye’s main drainage system for aqueous humor, a fluid bathes the lens and circulates through other parts of the front of the eye. Somewhat remarkably, no current pharmacological therapy for glaucoma is directed at this pathway. This project focuses on genetic factors affecting that pathway, specifically, the functional role of non-coding RNAs on the nitric oxide system and their potential involvement in regulation of the conventional outflow pathway.

The investigation could lead to a new therapeutic approach that would add to current therapies and prove useful in preventing disease progression.

This research is funded by the?????

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