Aarhus University Seal / Aarhus Universitets segl

Ebbe Toftgaard Poulsen

Research project: 

The Window of the Eye: Protein Characterization of the Human Cornea in Health and Disease

The front “window” of the eye consists of a clear structure known as the cornea (Figure 1). The cornea forms a physical barrier that protects against UV light, germs, dust, and other harmful matter that inevitably will come in contact with the eye. However, in contrast to a window, the cornea, together with the tear film, also refracts light to focus the visual input and is responsible for approximately 70% of the eye’s focusing power. Diseases or injuries that affect the shape or transparency of the cornea are thus always serious and may significantly impact vision.

Figure 1. Schematic of the human eye. The cornea is the outermost part of the eye and is responsible for focusing light via the lens to the retina in the back of the eye for subsequent transmission via the optical nerve to the visual cortex in the brain. The cornea is the also the first line of defense against e.g. UV light, germs and dust. Therefore, the cornea constitutes both an essential part of vision and a defense mechanism against harmful matter. Complications in the cornea often lead to visual impairment and thereby to reduced quality of life.

Courtesy: National Eye Institute, National Institutes of Health (NEI/NIH)

Corneal dystrophies

One particular group of corneal diseases is referred to as TGFBI-linked corneal dystrophies embracing a group of inherited eye disorders. These diseases manifest as accumulation of abnormal protein material in the cornea over time, thereby blocking ‘the window’ causing severe visual impairment (Figure 2). The process from no material to full blown visual impairment usually occurs within the first to third decades of life. The disorders affect both eyes at the same time (bilateral) and apparently do not affect other areas of the eyes or of the body in general. The current treatment of such diseases rely on laser surgery and corneal transplantation. Unfortunately, these interventions can only be performed a limited number of times before the patient is left with no further treatment option.

The abnormal accumulation of protein material occurs due to alterations (mutations) of the transforming growth factor beta-induced (TGFBI) gene. The gene encodes the protein TGFBIp that due to these alterations accumulates in the cornea. The molecular mechanisms underlying the pathobiochemistry of this process are poorly understood and are the main focus of this project. The long-term goal is to identify new therapeutic modalities for noninvasive treatment options against these devastating eye diseases.

Figure 2. Normal versus affected eye. Left: Picture of a normal human cornea. Right: Picture of protein accumulation (white matter) in the cornea in a patient suffering from Granular Corneal Dystrophy caused by a mutation in the TGFBI gene.

Corneal proteomics

The cornea is the only transparent connective tissue of the entire body, and, in contrast to other connective tissues, it has a highly ordered collagen matrix responsible for its transparent properties. We are studying the proteome of the human cornea as well as the mechanisms involved in corneal homeostasis and development of pathology. We have conducted the largest proteomic analysis of the healthy human cornea to date, looking into the different sublayers of the cornea. In addition, we have performed proteomics on common eye disorders such as Fuchs' corneal endothelial dystrophy and Keratoconus, but also on rarer conditions such as the TGFBI-linked corneal dystrophies and Meesmann dystrophy. Whenever possible, our studies involve transgenic mouse models to imitate human conditions, which would otherwise not be possible to study directly.

The research is funded by the VELUX Foundation and headed by professor Jan J. Enghild, MBG, Aarhus University.