Investigating molecular mechanisms that establish and maintain a transparent cornea in the eye

Overview

Topic status: We're looking for students to study this topic.

The cornea is a transparent, curved structure on the anterior surface of the eye. This structure admits light into the eye and helps us obtain sharply focused images on the retina. The cornea is composed of discrete layers of epithelial and connective tissue and must remain free of inappropriate structures, such as blood vessels, which may restrict the passage of light into the eye. Significant impairment of vision can occur if abnormal tissue growth occurs across the cornea. For example, in a condition pterygium a delta-shaped fibroblastic growth associated with the conjunctiva can extend across the corneal surface and significantly impair the passage of light into the eye (Figure. 1)1,2. Understanding mechanisms which establish and maintain normal cellular architecture and transparency in the cornea has the potential to generate data that will assist the development of strategies to treat or prevent debilitating ocular diseases such as pterygium. In recent years evidence has emerged that specific classes of cell membrane associated proteins, the ephrins and their associated receptors (Eph/ephrins), play key roles in the regulation of tissue morphogenesis and development in many organs. For example, there are numerous reports of the involvement of interactions between members of the Eph/ephrin family playing key roles in axon guidance, cell migration, angiogenesis and cancer3,4.

Hypothesis: Recently, we have obtained evidence in our laboratories that Eph/ephrin genes are expressed in cells of the human cornea. We therefore hypothesise that, as in other organs, interactions between the Eph/ephrins may play important roles in the establishment and maintenance of the normal cellular architecture and transparency of the cornea.

Approaches:

  1. Profiling the expression of Eph/ephrins in corneal tissues: Cells obtained from different tissue layers of the human cornea (epithelium, stroma and endothelium) will be cultured in vitro. Evidence of Eph/ephrin gene expression in cultured cells will be assessed by RT-PCR. The presence of associated proteins will also be confirmed by Western blot analysis and immunohistochemistry.
  2. Determining the functional significance of Eph/ephrin proteins in corneal tissues: In this study, the potential of Eph/ephrin proteins to influence corneal cell growth and migration in vitro will be assessed. Human corneal cells will be cultured on various biomaterials, such as fibroin6, currently under investigation for its potential use in the repair of damaged human corneas. Selected biomaterials will be coated with various members of the Eph/ephrin family and the capacity of corneal cells to infiltrate and form functional tissue layers on these structures assessed.

References:

  1. Wlodarczyk J, Whyte P, Cockrum P, Taylor H. Pterygium in Australia: a cost of illness study. Clinical & experimental ophthalmology 2001;29:370-375.
  2. John-Aryankalayil M, Dushku N, Jaworski CJ, et al. Microarray and protein analysis of human pterygium. Molecular vision 2006;12:55-64.
  3. Hirst LW. The treatment of pterygium. Survey of ophthalmology 2003;48:145-180.
  4. Lackmann M, Boyd AW. Eph, a protein family coming of age: more confusion, insight, or complexity? Science signaling 2008;1:re2.
  5. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell 2008;133:38-52.
  6. Nazarov, H.J. Jin and D.L. Kaplan, Porous 3-D scaffolds from regenerated silk fibroin, Biomacromolecules 5 (2004), pp. 718-726
Study level
Honours
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Medical Sciences

Contact
Please contact the supervisor.