Helmut Ecker Endowed Chair Professorship - Molecular mechanisms driving age-related macular degeneration (AMD)

Main Research Themes of the Clark Lab

Work in the AG Clark lab centres around understanding how a complex multicellular tissue such as the human retina can maintain such resilience, longevity, and immune homeostasis. Understanding this allows us to better understand when these go wrong in diseases such as age-related macular degeneration (AMD).

Age-related Macular Degeneration (AMD)
is the third leading cause of irreversible blindness in the world, affecting millions of people around the globe. The disease manifests itself by the progressive destruction of the macula, the central part of the retina, which leads to the loss of central vision. Although a multifactorial disease, AMD is predominantly genetically driven. However, the biochemical consequences of these genetic risk variants are not entirely understood. The Clark lab’s use of human donor eye tissues and patient blood samples has allowed them to make the link between genetic susceptibility and molecular mechanisms that drive the disease.

The role of the retinal pigment epithelium (RPE) cells in maintaining photoreceptor stability and function is well regarded and accepted. However, what it less appreciated is the role of the RPE cells underlying extracellular matrix (ECM), termed Bruch’s membrane, on their function and ability to support the neuroretina. Recent discovers make clear the fundamental importance of correct Bruch’s membrane structure and composition in maintaining a healthy environment in the back of the eye. The Clark lab is particularly interested in understanding the interactions between RPE cells and Bruch’s membrane, how this alters RPE cell gene transcription, protein expression and responses to stressors such as high metabolic turnover and oxidative stress.

The complement system represents a very powerful part of the innate immune system. Primarily responsible for protecting a host from bacterial infection, it also plays a significant role in the co-ordination between innate and adaptive immunity. A number of conditions are associated with a dysfunctional complement system that affect the brain, kidneys, and eyes as well as systemic disease. The Clark lab, through their work in ocular disease, continues to have an interest in controlling aberrant complement activity as a means to develop novel therapeutic options for treating complement-mediated disease.