Ferrington Research

Research topics:  Molecular mechanisms of aging and age-related macular degeneration; proteomics; proteasome degradation of proteins; protein oxidation; antioxidant enzymes; retinal pigment epithelial cells

 The goal of our research is to help define the cellular mechanisms involved in the retinal degeneration accompanying aging and age-related macular degeneration (AMD).  The focus is on understanding the role of protein oxidation and how defects in the proteasome, the enzyme responsible for removing oxidized proteins from the cell, impact on cell function.  We hypothesize that a loss of proteasome function and the subsequent accumulation of oxidized proteins is an integral part of the progressive loss of retinal function with aging and disease (see Figure 1). 

Figure 1  Oxidized proteins accumulate when there is increased damage by free radicals and/or proteasome function is decreased.

Our investigative approach incorporates techniques in biochemistry, molecular biology, cell biology and biophysics, using rodent models of aging, human donor eyes, genetically altered mice with reduced antioxidant enzymes, cell culture, and purified proteins.  There are currently three main projects that are investigating one or more aspects of our hypothesis. 

• First, we are using proteomic technology to identify proteins that are modified with aging and AMD.  Proteomics is a powerful analytical approach to study protein properties (i.e., expression, oxidative modifications) using a combination of two-dimensional gel electrophoresis to resolve proteins, image analysis to compare and quantify protein expression, and mass spectrometry in concert with bioinformatics to identify the altered proteins.  Identification of proteins that are altered with aging or disease will help discern cellular pathways that are susceptible to age-related changes. 
  

• In a second project, we are investigating changes in expression and function of the proteasome with oxidative stress, aging, and AMD. 
  

• A third project is focused on investigating the consequences of increased intracellular free radicals using cells cultured from mice expressing lower levels of specific antioxidant enzymes.