Testing the Roles of Proteins in Eye Disease
At UC Santa Barbara I gained independence as a researcher. I continued my interest in neuroscience and disease by entering the lab of Dennis Clegg as a freshman. While working with Dr. Clegg I applied for and won undergraduate research grants. I learned to look at my own work critically and developed a protocol in the lab with the assistance of a collaborator.
Schematic of the eye from Webvision. Light enters through the pupil and falls on the retina. The retina is complex neural tissue with many layers.
Image adapted from Hikita et al. Link to the paper here. You are looking at the layers of the retina. It's oriented so the top layer is the layer where light hits first. Both panels are images of retinas from mouse eyes where uveitis was artificially induced. The left panel shows a retina from a mouse that has Osteopontin and the right panel is from a mouse that is missing Osteopontin. The mouse with Osteopontin has more folds in the bottom layer. The bright specks above the top layer are immune cells. The mouse with Osteopontin has more immune cells invading the space above the retina. Both the folds and the immune cells represent disease progression. This helped show that loss of Osteopontin actually lessened the progress of the experiemental uveitis.
We used eye to study neuroscience and disease. In order to read the words on this page specialized neurons in your eye react to light. The signal is transmitted through a complex hierarchy that is organized in many layers. There is a class of inflammatory diseases where the immune system incorrectly attacks the layers in our eye. This leads to the tissue in the eye being irreversibly destroyed. I worked with Sherry Hikata to study a model of inflammatory eye disease in mice. These inflammatory eyes diseases are called uveitis, and they cause 10-15% of visual impairment cases in the U.S. We found that the loss of a protein called Osteopontin led to fewer immune cells invading the eye tissue and slowed the progress of disease.
Later I worked with Erin Dunkle to research a protein with a link to Age-Related Macular Degeneration, the leading cause of blindness in the western world. The protein we were interested in, fibulin 5, is found in the spaces between cells and is part of the environment that allows cells to function. Genetic studies showed that there were seven mutations in this protein that were associated with the disease. I wrote a proposal to study if these mutations affected fibulin 5’s ability to interact other proteins. We hoped that if we could understand how the mutations affected fibulin 5’s function that we could better understand the cause of Age-Related Macular Degeneration.
I spent increasing amounts of time in lab in the year I researched Age-Related Macular Degeneration. I found that I enjoyed reading technical papers and troubleshooting. There was a lot of troubleshooting because I was working with other researchers to set up a new protocol in our lab. My classes started to feel like they were distracting me from my science. Even though I graduated before I could see the project to the end, it was the ownership I felt over my research that led me to apply for graduate school the following fall.