Local and Systemic Inflammation in a Mouse Model of RPE Oxidative Damage
CollaboratorAlfred S. Lewin, PhD University of Florida
Macular degeneration is a leading cause of blindness among the older population of the USA and other developed countries. Inflammation has been linked to age-related macular degeneration (AMD). My research goal is to improve a mouse model of this disease by introducing pro-inflammatory cues, and to experiment with a method of decreasing inflammation in the eye to test the idea that localized control of inflammation could help protect vision. If successful, this method could also be tested in other diseases linked to aging and inflammation, such as Alzheimer’s disease.
The goals of this project are (i) to improve a mouse model of macular degeneration, and (ii) to test a genetically modified virus that can control inflammation within the eye of this mouse model. In the first set of experiments, we will cause a mild inflammation in this mouse model. We will inject these mice with either oxidized proteins, bacterial components, or normal saline in a single injection when they are young. These mice will then be follow using techniques employed by clinicians to evaluate how their retina degenerates as they age. Our hypothesis is that by causing a mild inflammation in these animals, we will be able to induce changes similar to those seen in patients with AMD, because these animals already have a propensity to develop a slow retinal degeneration due to increased oxidative stress in their retinas. In the second set of experiments, we will use a genetically modified virus to deliver a gene known to inhibit inflammation in the eye. We will inject our mouse model with this virus or with a similar virus delivering an irrelevant gene in the opposite eye. These mice will be follow by our group as described in the previous experiments, and we will look for effects that could indicate protection of the retina. We will also use techniques that can tell us whether any of these effects are due to the anti-inflammatory properties of our virus, or due to an unknown function. These experiments are innovative because they seek to improve a mouse model based on current knowledge from human disease, while also testing novel therapies that could be of benefit for affected individuals. Completion of this research project will improve our knowledge of how systemic inflammation could modify the progression of AMD.