The eye as a window to the brain in heart failure

The eye as a window to the brain in heart failure. When the heart is injured such as after a heart attack, it may not be able to pump enough blood to meet the needs of the body. This is especially dangerous for organs like the brain that need a lot of oxygen and nutrients to function. The lack of normal blood supply leaves patients more likely to develop progressive cognitive impairment (CI) and dementia, which is hard to diagnose before it is too late. The eye is the only part of the brain visible to the outside world. Therefore, we look for linked changes in the eye and brain at three different timepoints in the case of heart failure (HF). Giving us a “window to the brain” that may help diagnose CI at an early stage before it is too late to treat. It has been reported in a mouse model of HF that cognitive impairments arise at 12 weeks into the disease. We therefore used two earlier timepoints in this model, 6 and 3 weeks to seek changes that lead to this result. These changes include memory function, the structure of neurons, and changes in the immune cells of the brain, which become activated during brain damage. We also investigate how the immune cells of the eye respond along this timeline, to look for a link to the brain and to see what changes occur first. A heart attack was induced in the mice that resulted in HF. The mice then lived with HF for 3, 6 and 12 weeks to create our disease timeline. We used behavioural testing to assess their memory function before harvesting the brains and eyes. We sectioned these organs and used markers to visualise immune cells and neurons. We could then assess changes in structure indicative of immune activation and neuronal degeneration. We discovered that memory changes only became apparent by 12 weeks although inflammation was increased in the brain and eye as soon as 6 weeks. The immune cells of the eye were observed to have changed to an inflammatory state at 6 weeks, and this persisted through to 12 weeks. This kind of sustained inflammation in the eye and brain is a hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s which progress over time and severely impact quality of life. These results point to the potential of the eye as a marker of brain health in HF and other heart diseases. Scanning methods in the eye are simple and non-invasive and may allow for the diagnosis of neurodegeneration before cognitive function has been severely impacted. Preventative treatment could then be applied, that may help HF patients live a longer and more enjoyable life for themselves and their families. Master’s Degree Project in Molecular Biology 60 credits 2020 Department of Biology, Lund University Advisor: Anja Meissner, Ulrica Englund-Johansson Vascular Biology / Ophthalmology, BMC Lund. (Less)