Neuro-vascular coupling retina

It is well known that in the human retina blood flow and neural activity are tightly coupled. This coupling between neural activity and blood flow - also known as neurovascular coupling - is one of the physiological key features that allows neural tissues such as the retina or the brain to adapt their perfusion to changes in local metabolic demands. Because of its easy accessibility, the eye offers the unique opportunity to directly visualize the microvasculature and poses therefore a promising target for the investigation of neurovascular coupling by simple visual stimulation. Further, it has been shown that a break-down of neuro-vascular coupling is an early event in neurodegenerative disorders of the eye such as glaucoma. As the neuro-retina shares considerable structural and functional similarities with the brain the eye may also be a promising approach to study disease of the central nervous system. As such, it has been shown that changes in neural tissue of the brain as they occur for example in Alzheimers disease (AD) are also reflected also in anatomical changes of the neuro-retinal tissue. However, whether this holds true also for functional changes as neuro- vascular coupling is currently unclear. The project described in this grant proposal seeks to test the hypothesis that retinal neuro- vascular coupling is impaired in patients with AD or mild cognitive impairment. Further, ocular blood flow and retinal oxygenation in patients with AD will be characterized. This will increase our knowledge on neuro-vascular coupling and may lead to a better understanding of the pathophysiology of neurodegenerative disease. Further, using the eye as an opportunity to visualize neuronal dysfunction, this may in future offer a new and promising method for the early identification of risk patients.

Alzheimer's disease is the most common cause of dementia, associated with memory loss and a decline in other cognitive abilities. However, the early diagnosis and identification of high-risk persons is challenging. Recent evidence indicates that patients with Alzheimers disease show also functional and anatomical changes on the level of the retina. As the retina allows to non-invasively investigate the microcirculation in a neural tissue, the current project was designed to investigate whether ocular blood flow regulation and oxygen metabolism of the retina is altered in patients with Alzheimers disease. Interestingly, our data show that in patients with Alzheimers disease and patients with mild cognitive impairment retinal blood flow is reduced. Further, this reduction is accompanied by an altered oxygen metabolism and a thinning of neural retina. Thus, our data strengthens the hypothesis that functional alterations of the brain are reflected in the human retina. Therefore, functional alteration of the retina may in future serve as a surrogate parameter for the early diagnosis and follow up of neurodegenerative diseases.