UC San Diego

The network of blood vessels in the central nervous system is critically important for nutrient delivery and waste removal in higher organisms. A special set of properties distinguishes blood vessels in the central nervous system from those in other organs, because these vessels must provide an extra layer of protection and responsiveness to the real-time demands of neurons. Much is known about way the normal physiology of neurons induces changes in local blood vessels to re-direct nutrient flow and relieve the buildup of waste products. However, there are many potential interactions between neurons and blood vessels about which we know very little. Whether vessels respond to different types of neuronal dysfunction, and if neural activity plays an important role in development of the vascular network are two such unexplored questions. This dissertation is comprised of several projects which all address the underlying mechanisms, consequences, and applications of, neural-vascular interactions in retinal development and disease.

The aim of the first study (Chapter 2) was to determine whether early spontaneous neural activity is the postnatal mouse retina is related to contemporaneous angiogenesis. We found that activity of the cholinergic retinal circuitry was necessary to establish proper layer-specific vascular development and to turn on blood-retinal barrier properties, and elucidated the signaling pathways involved in this process.

The aim of the second study (Chapter 3) was to determine whether specific injury to neurons in the retina would alter transcription in endothelial and microglial cells. We found a number of transcriptomic changes in these cells that may represent RNA originating from non-microvascular cells.

These studies describe new findings concerning the basis for intercellular communication between neurons and blood vessels in the retina, both during development and disease. A better understanding of neurovascular interactions may promote novel therapeutic strategies and biomarker discovery for blinding diseases of development and aging.