Mechanisms underlying glial polarization in retina and brain

Glial cells, astrocytes and Müller glia, are involved in homeostatic functions in the CNS. Emanating from these cells are fine processes that interact with vasculature to form ‘glio-vascular’ interface. At this interface, the fine processes enwrap the vasculature and are called endfeet. At this site, K+ channel Kir4.1 and water channel aquaporin-4 (AQP4) are highly expressed in a polarized manner and are involved in buffering K+ and water, respectively. In several pathologies, this polarized distribution is lost suggesting an underlying mechanism that influence the polarity. In this thesis, Shreyas has explored the molecular mechanisms that are responsible for Kir4.1 and AQP4 polarity by use of novel transgenic mouse model. Evidence is provided that β1-syntrophin is involved in tethering Kir4.1 to the endfeet and that both α1- and β1-syntrophin are involved in polarized distribution of AQP4 in retina. Interestingly, β1-syntrophin plays no role in polarized distribution of AQP4 in the brain. These novel insights help us understand the basic physiology and provide future directions in search of causes and potential treatment strategies for diseases affecting the retina and brain