Physiological signaling within and between regions of the central nervous system (CNS) involves complex interplay between neurons and vascular elements via intermediary glial cells that bridge the two. Diseases that cause neurodegeneration dysfunction or failure in this interplay or 'neurovascular coupling' creates an imbalance between the metabolic needs struggling neuronal tissue with available bio-energetic resources. Similarly, dysfunctional neurovascular coupling is implicated in degeneration of retinal ganglion cells (RGCs) and their axons in glaucoma, involving reduced capillary blood flow spanning optic nerve to retina. Vascular pericytes are specialized cells that distribute intermittently along the walls of capillaries and contribute to formation of blood vessels and maintenance of the blood-brain barrier which regulates the privileged immunity of the CNS. At the level of microcirculation in the retina, pericytes help regulate neurovascular coupling through tunneling nanotubes that help connect local networks of pericytes. The important paper by Adriana Di Polo and her colleagues (Alarcon-Martinez et al., 2022) investigates with unprecedented resolution the mechanisms through which vascular pericytes influence retinal capillaries. Using an innovative combination of transgenics and two-photon laser scanning microscopy (TPLSM) to visualize capillary pericytes in vivo, the team demonstrated that experimental glaucoma constricts capillaries through calcium-dependent mechanisms that restricts ganglion cell blood supply.
The team demonstrated that experimental glaucoma constricts capillaries through calcium-dependent mechanisms that restricts ganglion cell blood supply
That restoring calcium homeostasis in retinal pericytes restores both vascular and neuronal function while protecting ganglion cells highlights the potential utility of modulating pericyte physiology as a therapeutic intervention more generally in CNS degenerative disease.