Pericytes in Retinal IschemiaIschemia

Recent research has disclosed involvement of pericytes in neurovascular coupling of retinal capillaries independent of the arteriole-mediated functional hyperemia. This view is supported by studies showing expression of the contractile protein α-smooth muscle actin in capillary pericytes in low but sufficient quantities to control capillary diameter. During retinal ischemia, injured pericytes persistently contract and disrupt microcirculation as well as impairing blood-retinal barrier function. Studies revealing the link between retinal ischemia and pericyte dysfunction are reviewed in this chapter. Journals and databases (Pubmed and Google Scholar) were surveyed with the keywords “RetinaRetina”, “PericytePericytes” “MicrocirculationMicrocirculation” “CapillaryCapillaries” and “IschemiaIschemia”. Related works were reviewed. During retinal ischemiaIschemia, focal microvascular constrictions emerge at pericytePericytes locations, suggesting that contracted pericytesPericytes constrict the capillariesCapillaries and disrupt microcirculationMicrocirculation as previously reported in cerebral and cardiac ischemiaIschemia. In addition to ex vivo studies, the colocalization of capillaryCapillaries constrictions with pericytesPericytes was also observed in vivo in retinasRetina of NG2-DsRed transgenic mice. PericytePericytescontractionsContraction persisted after recanalisation, causing incomplete reperfusionReperfusion of the retina. Studies with calcium-sensitive fluoroprobe Fluo-4 and genetically-encoded calcium indicator, GCaMP6, showed that a sustained intrapericytic calcium elevation mediated persistent constrictions. Calcium increase and constrictions were coincident with loss of peri-microvascular glycogen, suggesting that glycogen can support microvascular calcium homeostasis within the first hour of ischemiaIschemia by providing glucose. Indeed, inhibition of glycogen utilization accelerated the emergence of ischemic microvascular constrictions. Intravitreal injection of adenosine reversed capillaryCapillaries constrictions possibly by relaxing pericytesPericytes, encouraging that incomplete reperfusionReperfusion can be reverted. Ischemic pericytePericytes injuryInjuries also contributes to increased blood-retina barrier permeability and causes delayed pericytePericytes loss and angiogenesisAngiogenesis, which have been extensively characterized in diabetic retinopathyDiabetic Retinopathy. Recent research has documented the crucial role of pericytesPericytes in retinal ischemiaIschemia. Studies showing reversal of these pathological events create exciting opportunities for treatment of retinal diseases of ischemic origin.