Purinergic Signaling Involved in the Volume Regulation of Glial Cells in the Rat Retina: Alteration in Experimental Diabetes

  • Andreas BringmannEmail author
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


Impairment of the glial fluid clearance from the retinal tissue is an essential step in the formation of retinal edema in diabetics. Glial fluid clearance is thought to be mainly mediated by a transcellular water and ion transport facilitated by potassium (Kir4.1) channels and aquaporins. Retinal glial cells of diabetic rats display a functional inactivation and dislocation of Kir4.1 channels which is associated with cytotoxic edema (cellular swelling) under hypoosmotic conditions. Retinal glial cells possess an intrinsic purinergic signaling cascade that prevents hypoosmotic swelling. This cascade is initiated by glutamate, and involves the consecutive activation of P2Y1 and adenosine A1 receptors, the action of the nucleoside triphosphate diphosphohydrolase-2 (NTPDase2), and a nucleoside transporter-mediated increase in extracellular adenosine. The most downstream event of the cascade, activation of A1 receptors by adenosine, results in opening of potassium and chloride channels; ion efflux equalizes the osmotic gradient across the glial membrane. Glial cells of control rat retinas express NTPDase2 and ecto-5′-nucleotidase. Diabetic retinopathy is characterized by an upregulation of glial NTPDase1. Thus, the increase in extracellular adenosine occurs mainly by a transporter-mediated mechanism in control retinas, and by both nucleoside transporters and extracellular degradation of ATP in diabetic retinas. This may result in an increased extracellular availability of the glio- and neuroprotectant adenosine in the diabetic retina. Opening of ion channels upon A1 receptor activation inhibits cytotoxic glial edema and may restore the glial capacity of fluid clearance from the edematous tissue.


Cytotoxic edema Diabetes Glial cell Purinergic receptor Rat Retina 



Adenosine 5′-diphosphate


Adenosine 5′-monophosphate


Adenosine 5′-triphosphate


Inwardly rectifying potassium


Nucleoside triphosphate diphosphohydrolase


Ionotropic purinergic receptor


Metabotropic purinergic receptor


Vascular endothelial growth factor



This work was supported by grants from the Deutsche Forschungsgemein­schaft (FOR/748, GRK 1097/1).


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Ophthalmology and Eye HospitalUniversity of LeipzigLeipzigGermany

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