ADPbetaS evokes microglia activation in the rabbit retina in vivo

To investigate whether stimulation of purinergic P2Y(1) receptors modulates the activation of microglial and Müller glial cells in the rabbit retina in vivo, adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS; 2 mM in 100 mul saline), a non-hydrolyzable ADP analogue, was intravitreadly applied into control eyes or onto retinas that were experimentally detached from the pigment epithelium. Both retinal detachment and application of ADPssS onto control retinas induced phenotype alterations of the microglial cells (decrease of soma size, retraction of cell processes) and had no influence on microglial cell density. ADPssS application onto detached retinas accelerated the process retraction and resulted in a strongly decreased density of microglial cells. The effects of ADPssS on microglia density and phenotype in detached retinas were partially reversed by co-application of the selective inhibitor of P2Y(1) receptors, MRS-2317 (3 mM in 100 mul saline). ADPssS apparently did not influence Müller cell gliosis, as determined by electrophysiological and calcium imaging records. It is concluded that rabbit retinal microglial cells express functional P2Y(1) receptors in vivo, and that activation of these receptors stimulates phenotype alterations that are characteristical for microglia activation.