Experimental Dispase-Induced Retinopathy Causes Up-Regulation of P2Y Receptor-Mediated Calcium Responses in Müller Glial Cells

Abstract

During proliferative vitreoretinopathy (PVR) Müller glial cells show an up-regulation of their responsiveness to extracellular adenosine 5′-triphosphate (ATP). In the present study, we investigated if such a glial cell response is also a feature for other retinopathies besides PVR. To this aim, the proteolytic enzyme, dispase (0.1 U), was injected into the vitreous of rabbit eyes. After 3 weeks, a distinct retinopathy had developed which showed no signs of PVR. The retinopathy was characterized by strong alterations of the retinal vasculature in the medullary rays, by photoreceptor degeneration, retinal atrophy, and activation of microglial cells. Müller cells became reactive, as indicated by up-regulation of glial fibrillary acidic protein immunoreactivity and by hypertrophy involving subretinal fibrosis. Müller cell reactivity was also evidenced electrophysiologically by a down-regulation of their inwardly rectifying potassium currents and by an up-regulation of their responsiveness to extracellular ATP. Significantly more Müller cells from dispase-treated eyes showed ATP-evoked calcium (83%) and current responses (69%) when compared with cells from control eyes (13 and 9%, respectively). The results indicate that increased responsiveness to extracellular ATP may be a more general feature of Müller cell gliosis, and is also observed in retinopathies besides PVR.

Early Glial Cell Reactivity in Experimental Retinal Detachment: Effect of Suramin

“…39 The present results indicate that, within hours of detachment, Müller cells begin to downregulate their potassium currents and to increase the responsiveness of their purinergic P2Y receptors. The data close a hitherto-existing gap in accumulating evidence 15,20,22,32,34,40,41 for the general rule that in Müller cells, the expression levels of potassium inward currents and ATP responsiveness are inversely correlated during development and retinal disease (Fig. 7).…”

Purinergic regulation of high-glucose-induced caspase-1 activation in the rat retinal Müller cell line rMC-1

“…7). Additionally, activation of P2Y receptors has been shown to regulate osmotic changes within the diseased and damaged retina and may be linked to fluxes of Ca 2ϩ or other ions that modulate caspase activity (6,14,24,48,50). However, exogenous UTP, which also triggered robust Ca 2ϩ mobilization (Fig.…”

ATP-Induced Relaxation of Porcine Retinal Arterioles Depends on the Perivascular Retinal Tissue and Acts Via an Adenosine Receptor

“…9 These purinergic compounds were initially described as intracellular signaling molecules but were later shown also to be released to act as extracellular signaling molecules. 10 Thus, extracellular purines have been shown to be important vasodilators in retinal and cerebral arterioles, 11−13 and have also been related to the development of diabetic retinopathy in experimental animals, 14,15 and in humans. 16 Prostaglandins have been shown to mediate vasodilation in cerebral arterioles after release from perivascular astrocytes, 1,3 and inhibition of cyclooxygenase (COX) has been shown to affect the tone of porcine retinal arterioles in vitro.…”