Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo.
The P2X(7) receptor is associated with the death of many cell types, and growing evidence supports its presence on neurons. Activation of the P2X(7) receptor on isolated retinal ganglion cells increases intracellular calcium levels and can kill the cells. Within the intact eye, however, glia and other cell types surrounding the ganglion cells may provide protection and attenuate the effects of receptor stimulation. This investigation thus asks whether stimulation of the P2X(7) receptor can actually kill retinal ganglion cells in vivo. Drugs were injected intravitreally into the superior/nasal region of Long Evans rats. Cell survival was determined by counting the number of remaining ganglion cells labeled with aminostilbamidine. The P2X(7) receptor agonist BzATP reduced ganglion cell survival as compared to eyes injected with saline solution. Ganglion cell death was inhibited by co-injection of the P2X(7) antagonists Brilliant Blue G and MRS 2540. The loss of ganglion cells following activation of the P2X(7) receptor was also prevented by the adenosine A(3) adenosine receptor agonist MRS 3558. In conclusion, stimulation of the P2X(7) receptor can kill retinal ganglion cells in vivo. The neuroprotective effects of A(3) receptor activation identified in isolated ganglion cells are also apparent in vivo. This implies that the balance between extracellular ATP and its protective metabolite adenosine can influence ganglion cell survival in the living eye.
Hu
Huiling
H
Department of Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA.
Lu
Wennan
W
Zhang
Mei
M
Zhang
Xiulan
X
Argall
Arthur J
AJ
Patel
Shaun
S
Lee
Ga Eun
GE
Kim
Yong-Chul
YC
Jacobson
Kenneth A
KA
Laties
Alan M
AM
Mitchell
Claire H
CH
D058909:Adenosine A3 Receptor Agonists; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D001557:Benzenesulfonates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D007267:Injections; D010879:Piperazines / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D012394:Rosaniline Dyes / Q000494:pharmacology; D014822:Vitreous Body
C552211:4-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo(3.1.0)hexane-1-carboxamide; C552212:4-(3-(4-benzoylpiperazin-1-yl)-2-(benzyloxycarbonylamino)-3-oxopropyl)-3,5-dimethylphenyl 4-methylbenzenesulfonate; D058909:Adenosine A3 Receptor Agonists; D017304:Annexin A5; D001557:Benzenesulfonates; C546470:P2rx7 protein, rat; D010879:Piperazines; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; C004692:coomassie Brilliant Blue; D002118:Calcium