ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation.
The retinal pigment epithelium (RPE) plays an essential role in the normal development of the underlying neural retina, but the mechanisms by which this regulation occurs are largely unknown. Ca2+ transients, induced by the neurotransmitter ATP acting on purinergic receptors, both increase proliferation and stimulate DNA synthesis in neural retinal progenitor cells. Here, we show that the RPE regulates proliferation in the underlying neural retina by the release of a soluble factor and identify that factor as ATP. Further, we show that this ATP is released by efflux through gap junction connexin 43 hemichannels, the opening of which is evoked by spontaneous elevations of Ca2+ in trigger cells in the RPE. This release mechanism is localized within the RPE cells to the membranes facing the neural retina, a location ideally positioned to influence neural retinal development. ATP released from RPE hemichannels speeds both cell division and proliferation in the neural retina.
Pearson
Rachael A
RA
Department of Physiology, University College London, Gower Street, London WC1E 6BT, United Kingdom. rachael.pearson@ich.ucl.ac.uk
Dale
Nicholas
N
Llaudet
Enrique
E
Mobbs
Peter
P
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology
D013498:Suramin; D000255:Adenosine Triphosphate