Pearson, Rachael A.; (2002) The role of neurotransmitters in the regulation of cell proliferation in the embryonic chick retina. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis investigates the roles of neurotransmitters and their receptors, changes in intracellular calcium ([Ca2+]i), and the retinal pigment epithelium (RPE) in the regulation of cell proliferation and migration in the developing chick retina. Confocal imaging of retinae is used to show that before synapses are formed, cells in the ventricular zone (VZ) display intermittent spontaneous [Ca2+]i transients that depend upon the endogenous release of neurotransmitters. Purinergic and muscarinic receptor- evoked transients occur in a mixed population of interphase and mitotic cells. Those produced by GABAergic and glutamatergic receptors are mostly restricted to the interphase population. Muscarinic receptor activation is shown to slow down, and purinergic activation to speed up, mitosis. These actions may result from the [Ca2+]i transients these agonists evoke. GABA and glutamate receptor activation are without effect on mitosis. The nuclei of retinal progenitor cells (PCs) migrate back-and-forth across the retina in a process called interkinetic nuclear migration (INM). To study the possible influence of neurotransmitter receptor activation on INM, a 'gene gun' technique was used to label cells in the VZ; the speed of movement of some cells is influenced by neurotransmitters. [Ca2+]i transients occur in cells during INM, which may be important in its regulation. Gap junctional communication between the RPE and the neural retina was investigated. Ca2+ -imaging experiments show that gap junctions support the spread of spontaneous Ca2+ signals between neighbouring cells. Whole-cell patch clamp recording was used to fill VZ cells with a combination of gap junction-permeable and impermeable dyes. These injections show that gap junctions couple PCs into clusters that largely exclude differentiated neurons. Coupling was also observed between cells in the RPE and the neural retina. These pathways may be important in the regulation of proliferation. The RPE is shown to express both purinergic and muscarinic receptors and to have a profound influence on the rate of cell proliferation in the neural retina. The RPE may speed mitosis in the retina through the release of ATP and other factors.

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