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The Journal of Neuroscience, November 2, 2005, 25(44):10157-10166; doi:10.1523/JNEUROSCI.3247-05.2005

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Development/Plasticity/Repair
Glucagon-Expressing Neurons within the Retina Regulate the Proliferation of Neural Progenitors in the Circumferential Marginal Zone of the Avian Eye

Andy J. Fischer,¹ Ghezal Omar,¹ Nathaniel A. Walton,² Thomas A. Verrill,¹ and Cecilia G. Unson³

¹Department of Neuroscience and ²The Graduate Program in Molecular, Cellular and Developmental Biology, The Ohio State University, Columbus, Ohio 43210-1239, and ³Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, New York, New York 10021

Glucagon-expressing retinal amacrine cells have been implicated in regulating postnatal ocular growth. Furthermore, experimentally accelerated rates of ocular growth increase the number of neurons added to the peripheral edge of the retina. Accordingly, we assayed whether glucagon-expressing neurons within the retina regulate the proliferation of progenitors in the circumferential marginal zone (CMZ) of the postnatal chicken eye. We found that glucagon-containing neurites are heavily clustered within the CMZ at the peripheral edge of the retina. Many of these neurites originate from a cell type that is distinct from other types of retinal neurons, which we termed large glucagon-expressing neurons (LGENs). The LGENs are immunoreactive for glucagon and glucagon-like peptide 1 (GLP1), have a unipolar morphology, produce an axon that projects into the CMZ, and are found only in ventral regions of the retina. In dorsal regions of the retina, a smaller version of the LGENs densely ramifies neurites in the CMZ. Intraocular injections of glucagon or GLP1 suppressed the proliferation of progenitors in the CMZ, whereas a glucagon-receptor antagonist promoted proliferation. In addition, we found that glucagon, GLP1, and glucagon antagonist influenced the number of progenitors in the CMZ. We conclude that the LGENs may convey visual information to the CMZ to control the addition of new cells to the edge of the retina. We propose that glucagon/GLP1 released from LGENs acts in opposition to insulin (or insulin-like growth factor) to regulate precisely the proliferation of retinal progenitors in the CMZ.

Key words: retina; glucagon; proliferation; progenitor; stem cell; insulin

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Received Aug 3, 2005; revised September 19, 2005; accepted September 23, 2005.

This article has been cited by other articles:

				P. E. B. Nickerson, J. G. Emsley, T. Myers, and D. B. Clarke Proliferation and Expression of Progenitor and Mature Retinal Phenotypes in the Adult Mammalian Ciliary Body after Retinal Ganglion Cell Injury Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5266 - 5275. [Abstract] [Full Text] [PDF]

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