It is well recognized that the photoreceptor synaptic terminal responds to injury and disease by making structural changes. In retinal detachment the rod axon retracts toward the cell body whereas in human and animal retinal degenerations, the photoreceptors grow long neurites or make new synapses with other retinal cells. Whether these changes are harmful or helpful in disease is unknown but these changes do hold out promise that retinal transplantation is possible since they show that photoreceptor synapses are capable of structural plasticity. This application examines the mechanisms involved in synaptic changes in amphibian and mammalian photoreceptor cells and has the following specific aims: 1) to identify the signaling pathways which control axonal plasticity in rod and cone cells; 2) to determine the preferred synaptic targets for photoreceptors and the influence of Muller cells on synaptogenesis; and 3) to translate the results from amphibian photoreceptors to the mammalian retina. Rod and cone photoreceptors will be treated with agonists and antagonists of cyclic nucleotide signaling pathways and examined with immunocytochemistry and confocal laser scanning microscopy to test the hypothesis that rod and cone cells use cAMP- and cGMP-dependent pathways respectively to stimulate structural change. Creation of groups of retinal neurons by micromanipulation with optical tweezers, followed by conventional and video time lapse microscopy will test potential attractive and repulsive forces during the formation of new synapses. And results which demonstrate optimal growth and synapse formation will then be tested on sheets of photoreceptors prepared for transplantation. These projects explore the fundamental mechanisms involved in the plasticity of the photoreceptor synapse after injury and hope to provide a rational basis for future repair of the retina by manipulation of endogenous cellular activities and/or transplantation of neurons.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012031-08
Application #
6910617
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Mariani, Andrew P
Project Start
1998-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
8
Fiscal Year
2005
Total Cost
$349,875
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Neurosciences
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
Kung, Frank; Wang, Weiwei; Tran, Tracy S et al. (2017) Sema3A Reduces Sprouting of Adult Rod Photoreceptors In Vitro. Invest Ophthalmol Vis Sci 58:4318–4331
Kung, Frank; Wang, Jianfeng; Perez-Castillejos, Raquel et al. (2015) Position along the nasal/temporal plane affects synaptic development by adult photoreceptors, revealed by micropatterning. Integr Biol (Camb) 7:313-23
Shrirao, Anil B; Kung, Frank H; Yip, Derek et al. (2014) Vacuum-assisted fluid flow in microchannels to pattern substrates and cells. Biofabrication 6:035016
Wang, Jianfeng; Zhang, Nan; Beuve, Annie et al. (2012) Mislocalized opsin and cAMP signaling: a mechanism for sprouting by rod cells in retinal degeneration. Invest Ophthalmol Vis Sci 53:6355-69
Han, Jianzhong; Townes-Anderson, Ellen (2012) Cell specific post-translational processing of pikachurin, a protein involved in retinal synaptogenesis. PLoS One 7:e50552
Fontainhas, Aurora Maria; Townes-Anderson, Ellen (2011) RhoA inactivation prevents photoreceptor axon retraction in an in vitro model of acute retinal detachment. Invest Ophthalmol Vis Sci 52:579-87
Wang, Jianfeng; Kolomeyer, Anton M; Zarbin, Marco A et al. (2011) Organotypic culture of full-thickness adult porcine retina. J Vis Exp :
Fontainhas, Aurora M; Townes-Anderson, Ellen (2008) RhoA and its role in synaptic structural plasticity of isolated salamander photoreceptors. Invest Ophthalmol Vis Sci 49:4177-87
Clarke, Robert J; Hognason, Kormakur; Brimacombe, Michael et al. (2008) Cone and rod cells have different target preferences in vitro as revealed by optical tweezers. Mol Vis 14:706-20
Khodair, Mohamad A; Zarbin, Marco A; Townes-Anderson, Ellen (2005) Cyclic AMP prevents retraction of axon terminals in photoreceptors prepared for transplantation: an in vitro study. Invest Ophthalmol Vis Sci 46:967-73

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