One hallmark of the adult human central nervous system is that damage is permanent. Neurons that die as a result of stroke or trauma are never replaced. In striking contrast, in the retina of adult teleost fish neuronal death stimulates neuronal regeneration and recovery of function. Our understanding of neuronal regeneration in fish is still only rudimentary. Little is known about the cellular, molecular or genetic events that underlie the ability of this animal to repair injuries to its brain. The broad objectives of the research described here are to understand in detail the cellular and molecular sequelae of neuronal injury and regeneration in the retina of the goldfish. Using both the normal and injured/regenerating retina of fish, five studies are proposed that will: 1) use organ culture and immunocytochemical techniques to identify peptide growth factors that control the proliferation of neuronal progenitors; 2) use in situ hybridization and receptor binding autoradiography techniques to identify cells that produce the peptide growth factor, insulin-like growth factor-I (IGF-I and the IGF-I receptor, respectively; 3) use in situ hybridization and immunocytochemistry to characterize the expression patterns of known retinal homeobox genes; 4) use quantitative morphometry to assess the regeneration of the foveated retina in the lemon wrass; and 5) using intracellular injections of Neurobiotin to characterize the formation of gap junctions between regenerated neurons and between regenerated neurons and extant cells in intact retina. Retinal lesions will be produced surgically by removing a small piece of retina or by intraocular injections of the metabolic poison, ouabain. Detailed knowledge about neuronal injury and retinal repair in the goldfish will contribute to our general understanding of the cellular consequences of neuronal injury in the mammalian CNS and may contribute to devising novel therapeutic approaches for treating retinal injuries in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007060-11
Application #
2414997
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1987-05-01
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
11
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Walsh, Caroline E; Hitchcock, Peter F (2017) Progranulin regulates neurogenesis in the developing vertebrate retina. Dev Neurobiol 77:1114-1129
Gramage, Esther; D'Cruz, Travis; Taylor, Scott et al. (2015) Midkine-a protein localization in the developing and adult retina of the zebrafish and its function during photoreceptor regeneration. PLoS One 10:e0121789
Taylor, Scott M; Alvarez-Delfin, Karen; Saade, Carole J et al. (2015) The bHLH Transcription Factor NeuroD Governs Photoreceptor Genesis and Regeneration Through Delta-Notch Signaling. Invest Ophthalmol Vis Sci 56:7496-515
Gramage, E; Li, J; Hitchcock, P (2014) The expression and function of midkine in the vertebrate retina. Br J Pharmacol 171:913-23
Huang, Tao; Cui, Jianlin; Li, Lei et al. (2012) The role of microglia in the neurogenesis of zebrafish retina. Biochem Biophys Res Commun 421:214-20
Taylor, Scott; Chen, Jing; Luo, Jing et al. (2012) Light-induced photoreceptor degeneration in the retina of the zebrafish. Methods Mol Biol 884:247-54
Luo, Jing; Uribe, Rosa A; Hayton, Sarah et al. (2012) Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina. Neural Dev 7:33
Thomas, Jennifer L; Ochocinska, Margaret J; Hitchcock, Peter F et al. (2012) Using the Tg(nrd:egfp)/albino zebrafish line to characterize in vivo expression of neurod. PLoS One 7:e29128
Ghosh, Amiya K; Murga-Zamalloa, Carlos A; Chan, Lansze et al. (2010) Human retinopathy-associated ciliary protein retinitis pigmentosa GTPase regulator mediates cilia-dependent vertebrate development. Hum Mol Genet 19:90-8
Craig, Sonya E L; Thummel, Ryan; Ahmed, Hafiz et al. (2010) The zebrafish galectin Drgal1-l2 is expressed by proliferating Muller glia and photoreceptor progenitors and regulates the regeneration of rod photoreceptors. Invest Ophthalmol Vis Sci 51:3244-52

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