Abstract
Tightly regulated control of cGMP levels is critical for proper functioning of photoreceptors, and mutations in cGMP synthesis or degradation factors can lead to various forms of retinal disorder. Here we review heterogenous human retinal disorders associated with mutant retinal guanylate cyclases (RetGCs) and phosphodiesterase 6 (PDE6), and describe how zebrafish are being used to examine phototransduction components and their roles in these diseases. Though mutations in RetGCs and PDE6 lead to retinal disorders, there is a lack of molecular and biochemical data on routes of subsequent photoreceptor degeneration and visual impairment. Use of animal model systems provides important information to connect in vitro biochemical analyses of mutant genes with clinically observed pathologies of human retinal diseases. Zebrafish are an excellent in vivo system to generate animal models of human retinal disorders and study photoreceptor components, and have already provided valuable data on retinal diseases caused by phototransduction component mutations.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Arshavsky VY, Lamb TD, Pugh EN Jr (2002) G proteins and phototransduction. Annu Rev Physiol 64:153–187
Chang B, Hawes NL, Hurd RE et al (2001) A new mouse model of cone photoreceptor function loss (cpfl1). IOVS 42(Suppl.):S527 (Abstract)
Chang B, Hawes NL, Hurd RE et al (2002) Retinal degeneration mutants in the mouse. Vision Res 42(4):517–525
Collery RM, Cederlund L, Smyth VA et al (2006) Applying transgenic zebrafish technology to study the retina. Adv Exp Med Biol 572:201–207
Duda T, Koch KW (2002) Retinal diseases linked with photoreceptor guanylate cyclase. Mol Cell Biochem 230(1–2):129–138
Gal A, Orth U, Baehr W et al (1994) Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness. Nat Genet 7(4):551
Gao YQ, Danciger M, Zhao DY et al (1996) Screening of the PDE6B gene in patients with autosomal dominant retinitis pigmentosa. Exp Eye Res 62(2):149–154
Goldsmith P, Harris WA (2003) The zebrafish as a tool for understanding the biology of visual disorders. Semin Cell Dev Biol 14(1):11–18
Hisatomi O, Honkawa H, Imanishi Y et al (1999) Three kinds of guanylate cyclase expressed in medaka photoreceptor cells in both retina and pineal organ. Biochem Biophys Res Commun 255(2):216–220
Huang SH, Pittler SJ, Huang X et al (1995) Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase. Nat Genet 11(4):468–471
Ionita MA, Pittler SJ (2007) Focus on molecules: rod cGMP phosphodiesterase type 6. Exp Eye Res 84(1):1–2
Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82(3):769–824
Kelsell RE, Gregory-Evans K, Payne AM et al (1998) Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy. Hum Mol Genet 7(7):1179–1184
Maddison LA, Lu J, Victoroff T, Scott E, Baier H, Chen W (2009). A gain-of-function screen in zebrafish identifies a guanylate cyclase with a role in neuronal degeneration. Mol Genet Genomics 281(5):551–563
Muto A, Orger MB, Wehman AM et al (2005) Forward genetic analysis of visual behavior in zebrafish. PLoS Genet 1(5):e66
Nishiwaki Y, Komori A, Sagara H et al (2008) Mutation of cGMP phosphodiesterase 6α'-subunit gene causes progressive degeneration of cone photoreceptors in zebrafish. Mech Dev 125(11–12):932–946
Perrault I, Rozet JM, Gerber S et al (2000) Spectrum of retGC1 mutations in Leber’s congenital amaurosis. Eur J Hum Genet 8(8):578–582
Piri N, Gao YQ, Danciger M et al (2005) A substitution of G to C in the cone cGMP-phosphodiesterase gamma subunit gene found in a distinctive form of cone dystrophy. Ophthalmology 112(1):159–166
Pugh EN Jr, Duda T, Sitaramayya A et al (1997) Photoreceptor guanylate cyclases: a review. Biosci Rep 17(5):429–473
Ramamurthy V, Tucker C, Wilkie SE et al (2001) Interactions within the coiled-coil domain of RetGC-1 guanylyl cyclase are optimized for regulation rather than for high affinity. J Biol Chem 276(28):26218–26229
22. Rätscho N, Scholten A, Scholten A et al (2009) Expression profiles of three novel sensory guanylate cyclases and guanylate cyclase-activating proteins in the zebrafish retina. Biochim Biophys Acta e-pub ahead of print
Seimiya M, Kusakabe T, Suzuki N (1997) Primary structure and differential gene expression of three membrane forms of guanylyl cyclase found in the eye of the teleost Oryzias latipes. J Biol Chem 272(37):23407–23417
Stearns G, Evangelista M, Fadool JM et al (2007) A mutation in the cone-specific pde6 gene causes rapid cone photoreceptor degeneration in zebrafish. J Neurosci 27(50):13866–13874
Tsang SH, Gouras P, Yamashita CK et al (1996) Retinal degeneration in mice lacking the gamma subunit of the rod cGMP phosphodiesterase. Science 272(5264):1026–1029
Tucker CL, Ramamurthy V, Pina AL et al (2004) Functional analyses of mutant recessive GUCY2D alleles identified in Leber congenital amaurosis patients: protein domain comparisons and dominant negative effects. Mol Vis 10:297–303
Tucker CL, Woodcock SC, Kelsell RE et al (1999) Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy. Proc Natl Acad Sci U S A 96(16):9039–9044
Vihtelic TS, Fadool JM, Gao J et al (2005) Expressed sequence tag analysis of zebrafish eye tissues for NEIBank. Mol Vis 11:1083–1100
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Collery, R.F., Kennedy, B.N. (2010). Photoreceptor Guanylate Cyclases and cGMP Phosphodiesterases in Zebrafish. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_7
Download citation
DOI: https://doi.org/10.1007/978-1-4419-1399-9_7
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-1398-2
Online ISBN: 978-1-4419-1399-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)