References

Arikawa K, Molday LL, Molday RS et al (1992) Localization of peripherin/rds in the disk membranes of cone and rod photoreceptors: relationship to disk membrane morphogenesis and retinal degeneration. J Cell Biol 116:659

Batra-Safferling R, Abarca-Heidemann K, Korschen HG et al (2006) Glutamic acid-rich proteins of rod photoreceptors are natively unfolded. J Biol Chem 281:1449

Boesze-Battaglia K (2000) Fusion between retinal rod outer segment membranes and model membranes: functional assays and role for peripherin/rds. Methods Enzymol 316:65

Boesze-Battaglia K, Song H, Sokolov M et al (2007) The tetraspanin protein peripherin-2 forms a complex with melanoregulin, a putative membrane fusion regulator. Biochemistry 46:1256 Chaitin MH, Carlsen RB, Samara GJ (1988) Immunogold localization of actin in developing

photoreceptor cilia of normal and rds mutant mice. Exp Eye Res 47:437

Chakraborty D, Ding XQ, Fliesler SJ et al (2008) Outer segment oligomerization of rds: evidence from mouse models and subcellular fractionation. Biochemistry 47:1144

Cheng T, Peachey NS, Li S et al (1997) The effect of peripherin/rds haploinsufficiency on rod and cone photoreceptors. J Neurosci 17:8118

Colville CA, Molday RS (1996) Primary structure and expression of the human beta-subunit and related proteins of the rod photoreceptor cGMP-gated channel. J Biol Chem 271:32968

Daniele LL, Lillo C, Lyubarsky AL et al (2005) Cone-like morphological, molecular, and electrophysiological features of the photoreceptors of the Nrl knockout mouse. Invest Ophthalmol Vis Sci 46:2156

Farjo Q, Jackson A, Pieke-Dahl S et al (1997) Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration. Genomics 45:395

Farjo Q, Jackson AU, Xu J et al (1993) Molecular characterization of the murine neural retina leucine zipper gene, Nrl. Genomics 18:216

Goldberg AF, Molday RS (2000) Expression and characterization of peripherin/rds-rom-1 complexes and mutants implicated in retinal degenerative diseases. Methods Enzymol 316:671 Goldberg AF, Moritz OL, Molday RS (1995) Heterologous expression of photoreceptor periph-

erin/rds and Rom-1 in COS-1 cells: assembly, interactions, and localization of multisubunit complexes. Biochemistry 34:14213

Hawkins RK, Jansen HG, Sanyal S (1985) Development and degeneration of retina in rds mutant mice: photoreceptor abnormalities in the heterozygotes. Exp Eye Res 41:701

Hemler ME (2003) Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 19:397

Kaupp UB, Niidome T, Tanabe T et al (1989) Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342:762

Korschen HG, Beyermann M, Muller F et al (1999) Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors. Nature 400:761

Levy S, Shoham T (2005) Protein-protein interactions in the tetraspanin web. Physiology (Bethesda) 20:218

Matveev AV, Quiambao AB, Browning Fitzgerald J et al (2008) Native cone photoreceptor cyclic nucleotide-gated channel is a heterotetrameric complex comprising both CNGA3 and CNGB3: a study using the cone-dominant retina of Nrl–/– mice. J Neurochem 106:2042

Mears AJ, Kondo M, Swain PK et al (2001) Nrl is required for rod photoreceptor development. Nat Genet 29:447

Mitton KP, Swain PK, Chen S et al (2000) The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation. J Biol Chem 275:29794

Moritz OL, Peck A, Tam BM (2002) Xenopus laevis red cone opsin and Prph2 promoters allow transgene expression in amphibian cones, or both rods and cones. Gene 298:173

Nikonov SS, Daniele LL, Zhu X et al (2005) Photoreceptors of Nrl –/– mice coexpress functional S- and M-cone opsins having distinct inactivation mechanisms. J Gen Physiol 125:287

Picones A, Korenbrot JI (1995) Spontaneous, ligand-independent activity of the cGMP-gated ion channels in cone photoreceptors of fish. J Physiol 485 (Pt 3):699

Poetsch A, Molday LL, Molday RS (2001) The cGMP-gated channel and related glutamic acidrich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes. J Biol Chem 276:48009

Pugh EN (2000) Handbook of biological physics. Elsevier/North-Holland, Amsterdam Rehemtulla A, Warwar R, Kumar R et al (1996) The basic motif-leucine zipper transcription factor

Nrl can positively regulate rhodopsin gene expression. Proc Natl Acad Sci USA 93:191

Roof DJ, Heuser JE (1982) Surfaces of rod photoreceptor disk membranes: integral membrane components. J Cell Biol 95:487

Sanyal S, De Ruiter A, Hawkins RK (1980) Development and degeneration of retina in rds mutant mice: light microscopy. J Comp Neurol 194:193

Sanyal S, Dees C, Zeilmaker GH (1986) Development and degeneration of retina in rds mutant mice: observations in chimaeras of heterozygous mutant and normal genotype. J Embryol Exp Morphol 98:111

Sanyal S, Zeilmaker GH (1984) Development and degeneration of retina in rds mutant mice: light and electron microscopic observations in experimental chimaeras. Exp Eye Res 39:231

Stipp CS, Kolesnikova TV, Hemler ME (2003) Functional domains in tetraspanin proteins. Trends Biochem Sci 28:106

Swaroop A, Xu JZ, Pawar H et al (1992) A conserved retina-specific gene encodes a basic motif/leucine zipper domain. Proc Natl Acad Sci USA 89:266

Chapter 9

Increased Expression of TGF-β1 and Smad 4 on

Oxygen-Induced Retinopathy in Neonatal Mice

Fan Yingchuan, Lei Chuntao, Chen Hui, and Hu Jianbin

Abstract Retinal neovascularization (NV) is a major cause of the blindness associated with such ischemic retinal disorders as diabetic retinopathy, retinopathy of prematurity and retinal occlusion. Neovascularization is induced by complex interactions among growth factors and cytokines. Some studies confirm that VEGF play a central role in neovascularization, there remain some questions as to why VEGF antagonists are only partially effective. Transforming growth factor-β (TGF-β) has been implicated in the development of neovascularization (Gerard et al. 2000). Smad 4 plays the most important role in the TGF-β signal transduction (Zimowska 2006). In this study, we used the model of oxygen-induced retinopathy in neonatal mice to investigate the expression of TGF-β1 and Smad 4 mRNA in the retina, to explore their role in the development of retinal neovascularization.

9.1 Introduction

Retinal neovascularization (NV) is a major cause of the blindness associated with such ischemic retinal disorders as diabetic retinopathy, retinopathy of prematurity and retinal occlusion. Neovascularization is induced by complex interactions among growth factors and cytokines. Some studies confirm that VEGF play a central role in neovascularization, there remain some questions as to why VEGF antagonists are only partially effective. Transforming growth factor-β (TGF-β) has been implicated in the development of neovascularization (Gerard et al. 2000). Smad 4 plays the most important role in the TGF-β signal transduction (Zimowska 2006). In this study, we used the model of oxygen-induced retinopathy in neonatal mice to

L. Chuntao and C. Hui (B)

Department of Ophthalmology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 610072, China

e-mail: hblct@163.com; chenhuicq@yahoo.com.cn

Medicine and Biology 664, DOI 10.1007/978-1-4419-1399-9_9,

C Springer Science+Business Media, LLC 2010