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Localization patterns of fibroblast growth factor 1 and its receptors FGFR1 and FGFR2 in postnatal mouse retina


Fibroblast growth factors (FGFs) exert basic functions both during embryonic development and in the adult. The expression of FGFs and their receptors has been reported in mammalian retinas, although information on the organization of the FGF system is still incomplete. Here, we report a detailed double-label immunohistochemical investigation of the localization patterns of FGF1 and its receptors FGFR1 and FGFR2 in adult and early postnatal mouse retinas. In adult retinas, FGF1 is localized to ganglion cells, horizontal cells, and photoreceptor inner and outer segments. FGFR1 is found in ganglion cells and Müller cells, whereas FGFR2 is primarily located in ganglion cells, the nuclei of Müller cells, and glycine-containing amacrine cells. During postnatal development, the patterns of FGF1, FGFR1, and FGFR2 immunostaining are similar to those in the adult, although transient FGF1-expressing cells have been detected in the proximal inner nuclear layer before eye opening. These patterns are consistent with a major involvement of FGF1, FGFR1, and FGFR2 in ganglion cell maturation (during development) and survival (in the adult). Moreover, FGF1 may affect amacrine cell development, whereas Müller cells appear to be regulated via both FGFR1 and FGFR2 throughout postnatal life. In immature retinas, large numbers of amacrine cells, including those containing calbindin and glycine, display both FGF1 and FGFR2 immunoreactivities in their nuclei, suggesting an action of FGF1 on FGFR2 leading to the maturation of these amacrine cells during a restricted period of postnatal development.

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  1. Blanco RE, Lopez-Roca A, Soto J, Blagburn JM (2000) Basic fibroblast growth factor applied to the optic nerve after injury increases long-term cell survival in the frog retina. J Comp Neurol 423:646–658

  2. Blanquet PR, Jonet L (1996) Signal-regulated proteins and fibroblast growth factor receptors: comparative immunolocalization in rat retina. Neurosci Lett 214:135–138

  3. Bottcher RT, Niehrs C (2005) Fibroblast growth factor signaling during early vertebrate development. Endocr Rev 26:63–77

  4. Bryant DM, Stow JL (2005) Nuclear translocation of cell-surface receptors: lessons from fibroblast growth factor. Traffic 6:947–954

  5. Bugra K, Hicks D (1997) Acidic and basic fibroblast growth factor messenger RNA and protein show increased expression in adult compared to developing normal and dystrophic rat retina. J Mol Neurosci 9:13–25

  6. Bugra K, Oliver L, Jacquemin E, Laurent M, Courtois Y, Hicks D (1993) Acidic fibroblast growth factor is expressed abundantly by photoreceptors within the developing and mature rat retina. Eur J Neurosci 5:1586–1595

  7. Caruelle D, Groux-Muscatelli B, Gaudric A, Sestier C, Coscas G, Caruelle JP, Barritault D (1989) Immunological study of acidic fibroblast growth factor (aFGF) distribution in the eye. J Cell Biochem 39:117–128

  8. Chai L, Morris JE (1999) Heparan sulfate in the inner limiting membrane of embryonic chicken retina binds basic fibroblast growth factor to promote axonal outgrowth. Exp Neurol 160:175–185

  9. Cinaroglu A, Ozmen Y, Ozdemir A, Ozcan F, Ergorul C, Cayirlioglu P, Hicks D, Bugra K (2005) Expression and possible function of fibroblast growth factor 9 (FGF9) and its cognate receptors FGFR2 and FGFR3 in postnatal and adult retina. J Neurosci Res 79:329–339

  10. Connolly SE, Hjelmeland LM, LaVail MM (1992) Immunohistochemical localization of basic fibroblast growth factor in mature and developing retinas of normal and RCS rats. Curr Eye Res 11:1005–1017

  11. Cornish EE, Natoli RC, Hendrickson A, Provis JM (2004) Differential distribution of fibroblast growth factor receptors (FGFRs) on foveal cones: FGFR-4 is an early marker of cone photoreceptors. Mol Vis 10:1–14

  12. Cuevas P, Carceller F, Redondo-Horcajo M, Lozano RM, Gimenez-Gallego G (1998) Systemic administration of acidic fibroblast growth factor ameliorates the ischemic injury of the retina in rats. Neurosci Lett 255:1–4

  13. Desire L, Courtois Y, Jeanny JC (2000) Endogenous and exogenous fibroblast growth factor 2 support survival of chick retinal neurons by control of neuronal neuronal bcl-x(L) and bcl-2 expression through a fibroblast berowth factor receptor 1- and ERK-dependent pathway. J Neurochem 75:151–163

  14. Dono R (2003) Fibroblast growth factors as regulators of central nervous system development and function. Am J Physiol Regul Integr Comp Physiol 284:R867–R881

  15. Fischer AJ, Reh TA (2002) Exogenous growth factors stimulate the regeneration of ganglion cells in the chicken retina. Dev Biol 251:367–379

  16. Fischer AJ, Dierks BD, Reh TA (2002) Exogenous growth factors induce the production of ganglion cells at the retinal margin. Development 129:2283–2291

  17. Fontaine V, Kinkl N, Sahel J, Dreyfus H, Hicks D (1998) Survival of purified rat photoreceptors in vitro is stimulated directly by fibroblast growth factor-2. J Neurosci 18:9662–9672

  18. Ford-Perriss M, Abud H, Murphy M (2001) Fibroblast growth factors in the developing central nervous system. Clin Exp Pharmacol Physiol 28:493–503

  19. Gao H, Hollyfield JG (1992) Basic fibroblast growth factor (bFGF) immunolocalization in the rodent outer retina demonstrated with an anti-rodent bFGF antibody. Brain Res 585:355–360

  20. Guillemot F, Cepko CL (1992) Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development. Development 114:743–754

  21. Hageman GS, Kirchoff-Rempe MA, Lewis GP, Fisher SK, Anderson DH (1991) Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix. Proc Natl Acad Sci USA 88:6706–6710

  22. Haverkamp S, Wässle H (2000) Immunocytochemical analysis of the mouse retina. J Comp Neurol 424:1–23

  23. Hicks D, Courtois Y (1992) Fibroblast growth factor stimulates photoreceptor differentiation in vitro. J Neurosci 12:2022–2033

  24. Hu DN, Ritch R (1997) Tissue culture of adult human retinal ganglion cells. J Glaucoma 6:37–43

  25. Hyer J, Mima T, Mikawa T (1998) FGF1 patterns the optic vesicle by directing the placement of the neural retina domain. Development 125:869–877

  26. Jacquemin E, Halley C, Alterio J, Laurent M, Courtois Y, Jeanny JC (1990) Localization of acidic fibroblast growth factor (aFGF) mRNA in mouse and bovine retina by in situ hybridization. Neurosci Lett 116:23–28

  27. Jacquemin E, Jonet L, Oliver L, Bugra K, Laurent M, Courtois Y, Jeanny JC (1993) Developmental regulation of acidic fibroblast growth factor (aFGF) expression in bovine retina. Int J Dev Biol 37:417–423

  28. Kinkl N, Hageman GS, Sahel JA, Hicks D (2002) Fibroblast growth factor receptor (FGFR) and candidate signaling molecule distribution within rat and human retina. Mol Vis 8:149–160

  29. Kinkl N, Ruiz J, Vecino E, Frasson M, Sahel J, Hicks D (2003) Possible involvement of a fibroblast growth factor 9 (FGF9)-FGF receptor-3-mediated pathway in adult pig retinal ganglion cell survival in vitro. Mol Cell Neurosci 23:39–53

  30. Kitaoka T, Aotaki-Keen AE, Hjelmeland LM (1994) Distribution of FGF-5 in the rhesus macaque retina. Invest Ophthalmol Vis Sci 35:3189–3198

  31. Kurose H, Bito T, Adachi T, Shimizu M, Noji S, Ohuchi H (2004) Expression of fibroblast growth factor 19 (Fgf19) during chicken embryogenesis and eye development, compared with Fgf15 expression in the mouse. Gene Expr Patterns 4:687–693

  32. Lang RA (2004) Pathways regulating lens induction in the mouse. Int J Dev Biol 48:783–791

  33. Lipton SA, Wagner JA, Madison RD, D’Amore PA (1988) Acidic fibroblast growth factor enhances regeneration of processes by postnatal mammalian retinal ganglion cells in culture. Proc Natl Acad Sci USA 85:2388–2392

  34. Lovicu FJ, Iongh RU de, McAvoy JW (1997) Expression of FGF-1 and FGF-2 mRNA during lens morphogenesis, differentiation and growth. Curr Eye Res 16:222–230

  35. Matsushima M, Ogata N, Takada Y, Tobe T, Yamada H, Takahashi K, Uyama M (1996) FGF receptor 1 expression in experimental choroidal neovascularization. Jpn J Ophthalmol 40:329–338

  36. McFarlane S, McNeill L, Holt CE (1995) FGF signaling and target recognition in the developing Xenopus visual system. Neuron 15:1017–1028

  37. McFarlane S, Cornel E, Amaya E, Holt CE (1996) Inhibition of FGF receptor activity in retinal ganglion cell axons causes errors in target recognition. Neuron 17:245–254

  38. Miyashiro M, Ogata N, Takahashi K, Matsushima M, Yamamoto C, Yamada H, Uyama M (1998) Expression of basic fibroblast growth factor and its receptor mRNA in retinal tissue following ischemic injury in the rat. Graefes Arch Clin Exp Ophthalmol 236:295–300

  39. Noji S, Matsuo T, Koyama E, Yamaai T, Nohno T, Matsuo N, Taniguchi S (1990) Expression pattern of acidic and basic fibroblast growth factor genes in adult rat eyes. Biochem Biophys Res Commun 168:343–349

  40. Ohsato M, Hayashi H, Oshima K, Koji T, Nakane P (1997) In situ localization of basic fibroblast growth factor protein and mRNA in the retina. Ophthalmic Res 29:24–30

  41. Ornitz DM, Itoh N (2001) Fibroblast growth factors. Genome Biol 2:REVIEWS3005

  42. Ozaki S, Radeke MJ, Anderson DH (2000) Rapid upregulation of fibroblast growth factor receptor 1 (flg) by rat photoreceptor cells after injury. Invest Ophthalmol Vis Sci 41:568–579

  43. Patel A, McFarlane S (2000) Overexpression of FGF-2 alters cell fate specification in the developing retina of Xenopus laevis. Dev Biol 222:170–180

  44. Picker A, Brand M (2005) Fgf signals from a novel signaling center determine axial patterning of the prospective neural retina. Development 132:4951–4962

  45. Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16:159–178

  46. Quan MZ, Kosaka M, Watanabe M, Fukuda Y (1999) Localization of FGFR-1 in axotomized and peripheral nerve transplanted ferret retina. Neuroreport 10:3903–3907

  47. Reuss B, Bohlen und Halbach O von (2003) Fibroblast growth factors and their receptors in the central nervous system. Cell Tissue Res 313:139–157

  48. Rousseau B, Larrieu-Lahargue F, Bikfalvi A, Javerzat S (2003) Involvement of fibroblast growth factors in choroidal angiogenesis and retinal vascularization. Exp Eye Res 77:147–156

  49. Russell C (2003) The roles of hedgehogs and fibroblast growth factors in eye development and retinal cell rescue. Vision Res 43:899–912

  50. Sapieha PS, Peltier M, Rendahl KG, Manning WC, Di Polo A (2003) Fibroblast growth factor-2 gene delivery stimulates axon growth by adult retinal ganglion cells after acute optic nerve injury. Mol Cell Neurosci 24:656–672

  51. Schnitzer J, Rusoff AC (1984) Horizontal cells of the mouse retina contain glutamic acid decarboxylase-like immunoreactivity during early developmental stages. J Neurosci 4:2948–2955

  52. Sievers J, Hausmann B, Unsicker K, Berry M (1987) Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve. Neurosci Lett 76:157–162

  53. Snow RL, Robson JA (1994) Ganglion cell neurogenesis, migration and early differentiation in the chick retina. Neuroscience 58:399–409

  54. Thanos S, Bahr M, Barde YA, Vanselow J (1989) Survival and axonal elongation of adult rat retinal ganglion cells. Eur J Neurosci 1:19–26

  55. Thisse B, Thisse C (2005) Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol 287:390–402

  56. Torriglia A, Jeanny JC, Blanquet PR (1994) Immunohistochemical analysis of fibroblast growth factor receptor in bovine retina. Neurosci Lett 172:125–128

  57. Unoki K, LaVail MM (1994) Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor. Invest Ophthalmol Vis Sci 35:907–915

  58. Valter K, Driel D van, Bisti S, Stone J (2002) FGFR1 expression and FGFR1-FGF-2 colocalisation in rat retina: sites of FGF-2 action on rat photoreceptors. Growth Factors 20:177–188

  59. Vogel-Hopker A, Momose T, Rohrer H, Yasuda K, Ishihara L, Rapaport DH (2000) Multiple functions of fibroblast growth factor-8 (FGF-8) in chick eye development. Mech Dev 94:25–36

  60. Wanaka A, Milbrandt J, Johnson EM Jr (1991) Expression of FGF receptor gene in rat development. Development 111:455–468

  61. Watanabe M, Rutishauser U, Silver J (1991) Formation of the retinal ganglion cell and optic fiber layers. J Neurobiol 22:85–96

  62. Webber CA, Hyakutake MT, McFarlane S (2003) Fibroblast growth factors redirect retinal axons in vitro and in vivo. Dev Biol 263:24–34

  63. Yamamoto C, Ogata N, Matsushima M, Takahashi K, Miyashiro M, Yamada H, Maeda H, Uyama M, Matsuzaki K (1996) Gene expressions of basic fibroblast growth factor and its receptor in healing of rat retina after laser photocoagulation. Jpn J Ophthalmol 40:480–490

  64. Yang XJ (2004) Roles of cell-extrinsic growth factors in vertebrate eye pattern formation and retinogenesis. Semin Cell Dev Biol 15:91–103

  65. Yeoh JS, Haan G de (2007) Fibroblast growth factors as regulators of stem cell self-renewal and aging. Mech Ageing Dev 128:17–24

  66. Zakrzewska M, Krowarsch D, Wiedlocha A, Olsnes S, Otlewski J (2006) Structural requirements of FGF-1 for receptor binding and translocation into cells. Biochemistry 45:15338–15348

  67. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM (2006) Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem 281:15694–15700

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We are grateful to Dr. Arlene Hirano (UCLA) for the NK3 antibody, to Dr. David Pow (School of Biomedical Sciences, University of Newcastle, Australia) for the glycine antibody, to Dr. Cristiano Papeschi for animal care, and to Dr. Gabriella Gambellini (Interdepartmental Center of Electron Microscopy, University of Tuscany, Italy) for help with the confocal microscopy.

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Correspondence to Giovanni Casini.

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This work was supported by funding from the Italian Ministry of Education.

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Catalani, E., Tomassini, S., Dal Monte, M. et al. Localization patterns of fibroblast growth factor 1 and its receptors FGFR1 and FGFR2 in postnatal mouse retina. Cell Tissue Res 336, 423–438 (2009).

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  • Development
  • Retinal ganglion cells
  • Amacrine cells
  • Horizontal cells
  • Müller cells
  • Mouse (C57BL/6)