Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-10T11:09:11.743Z Has data issue: false hasContentIssue false
  • English
  • Français

A gradient of basic fibroblast growth factor in rod photoreceptors in the normal human retina

Published online by Cambridge University Press:  02 June 2009

Zong-Yi Li ,
Jean H. Chang  and
Ann H. Milam
Zong-Yi Li
Affiliation:
Department of Ophthalmology, University of Washington, Seattle
Jean H. Chang
Affiliation:
Department of Ophthalmology, University of Washington, Seattle
Ann H. Milam
Affiliation:
Department of Ophthalmology, University of Washington, Seattle
Get access Rights & Permissions [Opens in a new window]

Abstract

Retinitis pigmentosa (RP) is an inherited disease that causes primary degeneration of rod photoreceptors in the retina. Although the causal gene (e.g. rhodopsin) is thought to be expressed in all rods across the retina, the degeneration is typically nonuniform, with rods in the far periphery surviving significantly longer than those in the midperiphery and macula. Basic fibroblast growth factor (bFGF) is a putative survival factor for photoreceptors, and the characteristic regional pattern of rod cell survival in RP suggested that bFGF might be distributed nonuniformly in the human retina. We performed double-label immunocytochemistry on 15 normal human retinas, using anti-bFGF and other antibody markers for retinal neurons and glia. Immunoreactivity for bFGF was consistently absent from cones but was present in rods, populations of cone bipolar and amacrine cells, Müller glial cells, and astrocytes. In the macula, the percentage of bFGF-reactive rods was very low (~0.5%) but it increased in a central to peripheral gradient, accounting for up to ~88% of the rods in the far periphery. These findings suggest that a central to peripheral gradient of rod bFGF is present in normal human retina and may influence the pattern of photoreceptor degeneration in RP. The absence of bFGF in cones and the low number of bFGF-positive rods in the macula may correlate with the vulnerability of these cells in RP, age-related macular degeneration, and other retinal diseases.

Keywords

Human retinaPhotoreceptorBasic fibroblast growth factorRetinitis pigmentosaMacular degeneration
Type
Research Articles
Information
Visual Neuroscience , Volume 14 , Issue 4 , July 1997 , pp. 671 - 679
Copyright
Copyright © Cambridge University Press 1997

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adler, R. (1996). Mechanisms of photoreceptor death in retinal degenerations. Archives of Ophthalmology 114, 79–83.CrossRefGoogle ScholarPubMed
Baird, A. (1994). Fibroblast growth factors: Activities and significance of non-neurotrophin neurotrophic growth factors. Current Opinion in Neuro-biology 4, 78–86.CrossRefGoogle ScholarPubMed
Berrebi, A.S., Oberdick, J., Sangameswaran, L., Christakos, S., Morgan, J.I. & Mugnaini, E. (1991). Cerebellar Purkinje cell markers are expressed in retinal bipolar neurons. Journal of Comparative Neurology 308, 630–649.CrossRefGoogle ScholarPubMed
Bunt-Milam, A.H. & Saari, J.C. (1983). Immunocytochemical localization of two retinoid-binding proteins in vertebrate retinas. Journal of Cell Biology 97, 703–712.CrossRefGoogle Scholar
Campochiaro, P.A., Chang, M., Ohsato, M., Vinores, S.A., Nie, Z., Hjelmeland, L., Mansukhani, A., Basilico, C. & Zack, D.J. (1996). Retinal degeneration in transgenic mice with photoreceptor-specific expression of a dominant-negative fibroblast growth factor receptor. Journal of Neuroscience 16, 1679–1688.CrossRefGoogle ScholarPubMed
Chaitin, M.H., Wortham, H.S. & Brun-Zinkernagel, A.-M. (1994). Immunocytochemical localization of CD44 in the mouse retina. Experimental Eye Research 58, 359–366.CrossRefGoogle ScholarPubMed
Connolly, S.E., Hjelmeland, L.M. & La Vail, M.M. (1992). Immuno-histochemical localization of basic fibroblast growth factor in mature and developing retinas of normal and RCS rats. Current Eye Research 11, 1005–1017.CrossRefGoogle Scholar
Crabtree, D.V., Adler, A.J. & Snodderly, D.M. (1996). Radial distribution of tocopherols in rhesus monkey retina and retinal pigment epithelium-choroid. Investigative Ophthalmology and Visual Science 37, 61–76.Google Scholar
Curcio, C.A., Medeiros, N.E. & Millican, C.L. (1996). Photoreceptor loss in age-related macular degeneration. Investigative Ophthalmology and Visual Science 37, 1236–1249.Google ScholarPubMed
Curcio, C.A., Millican, C.L., Allen, K.A. & Kalina, R.E. (1993). Aging of the human photoreceptor mosaic: Evidence for selective vulnerability of rods in central retina. Investigative Ophthalmology and Visual Science 34. 3278–3296.Google Scholar
Curcio, C.A., Sloan, K.R., Kalina, R.E. & Hendrickson, A.E. (1990). Human photoreceptor topography. Journal of Comparative Neurology 292, 497–523.CrossRefGoogle ScholarPubMed
Dryja, T.P. & Berson, E.L. (1995). Retinitis pigmentosa and allied diseases: Implications of genetic heterogeneity. Investigative Ophthalmology and Visual Science 36, 1197–1200.Google Scholar
Eisner, A., Klein, M.L., Zilis, J.D. & Watkins, M.D. (1992). Visual function and the subsequent development of exudative age-related macular degeneration. Investigative Ophthalmology and Visual Science 33, 3091–3102.Google Scholar
Faktorovich, E.G., Steinberg, R.H., Yasumura, D., Matthes, M.T. & La Vail, M.M. (1990). Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Nature 347, 83–86.CrossRefGoogle ScholarPubMed
Faktorovich, E.G., Steinberg, R.H., Yasumura, D., Matthes, M.T. & La Vail, M.M. (1992). Basic fibroblast growth factor and local injury protect photorcccptors from light damage in the rat. Journal of Neuroscience 12, 3554–3567.CrossRefGoogle ScholarPubMed
Gao, H. & Hollyfield, J. (1992). Aging of the human retina: Differential loss of neurons and retinal pigment epithelial cells. Investigative Ophthalmology and Visual Science 33, 1–17.Google Scholar
Gao, H. & Hollyfield, J.G. (1995). Basic fibroblast growth factor in retinal development: Differential levels of bFGF expression and content in normal and retinal degeneration (rd) mutant mice. Developmental Biology 169, 168–184.Google Scholar
Gao, H. & Hollyfield, J.G. (1996). Basic fibroblast growth factor: Increased gene expression in inherited and light-induced photorcccptor degeneration. Experimental Eye Research 62, 181–189.CrossRefGoogle ScholarPubMed
Gimelli, G., Maher, P., Baird, A. & Hanneken, A. (1992). Differences in the pattern of bFGF and bFGF receptor (fig) immunorcactivity in the normal human eye. Investigative Ophthalmology and Visual Science 33, 820.Google Scholar
Godbout, R., Packer, M., Poppema, S. & Dabbagh, L. (1996). Localization of cytosolic aldehyde dehydrogenase in the developing chick retina: In-situ hybridization and immunohistochcmical analyses. Developmental Dynamics 205, 319–331.3.0.CO;2-#>CrossRefGoogle Scholar
Gonzalez, A.-M., Buscaglia, M., Ong, M. & Baird, A. (1990). Distribution of basic fibroblast growth factor in the 18-day rat fetus: Localization in the basement membranes of diverse tissues. Journal of Cell Biology 110, 753–765.CrossRefGoogle ScholarPubMed
Grothe, C., Zachmann, K. & Unsicker, K. (1991). Basic FGF-like immunorcactivity in the developing and adult rat brainstem. Journal of Comparative Neurology 305, 328–336.CrossRefGoogle ScholarPubMed
Grünert, U., Martin, P.R. & Wässle, H. (1994). Immunocytochemical analysis of bipolar cells in the macaque monkey retina. Journal of Comparative Neurology 348, 607–627.CrossRefGoogle ScholarPubMed
Hageman, G.S., Kirchoff-Rempe, M.A., Lewis, G.P., Fisher, S.K. & Anderson, D.H. (1991). Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix. Proceedings of the National Academy of Sciences of the U.S.A. 88, 6706–6710.Google Scholar
Haley, T.L., Pochet, R., Baizer, L., Burton, M.D., Crabb, J.W., Parmentier, M. & Polans, A.S. (1995). Calbindin D-28K immuno-reactivity of human cone cells varies with retinal position. Visual Neuroscience 12, 301–307.Google Scholar
Hanneken, A. & Baird, A. (1992). Immunolocalization of basic fibroblast growth factor: Dependence on antibody type and tissue fixation. Experimental Eye Research 54, 1011–1014.Google Scholar
Hanneken, A., De Juan, E., Lutty, G.A., Fox, G.M., Schiffer, S. & Hjelmeland, L.M. (1991). Altered distribution of basic fibroblast growth factor in diabetic retinopathy. Archives of Ophthalmology 109, 1005–1011.CrossRefGoogle ScholarPubMed
Hatten, M.E., Lynch, M., Rydel, R.E., Sanchez, J., Joseph-Silverstein, J., Moscatelli, D. & Rifkin, D.B. (1988). In-vitro neurite extension by granule neurons is dependent upon astroglial-derived fibroblast growth factor. Developmental Biology 125, 280–289.Google Scholar
Huang, P.C., Gaitan, A.E., Hao, Y., Peters, R.M. & Wong, F. (1993). Cellular interactions implicated in the mechanism of photoreceptor degeneration in transgenic mice expressing a mutant rhodopsin gene. Proceedings of the National Academy of Sciences of the U.S.A. 90. 8484–8488.Google Scholar
Jacobson, S.G., Kemp, C.M., Sung, C.-H. & Nathans, J. (1991). Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations. American Journal of Ophthalmology. 112, 256–271.Google Scholar
Kaplan, M.W., Sterrett, C.B., Morrison, R.S. & Siordano, S.C. (1992). Nuclear localization of basic fibroblast growth factor immunorcactivity in human retinal neurons. Investigative Ophthalmology and Visual Science 33, 820.Google Scholar
Kitaoka, T., Aotaki-Keen, A.E. & Hjelmeland, L.M. (1994). Distribution of FGF-5 in the rhesus macaque retina. Investigative Ophthalmology and Visual Science 35, 3189–3198.Google Scholar
Kondo, H., Takahashi, H. & Takahashi, Y. (1984). Immunohistochemical study of S100 protein in the postnatal development of Müller cells and astrocytes in the rat retina. Cell and Tissue Research 238. 503–508.CrossRefGoogle ScholarPubMed
Kostyk, S.K., D'Amore, P.A., Herman, I.M. & Wagner, J.A. (1994). Optic nerve injury alters basic fibroblast growth factor localization in the retina and optic tract. Journal of Neuroscience 14, 1441–1449.Google Scholar
La Vail, M.M., Ukoki, K., Yasumura, D., Matthes, M.T., Yancopoulos, G.D. & Steinberg, R.H. (1992). Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proceedings of the National Academy of Sciences of the U.S.A. 89, 11249–11254.Google Scholar
La Vail, M.M., Yasumura, D., Faktorovich, E.G., Hepler, I.M., Matthes, M.T., Pearson, K.L. & Steinberg, R.H. (1991). Basic fibroblast growth factor protects photoreceptors from light induced degeneration in albino rats. Annals of the New York Academy of Sciences 638, 1341–1347.Google ScholarPubMed
Li, Z.-Y., Jacobson, S.G. & Milam, A.H. (1994). Autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation: Retinal histopathology and immunocytochemistry. Experimental Eye Research 58, 397–408.Google Scholar
Li, Z.-Y., Kljavin, I.J. & Milam, A.H. (1995). Rod photoreceptor neurite sprouting in retinitis pigmentosa. Journal of Neuroscience 15, 5429–5438.Google Scholar
Linser, P. & Moscona, A.A. (1981). Carbonic anhydrase C in the neural retina: Transition from generalized to glia-specific cell localization during embryonic development. Proceedings of the National Academy of Sciences of the U.S.A. 78, 7190–7194.Google Scholar
Logan, A., Frautschy, S.A., Gonzalez, A.M. & Baird, A. (1992). A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (fig) following a localized cortical brain injury. Journal of Neuroscience 12, 3828–3837.CrossRefGoogle Scholar
Martin, P.R. & Grünert, U. (1992). Spatial density and immunoreactivity of bipolar cells in the macaque monkey retina. Journal of Comparative Neurology 323, 268–278.Google Scholar
Massof, R.W. & Finkelstein, D. (1979). Rod sensitivity relative to cone sensitivity in retinitis pigmentosa. Investigative Ophthalmology and Visual Science 18, 263–272.Google ScholarPubMed
Masuda, K., Watanabe, I., Unoki, K., Ohba, N. & Muramatsu, T. (1995). Functional rescue of photoreceptors from the damaging effects of constant light by survival-promoting factors in the rat. Investigative Ophthalmology and Visual Science 36, 2142–2146.Google Scholar
Mattson, M.P. & Scheff, S.W. (1994). Endogenous neuroprotection factors and traumatic brain injury: Mechanisms of action and implications for therapy. Journal of Neurotrauma 11, 3–33.Google Scholar
McCaffery, P., Posch, K.C., Napoli, J.L., Gudas, L. & Dräger, U.C. (1993). Changing patterns of the retinoic acid system in the developing retina. Developmental Biology 158, 390–399.CrossRefGoogle Scholar
McFarlane, S., McNeill, L. & Holt, C.E. (1995). FGF signaling and target recognition in the developing Xenopus visual system. Neuron 15, 1017–1028.Google Scholar
Milam, A.H. (1993). Strategies for rescue of retinal photoreceptor cells. Current Opinion in Neurobiology 3, 797–804.CrossRefGoogle ScholarPubMed
Milam, A.H., Dacey, D.M. & Dizhoor, A.M. (1993). Recoverin immu-noreactivity in mammalian cone bipolar cells. Visual Neuroscience 10, 1–12.Google Scholar
Milam, A.H. & Jacobson, S.G. (1990). Photoreceptor rosettes with blue cone opsin immunoreactivity in retinitis pigmentosa. Ophthalmology 97, 1620–1631.CrossRefGoogle ScholarPubMed
Milam, A.H., Li, Z.-Y., Cideciyan, A.V. & Jacobson, S.G. (1996). Clinico-pathologic effects of the Q64ter rhodopsin mutation in retinitis pigmentosa. Investigative Ophthalmology and Visual Science 37, 753–765.Google Scholar
Naash, M.I., Peachey, N.S., Li, Z.-Y., Gryczan, C.C., Goto, Y., Blanks, J., Milam, A.H. & Ripps, H. (1996). Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant opsin. Investigative Ophthalmology and Visual Science 37, 775–782.Google Scholar
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. Biochemical and Biophysical Research Communication 168, 343–349.CrossRefGoogle ScholarPubMed
Papermaster, D.S. (1995). Necessary but insufficient. Nature Medicine 1, 874–875.Google Scholar
Perry, J., Du, J., Kjeldbye, H. & Gouras, P. (1995). The effects of bFGF on RCS rat eyes. Current Eye Research 14, 585–592.Google Scholar
Raymond, P.A., Barthel, L.K. & Rounsifer, M.E. (1992). Immuno-localization of basic fibroblast growth factor and its receptor in adult goldfish retina. Experimental Neurology 115, 73–78.Google Scholar
Sanes, J.R. (1993). Topographic maps and molecular gradients. Current Opinion in Neurobiology 3, 67–74.CrossRefGoogle ScholarPubMed
Schlosshauer, B., Blum, A.S., Mendez-Otero, R., Barnstable, C.J. & Constantine-Paton, M. (1988). Developmental regulation of gan-glioside antigens recognized by the JONES antibody. Journal of Neuroscience 8, 580–592.CrossRefGoogle ScholarPubMed
Schlötzer-Schrehardt, U. & Dörfler, S. (1993). Immunolocalization of growth factors in the human ciliary body epithelium. Current Eye Research 12, 893–905.Google Scholar
Spencer, W.H., ed. (1985). Ophthalmic Pathology Vol. II. Philadelphia, Pennsylvania: W. B. Saunders pp. 814–818.Google Scholar
Steinmetz, R.L., Haimovici, R., Jubb, C., Fitzke, F.W. & Bird, A.C. (1993). Symptomatic abnormalities of dark adaptation in patients with age-related Bruch's membrane change. British Journal of Ophthalmology 77, 549–554.Google Scholar
Walicke, P.A. (1988). Interactions between basic fibroblast growth factor (FGF) and glycosaminoglycans in promoting neurite outgrowth. Experimental Neurology 102, 144–148.Google Scholar
Wen, R., Song, Y., Cheng, T., Matthes, M.T., Uasumura, D., La Vail, M.M. & Steinberg, R.H. (1995). Injury-induced upregulation of bFGF and CNTF mRNAs in the rat retina. Journal of Neuroscience 15, 7377–7385.Google Scholar
Woodward, W.R., Nishi, R., Meshul, C.K., Williams, T.E., Coulombre, M. & Eckenstein, F.P. (1992). Nuclear and cytoplasmic localization of basic fibroblast growth factor in astrocytes and CA2 hippocampal neurons. Journal of Neuroscience 12, 142–152.Google Scholar