Skip to main content
SpringerLink
Log in

Defective Choroidal Angiogenesis Precedes Retinal Pigment Epithelial Phagocytic Defect in Neonatal Rcs Rats

  • Chapter
Degenerative Retinal Diseases

  • 114 Accesses

Abstract

The well known defect in phagocytosis of rod outer segment (ROS) membranes by the retinal pigment epithelium (RPE) of RCS rats, the subject of numerous investigations, has long been considered to be the primary pathology leading to retinal degeneration in this mutant (1–3). Light microscopic and ultrastructural studies of the developing photoreceptors of these animals have determined that the phagocytic defect is first evident around postnatal day 12, coincident with the onset of retinal phagocytosis in the normal animals (4). Recently, our laboratory has provided evidence that there is a second defect in dystrophic rat eyes that appears earlier in development than the phagocytic defect: this abnormality involves failed or delayed development of the choroidal vasculature, which normally proceeds rapidly between postnatal days 7–10 (5). In this chapter, I briefly review the data revealing the choroidal angiogenesis defect in mutant RCS rat pups, as well as our recent evidence indicating a reduction in the mRNA and protein for basic fibroblast growth factor (bFGF) in intact RPE of neonatal RCS rats (5). This new data is discussed in the context of previous conflicting investigations into bFGF expression in RCS rat retinas. Finally, the hypothesis is explored that the observed downregulation of bFGF in the mutant RPE during this period in postnatal ocular development may play a central role in the pathology, adversely affecting choroidal angiogenesis, RPE phagocytic function and trophic support of the photoreceptors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Herron, W.L., Reigel, B.W., Myers, O.E., and Rubin. M.L., 1969, Retinal dystrophy in the rat-a pigment epithelial disease, Invest. Ophthalmol Vis. Sci. 8:595–604.

    CAS  Google Scholar 

  2. Bok, D., and Hall, M.O., 1971, The role of the pigment epithelium in the etiology of inherited retinal dys trophy in the rat, J. Cell Biol. 49:664–682.

    Article  PubMed  CAS  Google Scholar 

  3. Edwards, R.B., and Szamier, R.B., 1977, Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture, Science 197:1001–1003.

    Article  PubMed  CAS  Google Scholar 

  4. Irons, M.J., 1989, Localization of 5′-nucleotidase activity in RCS rat retinas, in: Inherited and Environ mentally Induced Retinal Degenerations, (M.M. LaVail, R.E. Anderson, and J.G. Hollyfield, eds.), pp. 301–314, Alan R, Liss, New York.

    Google Scholar 

  5. McLaren, M.J., An. W., Brown, M.E., and Inana, G, 1996, Analysis of basic fibroblast growth factor in rats with inherited retinal degeneration, FEBS Lett. 387:63–70.

    Article  PubMed  CAS  Google Scholar 

  6. McLaren, M.J., Sasabe, T., Li, C.-Y., Brown, M.E., and Inana, G., 1993, Spontaneously arising immortal cell line of rat retinal pigmented epithelial cells, Exp. Cell Res. 204:311–320.

    Article  PubMed  CAS  Google Scholar 

  7. Berson, D., 1965, The development of the choroid and sciera in the eye of the foetal rat with particular ref erence to their developmental interrelationship, Exp. Eye Res. 4:102–103.

    Article  Google Scholar 

  8. Braekevelt, C.R., and Hollenberg, M.J., 1970, Development of the retinal pigment epithelium, choriocapil laris and bruch’s membrane in the albino rat, Exp. Eye Res. 9:124–131.

    Article  PubMed  CAS  Google Scholar 

  9. Faktorovich, E.G., Steinberg, R.H., Yasamura, D., Matthes, M.T., and LaVail, M.M., 1990, Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor, Nature 347:83–86.

    Article  PubMed  CAS  Google Scholar 

  10. Connolly, S.E., Hjelmeland, L.M., and LaVail, M.M, 1992, Immunohistochemical localization of basic fi broblast growth factor in mature and developing retinas of normal and RCS rats. Curt: Eye Res. 11:1005–1017.

    Article  CAS  Google Scholar 

  11. Rakoczy, P.E., Humphrey, M.F., Cavaney, D.M., Chu, Y., and Constable, I.J., 1993, Expression of basic fi broblast growth factor and its receptor in the retina of Royal College of Surgeons rats. A comparative study, Invest. Ophthamol. Vis. Sci. 34:1845–1852.

    CAS  Google Scholar 

  12. Malecaze, F., Mascarelli, F., Bugra, K., Fuhrmann, G., Courtois, Y., and Hicks, D, 1993, Fibroblast growth factor receptor deficiency in dystrophic retinal pigment epithelium. J. Cell. Physiol. 154:631–642.

    Article  PubMed  CAS  Google Scholar 

  13. Mullen, R.J., and LaVail, M.M., 1976, Inherited retinal dystrophy. Primary defect in pigment epithelium determined with experimental rat chimeras. Science 192:799–801.

    Article  PubMed  CAS  Google Scholar 

  14. Irons, M.J., 1987, Redistribution of Mn++-dependent pyrimidine 5′-nucleotidase (MDPNase) activity dur ing shedding and phagocytosis, Invest. Ophthalmol. Vis. Sci. 28:83–91.

    PubMed  CAS  Google Scholar 

  15. McLaren, M.J., Inana, G., and Li, C.-Y, 1993, Double fluorescent vital assay of phagocytosis by cultured retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 34:317–326.

    PubMed  CAS  Google Scholar 

  16. McLaren, M.J., 1996, Kinetics of rod outer segment phagocytosis by cultured retinal pigment epithelial cells. Relationship to cell morphology. Invest. Ophthalmol. Vis. Sci. 37:1213–1224.

    PubMed  CAS  Google Scholar 

  17. McLaren, M.J., and Inana, G., 1995, ROS phagocytosis by cultured normal rat RPE and bFGF-treated dys trophic RPE is transcriptionally controlled. Invest. Ophthalmol. Vis. Sci. 36(4): S815.

    Google Scholar 

  18. Gospodarowicz, D., Ferrara, N., Schweigerer, L., and Neufeld. G, 1987, Structural characterization and biological functions of fibroblast growth factor. Endocrine Rev. 8:95–114.

    Article  CAS  Google Scholar 

  19. LaVail, M.M., 1979, The retinal pigment epithelium in mice and rats with inherited retinal degeneration, in: The Retinal Pigment Epithelium, (K.M. Zinn, and M.F. Marmor, eds.), pp. 357–380. Harvard University Press, Cambridge, Massachusetts.

    Google Scholar 

  20. Roque, R.S., and Caldwell, R.B., 1991, Pigment epithelial cell changes precede vascular transformations in the dystrophic retina, Exp. Eye Res. 28:787–798.

    Article  Google Scholar 

  21. Fitzgerald, M.E., Caldwell, R.B., and Reiner, A., 1992, Vasoactive intestinal polypeptide-containing nerve fibers are increased in abundance in the choroid of dystrophic RCS rats. Curr. Eye Res. 11: 501–515.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Florkiewicz, R.Z., and Sommer, A., 1989, Human fibroblast growth factor gene encodes four polypeptides: Three initiate translation from non-AUG codons, Proc. Natl. Acad. Sci. 86:3978–3981.

    Article  PubMed  CAS  Google Scholar 

  24. Renko, ML, Quarto, N., Morimoto, T., and Rifkin, D.B., 1990, Nuclear and cytoplasmic localization of dif ferent fibroblast growth factor species. J. Cell. Physiol. 144:108–114.

    Article  PubMed  CAS  Google Scholar 

  25. Florkiewicz, R.Z., Baird, A., and Gonzalez, A.-M, 1991, Multiple forms of FGF-2: Differential nuclear and cell surface localization, Growth Factors 4:265–275.

    Article  PubMed  CAS  Google Scholar 

  26. Ishigooka, H., Aotaki-Keen, A.E., and L.M. Hjelmeland, 1992, Subcellular localization of bFGF in human retinal pigment epithelium in vitro, Exp. Eye Res. 55:203–214.

    Article  PubMed  CAS  Google Scholar 

  27. Florkiewicz, R.Z., Majack, R.A., Buechler, R.D., and E. Florkiewicz, 1995, Quantitative export of FGF-2 occurs through an alternative, energy-dependent, non-ER/Golgi pathway, J. Cell. Physiol. 162:388–399.

    Article  PubMed  CAS  Google Scholar 

  28. Li, L., and Turner, J.E., 1988, Inherited retinal dystrophy in the RCS rat: Prevention of photoreceptor de generation by pigment epithelial cell transplantation. Exp. Eye Res. 47:911–917.

    Article  PubMed  CAS  Google Scholar 

  29. Li, L., and Turner, J.E., 1991, Optimal conditions for the long-term photoreceptor cell rescue in RCS rats: The necessity for healthy RPE transplants. Exp. Eye Res. 52:669–679.

    Article  PubMed  CAS  Google Scholar 

  30. Hageman, G.S., Kirchoff-Rempe, M.A., Lewis, G.P., Fisher, S.K., and Anderson, D.H., Sequestration of basic fibroblast growth fac tor in the primate interphotoreceptor matrix. Proc. Natl. Acad. Sci. 88: 6706–6710.

    Google Scholar 

  31. McLaren, M.J., Hernandez, E., and Inana, G., 1994, Effect of intraocular injection of bFGF in RCS rat pups, Invest. Ophthalmol. Vis. Sci. 34(4):Suppl., 1498.

    Google Scholar 

  32. Klagsbrun, M., and Folkman, J., 1990, Angiogenesis, in: Peptide Growth Factors and Their Receptors, II (M.B. Sporn, and A.B. Roberts, eds.), pp. 549–586, Springer-Verlag, New York.

    Chapter  Google Scholar 

  33. Slavin, J., 1995, Fibroblast growth factors: at the heart of angiogenesis. Cell Biol Int. 19:431–444.

    Article  PubMed  CAS  Google Scholar 

  34. Soubrane, G., Cohen, S.Y., Delayre, T., Tassin, J., Hartmann, M.-P., Coscas, G.J., Courtois, Y., and Jeanny, J.-C, 1994, Basic fibroblast growth factor experimentally induced choroidal angiogenesis in the minipig. Curr. Eye Res. 13: 183–195.

    Article  PubMed  CAS  Google Scholar 

  35. Korte, G.E., Reppucci, V, and Henkind, P., 1984, RPE destruction causes choriocapillary atrophy, Invest. Ophthalmol. Vis. Sci. 25:1135–1145.

    PubMed  CAS  Google Scholar 

  36. Sakamoto, T., Sakamoto, H., Murphy, T.L., Spee, C., Soriano, D., Ishibashi, T., Hinton, D.R., and Ryan, S.J., 1995, Vessel formation by choroidal endothelial cells in vitro is modulated by retinal pigment epi thelial cells, Arch Ophthalmol. 113:512–520.

    Article  PubMed  CAS  Google Scholar 

  37. Chaitin, M.H., and Hall, M.O., 1983, Defective ingestion of rod outer segments by cultured dystrophic rat pigment epithelial cells, Invest. Ophthalmol. Vis. Sci. 24:812–820.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida, USA

    Margaret J. McLaren

Authors
  1. Margaret J. McLaren
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California, San Francisco, San Francisco, California, USA

    Matthew M. LaVail

  2. Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Joe G. Hollyfield

  3. University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

McLaren, M.J. (1997). Defective Choroidal Angiogenesis Precedes Retinal Pigment Epithelial Phagocytic Defect in Neonatal Rcs Rats. In: LaVail, M.M., Hollyfield, J.G., Anderson, R.E. (eds) Degenerative Retinal Diseases. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5933-7_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5933-7_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7718-4

  • Online ISBN: 978-1-4615-5933-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation