Fibroblast growth factor receptor deficiency in dystrophic retinal pigmented epithelium

J Cell Physiol. 1993 Mar;154(3):631-42. doi: 10.1002/jcp.1041540323.

Abstract

The retinal pigmented epithelium (RPE) is known to be the site of the primary lesion in inherited retinal dystrophy in the Royal College of Surgeons (RCS) rat, a model for retinitis pigmentosa. Although the only functional defect so far detected in these cells is their failure to efficiently phagocytose shed photoreceptor outer segment debris, the actual cause of photoreceptor cell death is still unknown. Recently the possibility of "trophic factors" important in photoreceptor survival produced by normal RPE but not by dystrophic RPE has been suggested. Hence we decided to investigate the presence and abundance of two candidate diffusible factors, the acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), as well as their high affinity cell surface receptors (FGF-R). mRNA was isolated from primary cultures of purified normal and dystrophic RPE and analyzed by PCR amplification using specific oligonucleotide primers for aFGF and bFGF: the size and abundance of amplified fragments was similar for both cell types. Also, aFGF protein, detected by immunocytochemistry using specific antisera, appeared to be present in approximately equal amounts and distributed in a similar pattern. However, scatchard analysis of radio-labelled bFGF binding to primary cultures of normal and dystrophic rat RPE revealed that dystrophic RPE possess only 29% the number of surface receptors compared to congenic normal cells. Furthermore, the level of expression of FGF-R2 mRNA, but not that of FGF-R1, was significantly different. Other parameters measured (receptor affinity, profile of ligand internalization and degradation, receptor molecular weight and mitogenic activity) did not show any significant differences between normal and dystrophic RPE. The precise role of FGF-R deficiency in the etiology of the disease hence remains to be determined, but it indicates the importance of trophic factors in the normal functioning of the retina.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / chemistry
  • Cell Size
  • Cells, Cultured
  • Fibroblast Growth Factor 1 / analysis
  • Fibroblast Growth Factor 1 / metabolism
  • Fibroblast Growth Factor 1 / pharmacology
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Microscopy, Electron
  • Molecular Sequence Data
  • Molecular Weight
  • Oligodeoxyribonucleotides
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / pathology
  • Pigment Epithelium of Eye / ultrastructure
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Fibroblast Growth Factor / chemistry
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology

Substances

  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1