[FGF and physiopathological implications].
The role of FGF in retinal pathologies can be considered in two respects: 1-as a causative agent (for instance, stimulating aberrant growth or abnormally affecting some aspects of cellular behaviour), or 2-as a possible therapeutic drug (for instance, its ability to rescue neuronal cells from programmed or surgically-induced death), there is evidence for both: the retina, particularly the photoreceptors (PR), seems to be highly succeptible to a host of genetic defects, for instance, in the rat mutant RCS a defect in the pigmented epithelial cells (RPE) leads to the destruction of the PR. Transocular injection of FGF into RCS rats reduces the rate of PR cell loss. On the other hand, we have recently identify a difference in FGF-Receptor cell biology in the RCS mutant which may underline this particular dystrophy. Cultures of purified RPE cells were established from the dystrophic RCS rat and its congenic normal sighted control, and the number and affinity of cell surface FGF-R determined by incubation with 125I-bFGF. Scatchard analysis of the bining data indicated that whereas affinites were in both strains around 60pM, there was a large reduction in receptor number, about 70% in the mutant. Analysis of other FGF/FGF-R criteria, such as mitogenic activity, receptor molecular weight and the profile of FGF degradatoin showed no significant differences between the strains. Thus, defects in the FGF/FGF-R regulating system may actually led to retinal degeneration (RCS rat). But, once again, the underlying principles of FGF mechanisms of action in vivo are at present too incompletely understood to permit rationalization of these various observations.
Mascarelli
F
F
Unité de Rercherches Gérontologiques, INSERM U118, Paris.
Torriglia
A
A
Soubrane
G
G
Hicks
D
D
Malecaze
F
F
Courtois
Y
Y
D000818:Animals; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006801:Humans; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology*; D015861:Retinal Neovascularization / Q000503:physiopathology*
D011956:Receptors, Cell Surface; D005346:Fibroblast Growth Factors
FGFs et implications physiopathologiques.