Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix.

Abstract

The interphotoreceptor matrix (IPM) occupies the extracellular space between the photoreceptors of the retina and the apical surface of the retinal pigmented epithelium. A large proportion of the IPM is composed of aqueousinsoluble glycoconjugates, including chondroitin sulfatecontaining proteoglycans, the distribution of which exhibits both apical-basal and photoreceptor cell type-specific heterogeneities. The precise function of most insoluble IPM constituents is unknown, although the available evidence suggests some may contribute to retinal adhesion or photoreceptor survival. We have now identified basic fibroblast growth factor (bFGF), or an immunologically related protein from the FGF family, within the IPM. The IPM is labeled on sections of primate retinas by a battery of polyclonal antibodies (Abs) directed against various peptide sequences of bFGF and by an Ab to bovine brain bFGF. bFGF Abs also bind to purified preparations of aqueous-insoluble IPM. AU bFGF Abs utilized cross-react with equivalent low molecular mass components of 16.5-17.5 kDa on Western blots of insoluble IPM proteins, purified bFGF, and recombinant bFGF. The Abs do not bind any aqueous-soluble IPM components, suggesting that the bFGF is normally bound to an insoluble 1PM constituent(s) in situ. The fact that bFGF is sequestered in the IPM and is located in such close proximity to the photoreceptors, the retinal pigmented epithelium, and Mueller's glia raises the strong possibility that it is synthesized by and regulates the activities of one or more of these three cell types in vivo.The fibroblast growth factors (FGFs) are a family of peptides that have been isolated from a broad range of cell types. FGFs share a number of structural, biochemical, and biological properties, the most characteristic being that they bind to heparin (1-4). The FGF family consists of acidic FGF (aFGF), basic FGF (bFGF), and a number of other related molecules that exhibit significant sequence homology to these two proteins. FGFs, like some other growth factors, are regarded as multifunctional in that they have a range of effects and activities in vitro that depend upon the target cell type (5). To date, FGFs have been shown: to influence neuronal differentiation, survival, and regeneration (6-9); to act as mitogens (10-13) and as inducing factors (14-17); to modulate protein synthesis (12,18); and to induce cell motility and migration (19). Much more is known about the effects of FGFs in vitro than under in vivo conditions.Although biochemical assays have shown that FGFs are present in a wide variety of cell types and tissues (for review, see refs. 3 and 4), only a few studies have sought to determine their specific cellular and/or extracellular distributions. Antibodies (Abs) have been used to localize bFGF to the cytoplasm of rat brain neurons (20-22) and chicken striated muscle myoblasts (23) and to the extracellular matrix of mouse hind-limb muscle (24). A recent comprehensive study of bFGF distribution in the 18-day rat fetus revealed intrace...

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“…FGF2 is associated with endothelial ECM in vitro 15,16) and basement membranes in vivo 17,18,19) . ECM may act as a physiological reservoir for extracellular FGF2.…”

“…Accordingly, FGF2 is associated with endothelial ECM in vitro 15,16) and basement membranes in vivo [17][18][19] . Newly synthesized FGF2 is stored in the ECM from where it is released to induce long-term stimulation of target cells 15,20) .…”

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“…The precise function of most insoluble IPM constituents is unknown although the available evidence suggests that some of them may contribute to retinal adhesion or photoreceptor survival. It is also a reservoir of growth factors such as basic fibroblastic growth factor 26 or pigment epithelium-derived factor 27 which are embedded inside the structure.…”

Army Science Conference Proceedings Held in Orlando, Florida on June 22 - 25, 1992. Volume 3, Principal Authors N Through Z.

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