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J.M. Provis, A.E. Hendrickson, R.C. Natoli, E.E. G. Cornish; A Role for Fibroblast Growth Factors (FGFs) in Morphological Specialization of the Primate Foveal Cone Mosaic? . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5305.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the hypothesis that gradients of FGF ligands and receptors may correlate with gradients of cone elongation and differentiation present in the developing macaque retina.Methods: Macaque retinae aged between foetal day (Fd) 65 and 2.5 years postnatal (P2.5y) were fixed in Methyl Carnoy's, embedded in paraffin and sectioned parallel to the horizontal meridian. DIG–labeled RNA probes were prepared from rat FGF–2, FGF receptor 1 (R1) (flg) and R2 (bek) cDNAs (>88% homology with human) for in situ hybridisation. Sequenced DNA fragments from fetal human retina were used to generate RNA probes for FGFR3, FGFR4 and FGFrl1. Labeled RNA was detected using the fluorescent marker ‘Fast Red’ (Roche) and levels of mRNA expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy and optical densitometry. Antibodies to FGFR were used to demonstrate distribution of FGFR proteins. Results: At Fd90 cones near the optic disc have markedly elongated axons compared to cones closer to or within the foveal cone mosaic. This marks the beginning of a wave of cone differentiation that spreads towards the central region over the remainder of fetal life. By Fd130 cones within the foveal cone mosaic have differentiated inner and outer segments, but cuboidal somas and stunted axonal processes are a morphological mark of immaturity; in contrast, cones on the foveal rim have well developed inner and outer segments and elongated axons oriented away from the fovea, resembling the fibres of Henle. By birth foveal cones are narrower, elongated, and more densely packed than cones on the foveal rim and have well developed fibres of Henle, more closely resembling adult retina. Patterns of mRNA expression reveal low levels of FGF2 and FGFR4 mRNAs expressed by ‘stunted’ foveal cones between Fd95 and Fd164, compared with more elongated cones on the foveal rim and near the optic disc. Conclusion. FGF signalling may have a role in the narrowing and elongation of cones, associated with the establishment of the high–density foveal cone mosaic.
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