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F.–Q. Liang, M. Klein, K. Locke, B.F. Godley, D.G. Birch; The Inhibitory Effect of CNTF on Retinal Function: Mediation by bFGF . Invest. Ophthalmol. Vis. Sci. 2006;47(13):840.
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© ARVO (1962-2015); The Authors (2016-present)
Ciliary neurotrophic factor (CNTF) provides effective photoreceptor protection morphologically, but may decrease the ERG, in animal models of retinitis pigmentosa (RP). The underlying mechanisms that account for the paradoxical decrease in ERG by CNTF are not known. Interestingly, it has been shown that CNTF can induce production and release of basic fibroblast growth factor (bFGF) from glial cells, and bFGF is able to attenuate ERG responses through inhibition of synaptic transmission in normal animals (Gargini et al 1999). Hence, we hypothesize that CNTF inhibition of ERG function may be mediated by bFGF. As the first step toward testing this hypothesis, we examined whether a lack of bFGF expression can prevent or reduce CNTF–induced ERG reduction by using the bFGF knockout (bFGF–/–) mice.
AAV.CMV.CNTF was made to express a secretable CNTF in tandem with a marker GFP. The bFGF–/– (n=10) and wild–type (n=5) mice were intravitreally injected with AAV.CNTF (4x10e9 GC) in one eye and AAV.EGFP (4.8 x 10e9) or sham injection in the fellow eye at age of 1 month. Full–field ERGs were performed at 4–5 weeks post–injection. Retinal structures and transduced retinal cells were examined by bright and fluorescent microscopy. CNTF and bFGF levels in the retinas were measured by ELISA and Western blot assay, respectively.
Rod and cone ERG amplitudes in the AAV.CNTF injected eyes were significantly reduced in both bFGF–/– and wild–type mice, relative to control eyes. However, peak–to–peak amplitudes in CNTF–treated eyes were significantly larger in bFGF–/– mice than in wild–type mice (116.1±;65.1 vs 14.6±;9.4 uV, p <0.01), suggesting a lack of bFGF expression ameliorates CNTF–induced ERG reduction. Histological examination showed AAV–CNTF primarily transduced cells in the inner retina and no obvious photoreceptor loss in either bFGF–/– or wild–type mice following AAV–CNTF injection. In both types of animals,CNTF levels were significantly increased in AAV–CNTF–injected eyes compared to the control eyes (314±;75.4 vs 85.3±;22 pg/mg protein. In the wild–type animals, bFGF levels were approximately 2 fold higher in AAV–CNTF injected eyes than fellow control eyes.
The data support a role of bFGF in mediating the inhibitory effect of CNTF on retinal function.
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