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V. T. Ciavatta, M. K. Kim, Y. Cao, A. E. Faulkner, M. T. Pardue; Persistent Subretinal Electrical Stimulation Preserves Rod and Cone Function and Induces Prolonged Expression of Fgf2 in RCS Rats. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3228.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies showed preservation of photoreceptors and dark-adapted ERG response after 4 and 6 weeks of electrical stimulation from a subretinally-implanted microphotodiode array (MPA) (Pardue et al., IOVS 2005). Selective induction of Fgf2 after 1 week of MPA subretinal electrical stimulation has also been observed (Ciavatta et al., 2007 E-ARVO abstract 663). The present study examined the effects of MPA subretinal electrical stimulation on neuroprotection and growth factor expression in RCS rats at 4 weeks post-implantation.
At postnatal day 21 (P21), RCS rats were monocularly treated with a functional MPA (n=4), non-functional MPA (n=3), or no surgery (n=3). The functional MPA delivers ~500 µA/cm2 in response to the brightest ERG flash. ERGs, consisting of 10 dark-adapted steps (-3.4 to 2.1 log cd-s/m2) and 7 light-adapted steps (-0.82 to 1.88 log cd-s/m2), were recorded weekly for 4 weeks. Real-time RT-PCR was used to measure relative expression of Bdnf, Fgf2, Fgf1, Cntf, Gdnf, and Igf1 in retina samples collected 2 days after the final ERG.
Four weeks after surgery, the functional MPA treated eyes had 40% larger dark- and light-adapted ERG b-waves than the non-functional MPA treated eyes and the no surgery eyes (ANOVA, p < 0.01). Relative Fgf2 expression was greatest for the functional MPA implanted (3.28 +/-0.61) compared to the non-function (1.28 +/-0.32) and no surgery groups (1.05 +/-0.04) (ANOVA, p < 0.05, respectively). No significant expression changes were detected among the other growth factors.
Preservation of dark- and light-adapted ERG b-wave amplitude 4 weeks after functional MPA implantation suggests that subretinal electrical stimulation preserves rod and cone function in the RCS rat. The selective induction of the gene for FGF2 after 4 weeks of treatment suggests this growth factor is an important part of the subretinal electrical stimulation neuroprotective mechanism.
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