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Vincent T. Ciavatta, Moe H. Aung, Tracy S. Obertone, Jihyun K. You, Machelle T. Pardue; Subretinal Electrical Stimulation Preserves Visual Acuity In Dystrophic RCS Rats. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6415.
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© ARVO (1962-2015); The Authors (2016-present)
Subretinal electrical stimulation (SES) from a microphotodiode array (MPA) temporarily preserves retinal function and local morphology (Pardue et al., PMID:15671299) and is associated with upregulated retinal FGF2 expression (Ciavatta et al., PMID:19264883), particularly in Müller glia (You et al., 2011 E-ARVO abstract #1865) in dystrophic RCS rats. These studies determined how low level SES affects visual function in dystrophic RCS rats as assessed by optokinetic tracking reflex (OKT) and if blocking FGF2 receptor, FGFR1, would eliminate the neuroprotective effects.
At postnatal day 21 (P21), RCS rats were subretinally implanted in one eye with a MPA (n=28), or nominally active device (NA) (n=10). Beginning 7 days after surgery and weekly thereafter for 4 weeks, rats were dark-adapted, anesthetized, and flashed with LED and xenon sources using increasing flash stimuli from Ganzfeld dome to produce short duration (<1 ms), low intensity (~1 nA/cm2 to 100 μA/cm2) pulses from the MPA. A subset of MPA-implanted eyes received 1 μL intravitreal injections of FGFR1 inhibitor, PD173074 at 250 nM (n=9), or PBS (n=8) immediately after flash stimulation. OKT was assessed weekly, 3 days prior to flash stimulation. Normalized visual acuity was computed for each rat as: (implanted eye threshold - opposite eye threshold). Rats were sacrificed at P51. Western blots for FGF2 were performed on a subset of rats without intraocular injections (MPA, n=3; NA, n=4).
Four weeks after surgery, normalized visual acuity was higher in MPA-implanted eyes compared to NA-implanted eyes (p<0.05,t-test). Visual acuity in MPA+PD173074-treated eyes was indistinguishable from opposite eyes, whereas MPA+vehicle-treated eyes tended to maintain higher visual acuity than opposite eyes. From western analysis, FGF2 tended to be higher in MPA-implanted eyes compared to NA-implanted eyes.
In the 4 week study, low level SES preserved visual function in dystrophic RCS rats. FGFR1 inhibition appears to eliminate some of this effect, suggesting that FGF2 upregulation and signal transduction is likely integral to the neuroprotective effects from SES.
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