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V. T. Ciavatta, M. Kim, A. Faulkner, L. Bogdanowicz, J. R. Hetling, M. T. Pardue; Growth Factor Expression in Subretinal versus Corneal Electrical Stimulation in the RCS Rat Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2991. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Electrical stimulation from a subretinal microphotodiode delays loss of photoreceptor number and function in the dystrophic RCS rat and is accompanied by an increased expression of FGF-2. We hypothesized that functional preservation due to corneal electrical stimulation (Rhamani et al., ARVO 2007, Morimoto et al., IOVS 2007) would likewise be associated with an increased expression of FGF-2.
A controlled current source and 1 mm Ag/AgCl electrode contacting the cornea through a layer of saline were used for electrical stimulation. Animals were anesthetized with ketamine and xylazine and proparacaine was applied to both eyes. One eye of 21 day old RCS rats was subjected to 1.5, 4.0, and 15 microA/cm^2 (peak to peak, estimated current density at retina) of a sinusoidal current at 5 Hz for 30 minutes. Control animals received no current. Rats were sacrificed 24 hours after stimulation and whole retinas were dissected and processed to recover total RNA. Relative expression of FGF2 and IGF-1 in all retinas was assessed by real time PCR. To assess the effect of electrical stimulation on retinal growth factor expression, a growth factor expression ratio was calculated from relative expression in the treated eye divided by relative expression in the opposite eye.
Compared to no-current control animals (n = 3), expression ratio of IGF-1 in stimulated animals (n = 7) was 25% greater in the treated eye versus the fellow eye (p<0.05) and trended toward higher expression with higher current. Electrical stimulation had no effect on expression of FGF2.
Subretinal electrical stimulation delays photoreceptor cell and functional loss in the RCS rat and corneal electrical stimulation delays photoreceptor loss (RCS) and functional loss (RCS and P23H) in retinal degeneration (RD) models. Mechanistically, functional preservation in RCS is associated with an induction of a known neuroprotective growth factor, FGF2 and corneal electrical stimulation that spared retinal ganglion cells in rats following optic nerve transection was shown to induce IGF-1 in Muller cell endfeet. These observations along with the present results, which show an increased expression of IGF-1, but not of FGF2 in response to corneal electrical stimulation, suggest that subretinal and corneal electrical stimulation differ in neuroprotective mechanism in RD models.
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