Retinal Expression of Fgf2 in RCS Rats with Subretinal Microphotodiode Array

PURPOSE. To test the hypothesis that subretinal electrical stimulation from a microphotodiode array (MPA) exerts a neuroprotective effect in Royal College of Surgeons (RCS) rats through the induction of growth factors. METHODS. At postnatal day 21, RCS rats were divided into four groups in which one eye per rat received treatment: (A) active MPA, (M) minimally active MPA, (S) sham surgery, or (C) no surgery and the opposite eye was unoperated. Dark-and light-adapted ERGs were recorded 1 week after surgery. A second set of A-, M-, and C-treated RCS rats had weekly ERG recordings for 4 weeks. Real-time RT-PCR was used to measure relative expression of mRNAs (Bdnf, Fgf2, Fgf1, Cntf, Gdnf, and Igf1) in retina samples collected 2 days after the final ERG. RESULTS. One week after surgery, there was a slight difference in dark-adapted ERG b-wave at the brightest flash intensity. Mean retinal Fgf2 expression in the treated eye relative to the opposite eye was greater for the A group (4.67 +/- 0.72) than for the M group (2.80 +/- 0.45; P = 0.0501), S group (2.03 +/- 0.45; P < 0.01), and C group (1.30 +/- 0.22; P < 0.001). No significant change was detected for Bdnf, Cntf, Fgf1, Gdnf, and Igf1. Four weeks after surgery, the A group had significantly larger dark-and light-adapted ERG b-waves than for the M and C groups (P = 0.01). Simultaneously, mean relative Fgf2 expression was again greater for the A group (3.28 +/- 0.61) than for the M (1.28 +/- 0.32; P < 0.05) and C (1.05 +/- 0.04; P < 0.05) groups. CONCLUSIONS. The results show subretinal implantation of an MPA induces selective expression of Fgf2 above that expected from a retina-piercing injury. Preservation of ERG b-wave amplitude 4 weeks after implantation is accompanied by elevated Fgf2 expression. These results suggest that Fgf2 may play a role in the neuroprotection provided by subretinal electrical stimulation. (Invest Ophthalmol Vis Sci. 2009; 50: 4523-4530) DOI:10.1167/iovs.08-2072