Subretinal implantation of a microphotodiode array induces retinal expression of Fgf2 in RCS rats
Vincent T Ciavatta 1*,
Moon Kim 2,
Paul W. Wong 3,
John M. Nickerson 3,
R. Keith Shuler 3,
George Y. McLean 4,
and
Machelle T. Pardue 1
1 Rehabilitation Research and Development Center of Excellence, Atlanta VA Hospital, Decatur, Georgia, United States; Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
2 Rehabilitation Research and Development Center of Excellence, Atlanta VA Hospital, Decatur, Georgia, United States
3 Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
4 Optobionics, Inc., Palo Alto, California, United States
* To whom correspondence should be addressed. E-mail: vciavat{at}emory.edu.
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Abstract |
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Purpose. Test the hypothesis that subretinal electrical stimulation from a microphotodiode array (MPA) exerts a neuroprotective effect in RCS rats through the induction of growth factors.
Methods. RCS rats were divided into four groups at P21 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 one 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 greatest for the A group (4.67 +/-0.72) compared to 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 compared to the M and C groups (p<0.01). Simultaneously, mean relative Fgf2 expression was again greatest for the A group (3.28 +/-0.61) compared to the M (1.28 +/- 0.32, p<0.05) and C groups (1.05 +/-0.04, p<0.05).
Conclusion. 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.
Key Words:
growth factors, gene expression, electroretinography, electrical stimulation, microphotodiode array, neuroprotection
