Retinal expression of Fgf2 in RCS rats with subretinal microphotodiode array.
OBJECTIVE
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.
Ciavatta
Vincent T
VT
Rehab R&D Center, Atlanta VA Medical Center, Decatur, Georgia, USA. vciavat@emory.edu
Kim
Moon
M
Wong
Paul
P
Nickerson
John M
JM
Shuler
R Keith
RK
McLean
George Y
GY
Pardue
Machelle T
MT
D000818:Animals; D000831:Animals, Newborn; D003623:Dark Adaptation; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D004596:Electroretinography; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D008839:Microelectrodes; D019736:Prostheses and Implants; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011922:Rats, Mutant Strains; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012666:Semiconductors
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2