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Publication : Effects of subretinal electrical stimulation in mer-KO mice.

First Author  Mocko JA Year  2011
Journal  Invest Ophthalmol Vis Sci Volume  52
Issue  7 Pages  4223-30
PubMed ID  21467171 Mgi Jnum  J:181427
Mgi Id  MGI:5311300 Doi  10.1167/iovs.10-6750
Citation  Mocko JA, et al. (2011) Effects of subretinal electrical stimulation in mer-KO mice. Invest Ophthalmol Vis Sci 52(7):4223-30
abstractText  PURPOSE: Subretinal electrical stimulation (SES) from microphotodiode arrays protects photoreceptors in the RCS rat model of retinitis pigmentosa. The authors examined whether mer(kd) mice, which share a Mertk mutation with RCS rats, showed similar neuroprotective effects from SES. METHODS: Mer(kd) mice were implanted with a microphotodiode array at postnatal day (P) 14. Weekly electroretinograms (ERGs) followed by retinal histology at week 4 were compared with those of age-matched controls. RT-PCR for fibroblast growth factor beta (Fgf2), ciliary nerve trophic factor (Cntf), glial-derived neurotrophic factor (Gdnf), insulin growth factor 1 (Igf1), and glial fibrillary acidic protein (Gfap) was performed on retinas at 1 week after surgery. Rates of degeneration using ERG parameters were compared between mer(kd) mice and RCS rats from P28 to P42. RESULTS: SES-treated mer(kd) mice showed no differences in ERG a- and b-wave amplitudes or photoreceptor numbers compared with controls. However, the expression of Fgf2 and Cntf was greater (6.5 +/- 1.9- and 2.5 +/- 0.5-fold, respectively; P < 0.02) in SES-treated mer(kd) retinas. Rates of degeneration were faster for dark-adapted maximal b-wave, log sigma, and oscillatory potentials in mer(kd) mice than in RCS rats. CONCLUSIONS: Although SES upregulated Fgf2 in mer(kd) retinas, as reported previously for RCS retinas, this was not accompanied by neuroprotection of photoreceptors. Comparisons of ERG responses from mer(kd) mice and RCS rats across different ages showed inner retinal dysfunction in mer(kd) mice but not in RCS rats. This inner retinal dysfunction and the faster rate of degeneration in mer(kd) mice may produce a retinal environment that is not responsive to neuroprotection from SES.
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