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G. Willmann, K. Schäferhoff, A. Schatz, M. Bonin, H. Enderle, K. U. Bartz-Schmidt, E. Zrenner, F. Gekeler; Gene Expression Profiling of the Retina After Transcorneal Electrical Stimulation in Wildtype Brown Norway Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3713.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of transcorneal electrical stimulation (TES) on the retina of wildtype Brown Norway (BN) rats by gene expression profiling.
TES was applied to 56 BN rats in vivo for 1h (1ms biphasic pulses at 20Hz; current: 200 µA). Prior to microarray studies, known TES regulated neurotrophic factors (i.e. IGF1, Bcl2, CNTF, Fgf2 and BDNF) were studied at the mRNA level by quantitative real-time polymerase chain reaction (qPCR) at 0h, 4h, 10h, 24h, 2d, 4d and 7d post TES to determine optimal time points. Gene expression profiling was analyzed 0, 4, and 24 hours after TES. Major transcriptome-level changes were independently validated at the mRNA level by qPCR. Electroretinograms (ERGs) were recorded for functional analysis at the respective time points.
qPCR analysis of selected neurotrophic factors revealed overall highest fold level changes at 4h and 10h after TES. 20 BN rats were then analyzed by gene expression profiling. In total 163 genes were differentially expressed with a p-value <0.05 and a 1.5 fold cutoff at 4h versus 24h after TES. These results demonstrate the direct effect of TES on the retina of wildtype BN rats and showed differential expression of several transcription factors that may play a crucial role in neuroprotection of the retina. Functional analysis by ERGs at the respective time points showed normal ERG recordings.
TES applied to the retina of wildtype BN rats induces a variety of transcriptome level changes. Our study may help to understand the mechanisms underlying TES induced neuroprotection and may contribute to define more clearly therapeutic options for patients with neurodegenerative retinal diseases.
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