title: Gene expression profiling of the retina after transcorneal electrical stimulation in wild-type Brown Norway rats.
abstract: OBJECTIVE
  Transcorneal electrical stimulation (TES) has been beneficial in several neurodegenerative ocular diseases, but the exact mechanisms remain to be elucidated. This study was conducted to investigate the effects of TES on the retinas of wild-type Brown Norway (BN) rats by gene expression profiling and to assess its effects on retinal function and morphology.
  
  
  METHODS
  TES was applied to BN wild-type rat retinas in vivo for 1 hour (1-ms biphasic pulses at 20 Hz; 200 μA). RNA was isolated and processed for microarray-based profiling 4 hours after TES; differentially expressed genes from TES compared with those from sham-treated animals were validated by quantitative real-time polymerase chain reaction. Furthermore, the effect of TES was assessed at the structural and functional levels using electroretinography, confocal scanning laser ophthalmoscopy, optical coherence tomography, and immunohistochemistry.
  
  
  RESULTS
  Transcriptome changes associated with TES versus sham-stimulated BN wild-type retina were identified. Four hundred ninety genes were differentially expressed in TES and included potentially neuroprotective genes such as Bax or members of the tumor necrosis factor family (Tnfrsf11b, Tnrsf12a, Tnfsf13b, Tnfsf13). ERG recordings showed physiological retinal function after TES, and structural in vivo and ex vivo studies revealed intact retinal anatomy.
  
  
  CONCLUSIONS
  These results demonstrate that TES applied to the retina of the wild-type BN rats induces distinct transcriptome level changes and may help in the understanding of the mechanisms underlying TES. In addition, TES treatment indicates no negative effect on structure and function of the wild-type BN retina up to 35 hours after application.
authors.affiliation: University Eye Hospital and Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Willmann
authors.forename: Karin
authors.initials: K
authors.lastname: Schäferhoff
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Fischer
authors.forename: Blanca
authors.initials: B
authors.lastname: Arango-Gonzalez
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bolz
authors.forename: Lubka
authors.initials: L
authors.lastname: Naycheva
authors.forename: Tobias
authors.initials: T
authors.lastname: Röck
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Karl U
authors.initials: KU
authors.lastname: Bartz-Schmidt
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Andreas
authors.initials: A
authors.lastname: Schatz
authors.forename: Florian
authors.initials: F
authors.lastname: Gekeler
mesh_terms: D000818:Animals; D003315:Cornea / Q000502:physiology; D004558:Electric Stimulation; D004596:Electroretinography; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011914:Rats, Inbred BN; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism*; D041623:Tomography, Optical Coherence