title: Effects of subretinal electrical stimulation in mer-KO mice.
abstract: OBJECTIVE
  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 σ, 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.
authors.affiliation: Rehabilitation Research and Development Service, Atlanta Department of Veterans Affairs, Decatur, Georgia 30033, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mocko
authors.forename: Moon
authors.initials: M
authors.lastname: Kim
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Faulkner
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ciavatta
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D000818:Animals; D002452:Cell Count; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D003623:Dark Adaptation; D004558:Electric Stimulation / Q000379:methods*; D004596:Electroretinography; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D012160:Retina / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D015854:Up-Regulation; D000076202:c-Mer Tyrosine Kinase
chemical_list: D020934:Ciliary Neurotrophic Factor; D011518:Proto-Oncogene Proteins; D016222:Fibroblast Growth Factor 2; C490767:Mertk protein, mouse; C490765:Mertk protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase