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PMID: 18172115 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Chronic intravitreous infusion of ciliary neurotrophic factor modulates electrical retinal stimulation thresholds in the RCS rat.

Investigative ophthalmology & visual science ·Vol. 49 ·No. 1 ·2008-01-00 ·Pages 372-9

Kent TL, Glybina IV, Abrams GW, Iezzi R

Abstract

To determine whether the sustained intravitreous delivery of CNTF modulates cortical response thresholds to electrical retinal stimulation in the RCS rat model of retinal degeneration. Animals were assigned to four groups: untreated, nonsurgical control and infusion groups of 10 ng/d CNTF, 1 ng/d CNTF, and PBS vehicle control. Thresholds for electrically evoked cortical potentials (EECPs) were recorded in response to transcorneal electrical stimulation of the retina at p30 and again at p60, after a three-week infusion. As the retina degenerated over time, EECP thresholds in response to electrical retinal stimulation increased. Eyes treated with 10 ng/d CNTF demonstrated significantly greater retinal sensitivity to electrical stimulation when compared with all other groups. In addition, eyes treated with 1 ng/d CNTF demonstrated significantly greater retinal sensitivity than both PBS-treated and untreated control groups. Retinal sensitivity to electrical stimulation was preserved in animals treated with chronic intravitreous infusion of CNTF. These data suggest that CNTF-mediated retinal neuroprotection may be a novel therapy that can lower stimulus thresholds in patients about to undergo retinal prosthesis implantation. Furthermore, it may maintain the long-term efficacy of these devices in patients.

MeSH Terms
Animals Ciliary Neurotrophic Factor/administration & dosage Electric Stimulation Evoked Potentials, Somatosensory/drug effects Infusions, Parenteral Rats Rats, Mutant Strains Retina/physiology Retinitis Pigmentosa/physiopathology Sensory Thresholds/drug effects Vitreous Body
Chemicals
Ciliary Neurotrophic Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kent Tiffany L
Department of Ophthalmology, Kresge Eye Institute, Ligon Research Center of Vision, Wayne State University, 4717 St. Antoine, Detroit, MI 47201, USA.
Glybina Inna V
Abrams Gary W
Iezzi Raymond
References (42)
42 references, click to expand
  1. Visual perception elicited by electrical stimulation of retina in blind humans.
    Arch Ophthalmol. 1996 Jan;114(1):40-6 PMID: 8540849
  2. Can potentials from the visual cortex be elicited electrically despite severe retinal degeneration and a markedly reduced electroretinogram?
    Ger J Ophthalmol. 1995 Jan;4(1):57-64 PMID: 7728112
  3. Pattern electrical stimulation of the human retina.
    Vision Res. 1999 Jul;39(15):2569-76 PMID: 10396625
  4. Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse.
    Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2724-34 PMID: 10509671
  5. Neuroprotective effect of subretinal implants in the RCS rat.
    Invest Ophthalmol Vis Sci. 2005 Feb;46(2):674-82 PMID: 15671299
  6. CNTF and BDNF have similar effects on retinal ganglion cell survival but differential effects on nitric oxide synthase expression soon after optic nerve injury.
    Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1497-503 PMID: 15790921
  7. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.
    Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2147-55 PMID: 15914636
  8. CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina.
    Exp Eye Res. 2006 Mar;82(3):395-404 PMID: 16143329
  9. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants.
    Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3896-901 PMID: 16505355
  10. Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa.
    Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1389-400 PMID: 17325188
  11. Neuroprotection in the juvenile rat model of light-induced retinopathy: evidence suggesting a role for FGF-2 and CNTF.
    Invest Ophthalmol Vis Sci. 2007 May;48(5):2311-20 PMID: 17460296
  12. Neuroprotective effect of transcorneal electrical stimulation on the acute phase of optic nerve injury.
    Invest Ophthalmol Vis Sci. 2007 May;48(5):2356-61 PMID: 17460302
  13. Neurotrophic factors cause activation of intracellular signaling pathways in Müller cells and other cells of the inner retina, but not photoreceptors.
    Invest Ophthalmol Vis Sci. 2000 Mar;41(3):927-36 PMID: 10711715
  14. Chronaxie calculated from current-duration and voltage-duration data.
    J Neurosci Methods. 2000 Apr 1;97(1):45-50 PMID: 10771074
  15. Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia.
    J Neurosci. 2000 Jun 1;20(11):4081-90 PMID: 10818143
  16. Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa.
    Mol Ther. 2001 Nov;4(5):461-72 PMID: 11708883
  17. Neurotrophic factor intervention restores auditory function in deafened animals.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1657-60 PMID: 11818566
  18. Thrombopoietin regulates Bcl-xL gene expression through Stat5 and phosphatidylinositol 3-kinase activation pathways.
    J Biol Chem. 2002 Mar 8;277(10):8329-37 PMID: 11756417
  19. Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation.
    Exp Eye Res. 2002 Jun;74(6):719-35 PMID: 12126945
  20. Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa.
    Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3292-8 PMID: 12356837
  21. Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration.
    J Neurosci. 2002 Nov 1;22(21):9228-36 PMID: 12417648
  22. Retinal neuroprotection by growth factors: a mechanistic perspective.
    J Cell Biochem. 2003 Jan 1;88(1):57-75 PMID: 12461775
  23. Intraocular gene delivery of ciliary neurotrophic factor results in significant loss of retinal function in normal mice and in the Prph2Rd2/Rd2 model of retinal degeneration.
    Gene Ther. 2003 Mar;10(6):523-7 PMID: 12621456
  24. Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats.
    Gene Ther. 2003 Aug;10(17):1503-11 PMID: 12900766
  25. Location of CNTFRalpha on outer segments: evidence of the site of action of CNTF in rat retina.
    Brain Res. 2003 Sep 26;985(2):169-75 PMID: 12967721
  26. Retinal remodeling in inherited photoreceptor degenerations.
    Mol Neurobiol. 2003 Oct;28(2):139-47 PMID: 14576452
  27. Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays.
    Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5355-61 PMID: 14638738
  28. Accuracy limitations of chronaxie values.
    IEEE Trans Biomed Eng. 2004 Jan;51(1):176-81 PMID: 14723507
  29. Comparison of electrical stimulation thresholds in normal and retinal degenerated mouse retina.
    Jpn J Ophthalmol. 2004 Jul-Aug;48(4):345-9 PMID: 15295659
  30. Fast and slow artificial diurnal rhythms (light-darkness-light) and the rate of progression of retinal degeneration in dystrophic RCS rats. An electroretinographic study.
    Br J Ophthalmol. 1985 Jun;69(6):468-70 PMID: 4039947
  31. Retinitis pigmentosa.
    Surv Ophthalmol. 1988 Nov-Dec;33(3):137-77 PMID: 3068820
  32. Photoreceptor rescue in the RCS rat without pigment epithelium transplantation.
    Curr Eye Res. 1990 Feb;9(2):183-91 PMID: 2335114
  33. Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor.
    Nature. 1990 Sep 6;347(6288):83-6 PMID: 2168521
  34. Effects of macrophage and retinal pigment epithelial cell transplants on photoreceptor cell rescue in RCS rats.
    Curr Eye Res. 1991 Oct;10(10):947-58 PMID: 1959383
  35. Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa.
    Arch Ophthalmol. 1992 Nov;110(11):1634-9 PMID: 1444925
  36. Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11249-53 PMID: 1454803
  37. Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats.
    J Neurobiol. 1993 Jan;24(1):23-36 PMID: 8419522
  38. Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo.
    Brain Res. 1993 Feb 5;602(2):304-17 PMID: 8448673
  39. Retinitis pigmentosa. The Friedenwald Lecture.
    Invest Ophthalmol Vis Sci. 1993 Apr;34(5):1659-76 PMID: 8473105
  40. Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus.
    Science. 1993 Dec 3;262(5139):1575-9 PMID: 7504325
  41. Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats.
    J Neurosci. 1994 Jul;14(7):4368-74 PMID: 8027784
  42. Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse.
    J Neurosci. 1998 Nov 15;18(22):9282-93 PMID: 9801367
Article Info
Journal
Investigative ophthalmology & visual science
Abbr.
Invest Ophthalmol Vis Sci
ISSN
0146-0404
DOI
10.1167/iovs.07-0952
Published
2008-01-00
Pages
372-9
Language
English
Region
United States
NLM ID
7703701
PMCID
PMC2486405
Subset
IM
Grants
NEI NIH HHS · L30 EY016016-01 · United States
NEI NIH HHS · L30 EY016016-02 · United States
NEI NIH HHS · L30 EY016016-03 · United States
NEI NIH HHS · R21 EY018709-01 · United States
External Links
PubMed source DOI: 10.1167/iovs.07-0952 PMC Full Text View journal details
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