On the Role of CNTF as a Pontential Therapy for Retinal Degeneration: Dr. Jekyll or Mr. Hyde?

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

Among the various neuroprotective agents, ciliary neurotrophic factor (CNTF) has been themost tested compound in animal models of retinal degeneration. CNTF was initially isolated from the chick eye as a soluble factor that promotes the survival of dissociated ciliary ganglionic neurons of 12-day chick embryos (Adler et al., 1979). Its use as a neuroprotective agent for the retina was first tested in rats 15 years ago in a light-damage model of retinal degeneration (LaVail et al., 1992). Since then, numerous studies conducted in a variety of animal models have demonstrated CNTF’s pro-survival effect on photoreceptor cells.


Retinitis Pigmentosa Photoreceptor Cell Retinal Degeneration Ciliary Neurotrophic Factor Photoreceptor Degeneration 
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  1. Adler, R., Landa, K.B., Manthorpe, M., Varon, S., 1979. Cholinergic neuronotrophic factors: intraocular distribution of trophic activity for ciliary neurons. Science. 204: 1434–1436.PubMedCrossRefGoogle Scholar
  2. Beltran, W.A., Hammond, P., Acland, G.M., Aguirre, G.D., 2006. A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci. 47: 1669–1681.PubMedCrossRefGoogle Scholar
  3. Beltran, W.A., Rohrer, H., Aguirre, G.D., 2005. Immunolocalization of ciliary neurotrophic factor receptor alpha (CNTFRα in mammalian photoreceptor cells. Mol Vis. 11: 232–244.PubMedGoogle Scholar
  4. Beltran, W.A., Wen, R., Acland, G.M., Aguirre, G.D., 2007. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina. Exp Eye Res. 148: 53–64.Google Scholar
  5. Beltran, W.A., Zhang, Q., Kijas, J.W., Gu, D., et al., 2003. Cloning, mapping, and retinal expression of the canine ciliary neurotrophic factor receptor alpha (CNTFRα. Invest Ophthalmol Vis Sci. 44: 3642–3649PubMedCrossRefGoogle Scholar
  6. Bok, D., Yasumura, D., Matthes, M.T., Ruiz, et al., 2002. Effects of AAV-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation. Exp Eye Res. 74: 719–735.PubMedCrossRefGoogle Scholar
  7. Bush, R.A., Lei, B., Tao, W., Raz, D., et al., 2004. Encapsulated cell-based intraocular delivery of CNTF in normal rabbit: dose-dependent effects on ERG and retinal histology. Invest Ophthalmol Vis Sci. 45: 2420–2430.PubMedCrossRefGoogle Scholar
  8. Cayouette, M., Behn, D., Sendtner, M., Lachapelle, P., et al., 1998. Intraocular gene transfer of CNTF prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse. J Neurosci. 18: 9282–9293.PubMedGoogle Scholar
  9. Cayouette, M., Gravel, C., 1997. Adenovirus-mediated gene transfer of ciliary neurotrophic factor can prevent photoreceptor degeneration in the retinal degeneration (rd) mouse. Hum Gene Ther. 8: 423–430.PubMedCrossRefGoogle Scholar
  10. Chong, N.H., Alexander, R.A., Waters, L., Barnett, K.C., et al., 1999. Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration. Invest Ophthalmol Vis Sci. 40: 1298–1305.PubMedGoogle Scholar
  11. Harada, T., Harada, C., Kohsaka, S., Wada, E., et al., 2002. Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. J Neurosci. 22: 9228–9236.PubMedGoogle Scholar
  12. Huang, S.P., Lin, P.K., Liu, J.H., Khor, C.N., et al., 2004. Intraocular gene transfer of ciliary neurotrophic factor rescues photoreceptor degeneration in RCS rats. J Biomed Sci. 11: 37–48.PubMedCrossRefGoogle Scholar
  13. Ju, W.K., Lee, M.Y., Hofmann, H.D., Kirsch, M., et al., 2000. Increased expression of ciliary neurotrophic factor receptor alpha mRNA in the ischemic rat retina. Neurosci Lett. 283: 133–136.PubMedCrossRefGoogle Scholar
  14. LaVail, M.M., Unoki, K., Yasumura, D., Matthes, M.T., et al., 1992. Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci USA. 89: 11249–11253.PubMedCrossRefGoogle Scholar
  15. LaVail, M.M., Yasumura, D., Matthes, M.T., Lau-Villacorta, C., et al., 1998. Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci. 39: 592–602.PubMedGoogle Scholar
  16. Liang, F.Q., Aleman, T.S., Dejneka, N.S., Dudus, et al., 2001a. Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa. Mol Ther. 4: 461–472.Google Scholar
  17. Liang, F.Q., Dejneka, N.S., Cohen, D.R., Krasnoperova, N.V., et al., 2001b. AAV-mediated delivery of CNTF prolongs photoreceptor survival in the rhodopsin knockout mouse. Mol Ther. 3: 241–248.Google Scholar
  18. Peterson, W.M., Wang, Q., Tzekova, R.,Wiegand, S.J., 2000. Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia. J Neurosci. 20: 4081–4090.PubMedGoogle Scholar
  19. Rhee, K.D.,Yang, X.J., 2003. Expression of cytokine signal transduction components in the postnatal mouse retina. Mol Vis. 9: 715–722.PubMedGoogle Scholar
  20. Schlichtenbrede, F.C., MacNeil, A., Bainbridge, J.W., Tschernutter, M., et al., 2003. 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. 10: 523–527.PubMedCrossRefGoogle Scholar
  21. Sieving, P.A., Caruso, R.C., Tao, W., Coleman, H.R., et al., 2006. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proc Natl Acad Sci USA. 103: 3896–3901.PubMedCrossRefGoogle Scholar
  22. Tao, W., Wen, R., Goddard, M.B., Sherman, S.D., O’Rourke, P.J., et al., 2002. Encapsulated cell based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 43: 3292–3298.PubMedGoogle Scholar
  23. Wahlin, K.J., Campochiaro, P.A., Zack, D.J., Adler, R., 2000. Neurotrophic factors cause activation of intracellular signaling pathways in Muller cells and other cells of the inner retina, but not photoreceptors. Invest Ophthalmol Vis Sci. 41: 927–936.PubMedGoogle Scholar
  24. Wahlin, K.J., Lim, L., Grice, E.A., Campochiaro, P.A., et al., 2004. A method for analysis of gene expression in isolated mouse photoreceptor and Muller cells. Mol Vis. 10: 366–375.PubMedGoogle Scholar
  25. Wen, R., Song, Y., Kjellstrom, S., Tanikawa, A., et al., 2006. Regulation of rod phototransduction machinery by ciliary neurotrophic factor. J Neurosci. 26: 13523–13530.PubMedCrossRefGoogle Scholar
  26. Zeiss, C.J., Allore, H.G., Towle, V., Tao, W., 2006. CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina. Exp Eye Res. 82: 395–404.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Section of Ophthalmology, Department of Clinical StudiesSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaUSA

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