Abstract
Secondary cone degeneration in the transgenic rats carrying the S334ter rhodopsin mutation (S334ter-3 rats) starts at the peak of rod degeneration (PD12) and progresses with age. An early sign of cone degeneration is the loss of cone outer segments (COS) distributed in many small patches throughout the retina. Cone cell death occurs about 2 months later. When treated with CNTF (ciliary neurotrophic factor), impaired cones regenerate COS. Sustained delivery of CNTF prevents cones from degeneration and helps to maintain COS and function. These results indicate that cone degeneration is reversible at early stages and support a therapeutic strategy of sustained delivery of CNTF to prevent cone degeneration.
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Bok D, Yasumura D, Matthes MT et al (2002) 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 74:719–735
Caffe AR, Soderpalm AK, Holmqvist I et al (2001) A combination of CNTF and BDNF rescues rd photoreceptors but changes rod differentiation in the presence of RPE in retinal explants. Invest Ophthalmol Vis Sci 42:275–282
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
Cayouette M, Behn D, Sendtner M et al (1998) Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse. J Neurosci 18:9282–9293
Chong NH, Alexander RA, Waters L 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
Delyfer MN, Leveillard T, Mohand-Said S et al (2004) Inherited retinal degenerations: therapeutic prospects. Biol Cell 96:261–269
Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809
LaVail MM, Unoki K, Yasumura D et al (1992) Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci U S A 89:11249–11253
LaVail MM, Yasumura D, Matthes MT et al (1998) Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci 39:592–602
Li Y, Tao W, Luo L et al (2010) CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. PLoS One 5:e9495
Liang FQ, Aleman TS, Dejneka NS et al (2001) Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa. Mol Ther 4:461–472
Liu C, Li Y, Peng M et al (1999) Activation of caspase-3 in the retina of transgenic rats with the rhodopsin mutation s334ter during photoreceptor degeneration. J Neurosci 19:4778–4785
Sieving PA, Caruso RC, Tao W 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 U S A 103:3896–3901
Talcott K, E., Ratnam K, Sundquist SM et al (2010) Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest Ophthalmol Vis Sci (in press)
Tao W (2006) Application of encapsulated cell technology for retinal degenerative diseases. Expert Opin Biol Ther 6:717–726
Tao W, Wen R (2007) Application of encapsulated eell technology for retinal degenerative diseases. In: Tombran-Tink J, Barnstable CJ (eds) Retinal Degenerations. Humana Press
Tao W, Wen R, Laties AM (2006) Cell-based delivery systems: Development of encapsulated cell technology for ophthalmic applications. In: Jaffe JJ, Ashton P,.Pearson PA (eds) Intraocular drug delivery. Humana Press, New York, NY
Tao W, Wen R, Goddard MB 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
Zhu X, Li A, Brown B et al (2002) Mouse cone arrestin expression pattern: light induced translocation in cone photoreceptors. Mol Vis 8:462–471
Acknowledgments
We thank Dr. Cheryl Craft for anti cone-arrestin antibodies; Dr. Ying Song, Dr. Lian Zhao, and Yun Liu for technical assistance. Supported by Grants from NIH: R01EY015289 (RW), R01EY018586 (RW), R01EY001919 (MML), R01EY006842 (MML), Hope for Vision (RW), the James and Esther King Biomedical Research Program of the State of Florida (YL), the Department of Defense (W81XWH-09-1-0674, RW), and NIH Core Grants P30EY14801, P30EY002162, the Foundation Fighting Blindness (MML), and unrestricted grants from Research to Prevent Blindness, Inc., New York, NY to Bascom Palmer Eye Institute, Beckman Vision Center, and Scheie Eye Institute.
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Wen, R. et al. (2012). Regeneration of Cone Outer Segments Induced by CNTF. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_13
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DOI: https://doi.org/10.1007/978-1-4614-0631-0_13
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