Cytokine-induced SOCS expression is inhibited by cAMP analogue: Impact on regeneration in injured retina
Section snippets
Changes in SOCS mRNA expression in PN-grafted retinas after CNTF or combined CNTF/CPT-cAMP injections
There was very low SOCS1–3 mRNA expression in unstimulated, intact retina. The PN–ON graft procedure and intraocular saline injection resulted in only small changes in retinal SOCS1–3 mRNA levels, none of which were significant (Figs. 1A–C). Major changes in expression were, however, seen 2 h to 14 days after CNTF or combined CNTF/CPT-cAMP injections.
Discussion
CNTF stimulates the survival and growth of various types of injured neurons, but its effects are often transient and by no means all neurons in a given population are rescued. In the rat PN-ON graft model for example, in spite of repeated injections of recombinant CNTF, 3–4 weeks after PN transplantation only 15–20% of the adult RGC population remains viable, of which about 25% regenerate an axon (Cui et al., 2003, Park et al., 2004, Hu et al., 2007). The proportion of surviving adult RGCs that
Experimental methods
Young adult (8–10 weeks old) Fischer 344 rats were used in this study. All surgical procedures were approved by the Animal Ethics Committee of The University of Western Australia and conformed to national (NHMRC) guidelines.
Acknowledgments
We thank Greg Cozens for technical assistance. Supported by grants to ARH from the NHMRC and the WA Neurotrauma Research Program.
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2017, Experimental NeurologyCitation Excerpt :However, although CNTF and related chemokines of the cardiotrophin family become elevated in the eye after intraocular inflammation (Kurimoto et al., 2013; Leibinger et al., 2009), many studies report only weak effects of intraocular CNTF on regeneration in vivo (Lingor et al., 2008; Pernet and Di Polo, 2006; Qin et al., 2013; Smith et al., 2009; Weise et al., 2000) and in culture (Cohen et al., 1994; Yin et al., 2006, 2009). The low efficacy of CNTF appears to be a consequence of the increase in SOCS3, a repressor of the Jak-STAT signaling pathway, as RGCs mature, and socs3 deletion restores RGCs' ability of to respond to CNTF (Park et al., 2009; Qin et al., 2013; Smith et al., 2009). In the peripheral nerve grafting paradigm, high concentrations of CNTF augment axon regeneration (Cui and Harvey, 2000), but these effects are largely due to the trophic effects of CNTF on macrophages and are suppressed by using chlodrinate liposomes to eliminate macrophages (Cen et al., 2007).
- 1
Current address: Children’s Hospital and Department of Neurology, Harvard Medical School, Boston, MA 02215, USA.
- 2
Current address: Bascom Palmer Eye Institute, McKnight Vision Center, University of Miami, Fl 33136, USA.