| First Author | Coorey NJ | Year | 2015 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 56 |
| Issue | 4 | Pages | 2151-61 |
| PubMed ID | 25722214 | Mgi Jnum | J:230971 |
| Mgi Id | MGI:5766602 | Doi | 10.1167/iovs.14-15695 |
| Citation | Coorey NJ, et al. (2015) Differential Expression of IL-6/gp130 Cytokines, Jak-STAT Signaling and Neuroprotection After Muller Cell Ablation in a Transgenic Mouse Model. Invest Ophthalmol Vis Sci 56(4):2151-61 |
| abstractText | PURPOSE: It is anticipated that the interleukin-6/glycoprotein 130 (IL-6/gp130) family of cytokines and Jak-STAT signaling may be amenable to therapeutic manipulation for retinal diseases. Muller cells, which exhibit morphologic and functional changes in prevalent retinal diseases, are implicated in their induction and action. METHODS: We characterized expression of endogenous IL-6/gp130 cytokines and Jak-STAT signaling after inducible Muller cell ablation in the neural retinas of adult mice. This resulted in photoreceptor apoptosis and reactive activation of surviving Muller cells. Analysis was performed by using a combination of quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. Recombinant leukemia inhibitory factor (rLIF) was intravitreally injected in an attempt to inhibit photoreceptor degeneration following selective Muller cell ablation. RESULTS: Significant differential expression (both increases and decreases) of multiple IL-6/gp130 cytokines, such as LIF, oncostatin-M, and ciliary neurotrophic factor, occurred after Muller cell ablation, with concomitant increase in signal transducers and activators of transcription and extracellular kinases 1 and 2, particularly in surviving, activated Muller cells. Basic fibroblast growth factor was robustly increased in photoreceptors after selective Muller cell ablation. Multiple injections of rLIF failed to prevent photoreceptor degeneration. CONCLUSIONS: These results further characterize expression of IL-6/gp130 cytokines and Jak-STAT signaling in outer retinal disease, suggesting Muller cells are critical for their induction and action. Lack of rLIF-mediated neuroprotection contrasts with other retinal degenerations where Muller cell integrity remains intact or photoreceptor apoptosis occurs in a more rapid, synchronous manner. The presence of Muller cells may be critical for the functional benefits of rLIF and potentially other IL-6/gp130 cytokines. |
