| First Author | Zhu L | Year | 2015 |
| Journal | J Neurochem | Volume | 133 |
| Issue | 6 | Pages | 909-18 |
| PubMed ID | 25692504 | Mgi Jnum | J:309910 |
| Mgi Id | MGI:6708313 | Doi | 10.1111/jnc.13075 |
| Citation | Zhu L, et al. (2015) Dysregulation of inter-photoreceptor retinoid-binding protein (IRBP) after induced Muller cell disruption. J Neurochem 133(6):909-18 |
| abstractText | Reduced expression of a ~150 kDa protein was unexpectedly observed while investigating Norrin protein in a transgenic murine model in which Muller cells can be selectively and inducibly disrupted. Isolation of this unknown protein via ion exchange and hydrophobic interaction chromatography followed by Tandem mass spectrometry identified it as Inter-photoreceptor retinoid-binding protein (IRBP). Significantly reduced IRBP mRNA expression was observed at the early and late stages after Muller cell disruption. IRBP protein expression was also consistently reduced to 5.7% of the control level as early as 1 week after Muller cell disruption. This down-regulation of IRBP was accompanied by focal hyperfluorescent dots and cytotoxic N-retinylidene-N-retinylethanolamine (A2E) accumulation. In vitro treatment of cone photoreceptor cell lines with conditioned medium collected from stressed Muller cells suggested that Muller cells regulated photoreceptors expression of IRBP via secreted factor(s). In vivo studies suggested that one of these secreted factors was tumour necrosis factor alpha (TNFalpha). These findings suggest that dysregulation of IRBP expression caused by Muller cell dysfunction may be an important early event in photoreceptor degeneration in some retinal diseases. This study reports down-regulation of inter-photoreceptor retinoid-binding protein (IRBP) in photoreceptors and retinoid cycle derangement after Muller cell disruption in a transgenic mouse model. The findings indicate that Muller cells communicate with photoreceptors in response to stress by secreting soluble protein factor(s). We propose that down-regulation of IRBP may represent an early and novel pathogenic mechanism in degenerative retinal diseases. |
