A molecular mechanism of optic nerve regeneration in fish: The retinoid signaling pathway

Publication date: November 2013 Source:Progress in Retinal and Eye Research, Volume 37 Author(s): Satoru Kato , Toru Matsukawa , Yoshiki Koriyama , Kayo Sugitani , Kazuhiro Ogai The fish optic nerve regeneration process takes more than 100 days after axotomy and comprises four stages: neurite sprouting (1–4 days), axonal elongation (5–30 days), synaptic refinement (35–80 days) and functional recovery (100–120 days). We screened genes specifically upregulated in each stage from axotomized fish retina. The mRNAs for heat shock protein 70 and insulin-like growth factor-1 rapidly increased in the retinal ganglion cells soon after axotomy and function as cell-survival factors. Purpurin mRNA rapidly and transiently increased in the photoreceptors and purpurin protein diffusely increased in all nuclear layers at 1–4 days after injury. The purpurin gene has an active retinol-binding site and a signal peptide. Purpurin with retinol functions as a sprouting factor for thin neurites. This neurite-sprouting effect was closely mimicked by retinoic acid and blocked by its inhibitor. We propose that purpurin works as a retinol transporter to supply retinoic acid to damaged RGCs which in turn activates target genes. We also searched for genes involved in the second stage of regeneration. The mRNA of retinoid-signaling molecules increased in retinal ganglion cells at 7–14 days after injury and tissue transglutaminase and neuronal nitric oxide synthase mRNAs, RA-target gen...
Source: Progress in Retinal and Eye Research - Category: Opthalmology Source Type: research