Microarray expression analysis of the early N-methy-N-nitrosourea-induced retinal degeneration in rat

The study was undertaken to investigate the gene expressions in N-methy-N-nitrosourea (MNU)-induced rat retinal degeneration (RD) by performing microarray analysis of retinal RNA at 12 h. All rats were randomly divided into a normal group, a 12 h model group and a 24 h model group. Rats in the two model groups received a single intraperitoneal injection of 40 mg/kg body weight of MNU, while those in the normal group were injected with equivalent volume of physiological saline. After 12 h and 24 h of the injection, rats in each respective group were sacrificed, respectively. One eye of each animal was used for hematoxylin and erosin (H&E) staining, and fresh retinas of the other eye of each animal in the both normal group and 12 h model group were used to extract total RNA, which was analyzed by microarray and real time RT-PCR. Retinal histological alteration was found in the 24 h model group. There were 75 genes differently expressed (ratio ≥2.0), including 64 genes up-regulated and 11 genes down-regulated. Seven genes were assayed by real time RT-PCR and demonstrated the same alteration tendency as in microarray analysis. These genes that expressed differently mainly involved signal transduction, development, immune and defense, and apoptosis, etc. The major pathways were MAP-kinase signaling pathways, Toll-like receptor signaling pathway and apoptosis pathway involved. The results suggest that there are significant changes of gene expression in the early stage of MNU-induced RD. These microarray results provide clues to understand the molecular pathways underlying photoreceptor degeneration and indicate directions for future studies.