DNA microarray analysis of the gene expression changes in retinal neuronal cell death.

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Two experimental models were used in this study. The first model was rat retinal is3chemia-reperfusion model. In this model, gene expression changes were systematically studied by using DNA microarrays that displayed more than 10,000 genes and ESTs. The number of genes that showed up-regulation of more than 3 folds was as many as 135 genes and such genes can be grouped into 6 different groups. (1) transcription factors (2) cell cycle-related genes (3) stress responsive genes (4) cell signaling genes (5) cell adhesion molecule genes (6) protease genes. Expression changes of some genes that belongs (1),(2),and (3) were also studied by the real time PCR analysis. In this model, importance of transcription factors and cell cycle-related genes was shown. The second model used was monkey glaucoma model. Ocular hypertension was induced in monkey eyes by laser photocoagulation of the trabecular meshwork. In this model, gene expression changes in the sensory retina were studied by using a human DNA microarray because ready-made monkey microarrays were not available. Contrary to the rat retinal ischemia-reperfusion model, the profile of gene expression changes found in the monkey glaucoma model was different from that found in the rat ischemia-reperfusion model. Only 0.7% of the genes studied showed up-regulation of more than 1.7 folds of the control. Among them, ceruloplasmin showed up-regulation and the expression changes were validated by the real time PCR, analysis and immunohistochemical studies. Three peer-reviewed papers have been published through the present study.