Abstract
Aims: Diabetic retinopathy is the most common microangiopathy in diabetes. It is morphologically characterized by vasoregression including pericyte loss and increased formation of acellular capillaries. Recently, we characterized a transgenic rat with a universal overexpression of PKD-2, in which c- terminal polycystein-2 is truncated. The transgenic rats showed severe vasoregression in the retinas at the second month of life. To elucidate the mechanisms of vasoregression in the retina, we analysed transcriptional alterations in this transgenic rats. Materials and methods: Profiles of gene expression were evaluated in rats before and after vasoregression, at the first and the third month of life, respectively. Age-matched SD rats served as controls. RNA was isolated from individual retinas and microarray analysis was performed with affymetrix gene chips according to the protocols published (http://www.ma.uni-heidelberg.de/inst/zmf/affymetrix/). Results: Numerous genes were altered during retinal vasoregression. 3267 genes were upregulated while 2924 genes were significantly downregulated (cutoff p<0.001). Serine/cysteine peptidase inhibitor, lectin-galactose binding and CD74 antigen are the highest (approximately 6-fold) upregulated genes. A number of genes related to neuronal cells, glial cells and endothelial cells were regulated in 3-month transgenic retinas compared to control SD retinas. Analysis of signalling clusters showed many signalling pathways were significantly involved during vessel degeneration in the retina. The most significant pathways include fatty acid elongation in mitochondria, mRNA splicing, adipocytokine signaling pathways and antigen processing and presentation pathways. Conclusion: Our data from microarray analysis of a new transgenic rat, a model for vasoregression of diabetic retinopathy, suggests that we have identified a number of genes and pathways which are involved in the development of retinal vasoregression. Further analysis of such genes may provide new insights for discovering new mechanisms underlying vasoregression also in diabetic retinopathy.
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