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Antonia M. Joussen, Sui Huang, Vassiliki Poulaki, Kevin Camphausen, Wolf-Dietrich Beecken, Bernd Kirchhof, Anthony P. Adamis; In Vivo Retinal Gene Expression in Early Diabetes. Invest. Ophthalmol. Vis. Sci. 2001;42(12):3047-3057.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. Studies have demonstrated a causal role for specific molecules in the
pathogenesis of diabetic retinopathy. Among the implicated mediators
are growth factors such as vascular endothelial growth factor (VEGF) as
well as adhesion molecules and proliferation- and apoptosis-related
genes. However, a coordinated large-scale investigation of gene
expression in the diabetic retina has not yet been reported. Here the
retinal gene expression profile of diabetic and nondiabetic animals
using cDNA microarrays were analyzed and compared.
methods. Long–Evans rats were made diabetic with streptozotocin. Retinal gene
expression was analyzed over 3 weeks using high-density nylon
filter–based cDNA arrays. Genes were sorted into clusters according to
their temporal expression profiles. They were also grouped according to
their potential pathophysiological significance. The in vivo gene
expression profiles of selected genes were verified via RNase
results. The rat GeneFilter contains a total of 5147 genes, of which 1691 are
known genes and 3456 are expressed sequence tags (ESTs). On day 3, the
expression of 27 known genes was increased by more than twofold. On
days 7 and 21, the corresponding numbers were 60 and 12, respectively.
A transient upregulation (>2-fold) in expression was seen in 627 of
5147 total genes. A subset of 926 genes exhibited a modest (<2-fold)
decrease in expression. No genes showed a greater than twofold decrease
in expression. Overall, the identity of the genes that were upregulated
suggests that the response of the retina to the diabetic challenge
contains an inflammatory component. Moreover, most regulatory activity
occurs during the first week of diabetes.
conclusions. The development of a rational therapy for diabetic retinopathy will be
assisted by detailed knowledge regarding the molecular pathophysiology
of the disease. Here, an expression profile of an underlying retinal
inflammatory process in early diabetes was extracted. Beyond providing
insight into the general nature of the response to a pathogenic
challenge, gene expression profiling may also allow the efficient
identification of potential drug targets and markers for monitoring the
course of disease.
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