Differential gene expression pattern of diabetic rat retinas after intravitreal injection of erythropoietin

Background: To profile the pattern of gene expression in diabetic rat retinas with or without intravitreal injection of erythropoietin. Design: By using streptozotocin‐induced diabetic rats, after intravitreal injection of erythropoietin, neurosensory retinas were collected to determine the effect of erythropoietin on gene expression. Participants: Three groups of Sprague–Dawley rats were studied: normal control (15), diabetic rats with saline injection (15) and diabetic rats with intravitreal erythropoietin treatment (15). Methods: Diabetes was induced by intra‐peritoneal injection of streptozotocin. Intravitreal injection of erythropoietin was performed at the following time points: 0, 30 and 120 days after diabetes onset. Four days after each injection at above‐mentioned time points, the retinas were harvested for microarray assay. The real‐time PCR was used to evaluate the microarray data. Results: Genes encoding inflammatory factors, such as interleukin‐2 and interleukin‐11, which were upregulated in the diabetic retinas, were restored after erythropoietin treatment. Genes encoding pro‐apoptotic effectors, like Tnfrsf5, Bid3 and Bcl2l1, were also upregulated in diabetic rats and attenuated in erythropoietin‐treated group. In addition, real‐time PCR were employed to confirm the changes of the genes Trex2, G1P2, DHX58, RGD1311906 and LOC689064, which have not been reported in diabetic retinopathy. Conclusions: Intravitreal erythropoietin treatment is able to normalize the gene expression responsible for pro‐apoptotic and inflammatory responses noted in diabetic retinas.