In Vitro Evaluation of Apoptosis, Inflammation, Angiogenesis, and Neuroprotection Gene Expression in Retinal Pigmented Epithelial Cell Treated with Interferon α-2b

Abstract

Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the in vitro effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (BCL-2, BAX, BDNF, VEGF, and IL-1b) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of BCL-2, BAX, BDNF, and IL-1b; however, the BCL-2/BAX ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that VEGF expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe (BCL-2/BAX ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.

Keywords: IFN α-2b; RPE; angiogenesis; apoptosis; inflammation; neuroprotection.