SUMO1/UBC9‑decreased Nox1 activity inhibits reactive oxygen species generation and apoptosis in diabetic retinopathy.

Diabetic retinopathy (DR) is an increasing global health concern that causes vision loss and blindness. Reactive oxygen species (ROS) are considered to be a principal cause of DR. An important source of ROS is the oxidization of NADPH. In the present study, NADPH oxidase 1 (Nox1)‑expressing human retinal epithelial cell (HREC) lines were generated and infected with small ubiquitin‑like modifier 1 (SUMO1) and/or ubiquitin conjugating enzyme E2 I (UBC9) lentiviral pGMLV constructs. The viabilities, apoptotic capacities and ROS production levels of the HREC lines were quantified using Hoechst 33258, annexin V/propidium iodide and dichlorodihydrofluorescein diacetate assays, respectively. Additionally, rat DR models were established. From these models, the apoptotic capacities of retinal tissues were visualized using terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and the pathologies were evaluated. The mRNA and protein expression levels of SUMO1, UBC9 and Nox1 were analyzed using reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. Compared with controls, the relative mRNA levels of SUMO1 and UBC9 were significantly upregulated, and the Nox1 levels significantly downregulated, in cells infected with SUMO1 or UBC9 alone or in combination. The ROS production and apoptosis rates of cells and retinal tissues were decreased. In addition, pathological symptoms in DR tissues improved when they were simultaneously transfected with SUMO1 and UBC9 via intraocular injection. In conclusion, the SUMO1/UBC9 axis may regulate Nox1‑mediated DR by inhibiting ROS generation and apoptosis in rat and cellular model systems.