Expression Of Hif-1 Alpha And Robo4 In The Retinas Of Streptozotocin-Induced Diabetic Mice

Purpose: This study investigated the expression of HIF-1 alpha and Robo4 in the retinas of streptozotocin (STZ)-induced mice and determined the expression correlation of these two factors in early diabetic retinas in vivo. Methods: A high-fat diet together with STZ stimulated type 2 diabetes mellitus (DM). HE staining was used to observe the morphologic features of the retinas following 4, or 8 weeks of hyperglycemia. Immunofluorescence was carried out to analyze the expression of HIF-1 alpha and Robo4 in the retinas at different time points. HIF-1 alpha and Robo4 mRNA and protein expressions were quantified by real-time PCR and western blot. Results: The arrangements of the retinal nerve fiber layer (NFL) and the ganglion cell layer (GCL) were slightly turbulent in the 4-week old diabetic mice, which became aggravated by NFL edema and cytoplasmic vacuoles in the 8-week old group. In the 4-week old group, HIF-1 alpha was expressed slightly higher in NFL and GCL, and Robo4 expression increased in NFL and GCL. In the 8-week old diabetic retinas, HIF-1 alpha expression was enhanced in NFL, GCL, and the outer plexiform layer (OPL); Robo4 expression increased apparently in NFL and GCL. HIF-1 alpha and Robo4 mRNA and protein expressions were also increased slightly in the 1-week old retinas and significantly after 4 and 8 weeks. Conclusions: With aggravating retina structure turbulence in DM mice, both HIF-la and Robo4 expressions were increased and mainly concentrated in the GCL, INL, and OPL, suggesting a regulatory role of HIF-1 alpha on Robo4 and their combined effect on DM retina damage in vivo.