AIM: To explore the role of microRNA-26a-5p (miR-26a) in early diabetic retinal neuronal cell death and reveal the underlying mechanism(s). METHODS: A streptozotocin (STZ)-induced diabetic mouse model was established using C57BL/6 J mice. Control or miR-26a mimic was intravitreally injected. Hematoxylin-eosin (H&E) and transmission electron microscopy (TEM) were used to observe the morphologic alterations in the retinal structure and ultrastructure, respectively. The expression of miR-26a and phosphatase and tensin homolog (PTEN) was assayed using qRT-PCR and western blotting, respectively. An immunofluorescence assay was used to investigate the distribution of PTEN expression in the retina. The expression of glial fibrillary acidic protein (GFAP) was measured to identify glial cell activation. The mRNA levels of IL-1β, NF-κB, and VEGF were examined to assess diabetic retinal inflammation. RESULTS: miR-26a expression was decreased in retinal tissues of diabetic mice, and injection of miR-26a mimic restored the miR-26a level. Diabetic mice had significantly reduced neuroretinal thickness and ganglion cell number; miR-26a mimic delayed the thinning of neuroretinal layers and the loss of ganglion numbers. TEM showed damaged ultrastructure of retinal ganglions in diabetic mice, while miR-26a mitigated the damages. PTEN expression was increased mainly in the inner and outer nuclear layer of the retina in diabetic mice; miR-26a mimics lowered PTEN expression. GFAP, IL-1β, NF-κB, and VEGF expression were significantly increased in the diabetic mice, and intravitreal delivery of miR-26a resulted in a down-regulated expression of these factors. CONCLUSION: miR-26a can protect against retinal neuronal impairment in diabetic mice by down-regulating PTEN, highlighting the potential of miR-26a as a target for DR treatment.
AIM: To explore the role of microRNA-26a-5p (miR-26a) in early diabetic retinal neuronal cell death and reveal the underlying mechanism(s). METHODS: A streptozotocin (STZ)-induced diabetic mouse model was established using C57BL/6 J mice. Control or miR-26a mimic was intravitreally injected. Hematoxylin-eosin (H&E) and transmission electron microscopy (TEM) were used to observe the morphologic alterations in the retinal structure and ultrastructure, respectively. The expression of miR-26a and phosphatase and tensin homolog (PTEN) was assayed using qRT-PCR and western blotting, respectively. An immunofluorescence assay was used to investigate the distribution of PTEN expression in the retina. The expression of glial fibrillary acidic protein (GFAP) was measured to identify glial cell activation. The mRNA levels of IL-1β, NF-κB, and VEGF were examined to assess diabetic retinal inflammation. RESULTS: miR-26a expression was decreased in retinal tissues of diabetic mice, and injection of miR-26a mimic restored the miR-26a level. Diabetic mice had significantly reduced neuroretinal thickness and ganglion cell number; miR-26a mimic delayed the thinning of neuroretinal layers and the loss of ganglion numbers. TEM showed damaged ultrastructure of retinal ganglions in diabetic mice, while miR-26a mitigated the damages. PTEN expression was increased mainly in the inner and outer nuclear layer of the retina in diabetic mice; miR-26a mimics lowered PTEN expression. GFAP, IL-1β, NF-κB, and VEGF expression were significantly increased in the diabetic mice, and intravitreal delivery of miR-26a resulted in a down-regulated expression of these factors. CONCLUSION: miR-26a can protect against retinal neuronal impairment in diabetic mice by down-regulating PTEN, highlighting the potential of miR-26a as a target for DR treatment.