Protective effects of rosiglitazone on retinal neuronal damage in diabetic rats

To investigate whether rosiglitazone has a protective effect on retinal neural cells in diabetic rats, and to determine a possible anti-apoptotic mechanism.

Streptozotocin-induced diabetic rats and control animals were randomized evenly to receive rosiglitazone or not, effects were examined after 24 weeks. Retinal histology was examined and quantified using light microscopy; Apoptosis of retinal neural cells was determined by terminal dUTP nick-end labeling assay; Retinal ultrastructure was examined by transmission electron microscopy; Proteins levels of cleaved caspase-3, signal transduction and activators of transcription-3 (STAT3), phospho-STAT3 (p-STAT3), and suppressors of cytokine signaling 3 (SOCS3) in the retinal tissues were also determined by western blotting.

Compared with the control group, the thickness of the overall retina, inner plexiform layer, inner nuclear layer reduced by 13.8%, 27.4% and 4.2%, respectively (p < 0.05) in the diabetic group after 24 weeks; The number of cells in the ganglion cell layer was also decreased by 18.6% (p < 0.05). There was apoptosis of retinal neurons in the diabetic rats. Diabetes also induced mitochondrial metamorphosis in ganglion cells and evident pyknosis in the outer nuclear layer. These effects were associated with increased levels of cleaved caspase-3, p-STAT3, and decreased levels of SOCS3. After treatment of rosiglitazone, the thickness of the retina and the number of cells in the ganglion cell layer were significantly greater than those in the diabetic group (p < 0.05). Rosiglitazone also attenuated the diabetic-induced apoptosis of retinal neurons and mitochondrial metamorphosis in ganglion cells. Consistent with these effects, rosiglitazone treatment also decreased cleaved caspase-3 and p-STAT3 expression and, at the same time, increased SOCS3 expression.

Rosiglitazone attenuated diabetes-induced apoptosis in retinal neurons through activities that may involve inhibition of p-STAT3 by induction of SOCS3, which suggested that rosiglitazone might be used to prevent retinal neuronal damage in diabetes mellitus.