Txnip/Trx Is a Potential Element in Regulating O-GlcNAc Modification in Photoreceptors to Alleviate Diabetic Retinopathy.

Hyperglycemia is a key factor in diabetic retinopathy which leads to blindness. O-linked-N-acetylglucosamine (O-GlcNAc) modification changes are linked to various diseases, including diabetic retinopathy. This research aims to study the roles of Txnip and Trx in influencing O-GlcNAc in photoreceptor cells during diabetic retinopathy. A diabetic mouse model and 661w cells, after exposure to high glucose, were employed as models. H&E staining and ERG were used to evaluate the morphology and function of the retina, respectively. Western blotting was used to analyze protein expression, a TUNEL assay was used to measure apoptosis, and a co-immunoprecipitation (CO-IP) assay was used to detect the interactions of protein. In diabetic mice, electroretinogram (ERG) amplitude wave, retinal thickness, and body weight decreased. Glial fibrillary acidic protein (GFAP), Iba1 expression, and blood glucose level increased. In vitro, the percentage of apoptotic cell, Bax, and caspase3 levels increased, and Bcl2 decreased in 661w cells under high-glucose conditions. Moreover, Txnip expression was upregulated, while Trx was downregulated. Additionally, a Western blot analysis revealed that high-glucose exposure led to increased O-GlcNAc modification both in vivo and in vitro. The CO-IP results show that Txnip interacted with O-GlcNAc modifications. S-opsin expression was significantly downregulated in vitro under high-glucose conditions. Knockdown Txnip or upregulation Trx could reverse or delay apoptosis in 661w cells under hyperglycemic conditions. Txnip/Trx is a potential element in regulating photoreceptor apoptosis in diabetic retinopathy. The underlying mechanism is linked to regulation of O-GlcNAc modification in photoreceptor cells in DR.