Autophagy and exosome secretion in photoreceptor and RPE cells are crucial during diabetic retinopathy (DR). Thioredoxin (Trx) upregulation delays diabetes-induced photoreceptor cell degeneration; however, the impact of autophagy and exosome secretion on it remains poorly understood. The present study, thus, investigated their effect on Trx upregulation to delay diabetes-induced photoreceptor cell degeneration and identified the potential therapy for DR in the future.

The study used Trx-transgenic mice and 661w cells as models. It evaluated Retinal function and morphology by electroretinography and H&E staining, apoptosis by TUNEL staining, protein expression by Western blotting, and autophagy by TEM and mRFP-GFP-LC3 method.

The study observed-

• Trx upregulation can delay diabetes-induced photoreceptor cell degeneration, both in vitro and in vivo
• Trx overexpression caused a decrease in the expression of LC3 and p62 and an increase in the expression of Alix and CD63. However, it inhibited after AMPK inhibitor treatment.
• RPE cells phagocytosed secreted exosomes from photoreceptors to regulate their physiological function.

This study shows that Trx upregulation has the potential to delay diabetes-induced photoreceptor cell degeneration through AMPK-mediated autophagy and exosome secretion. RPE cells in DR can phagocytose and degrade secreted exosomes from photoreceptor cells.

Ren X, Lv J, Wang N, et al. Thioredoxin upregulation delays diabetes-induced photoreceptor cell degeneration via AMPK-mediated autophagy and exosome secretion. Diabetes Research and Clinical Practice. 2022;185. https://doi.org/10.1016/j.diabres.2022.109788.