Mol Neurobiol. 2026 Sep 7;63(1):881. doi: 10.1007/s12035-026-06186-z.
ABSTRACT
Diabetic retinopathy (DR) is a common late-stage complication of diabetes and a leading cause of vision loss. Oxidative stress plays a crucial role in DR progression by activating stress pathways and altering gene expression. This study investigated the effect of Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a ROS scavenger, on diabetes-induced transcriptomic changes in the neural retina of Wistar rats. Twelve-week-old male Wistar rats (n = 5 per group) were divided into four groups: control, control with Tempol (25 mg/kg/day), streptozotocin-induced diabetic (STZ 50 mg/kg), and diabetic with Tempol. Animals were maintained for 12 weeks with weekly monitoring of body weight and blood glucose. Neural retinas were dissected and preserved in RNAlater. Total RNA was extracted, and microarray analysis was used to assess expression of over 22,000 genes. Selected genes (Stat1, Txnip, Aif1, Gfap, and Opn1sw) were validated using quantitative real-time PCR. Diabetic retinas exhibited 494 differentially expressed genes. Upregulated genes were primarily linked to oxidative stress, immune activation, and inflammatory pathways, whereas downregulated ones were associated with retinal structure and function. Tempol-treated diabetic rats exhibited substantially fewer transcriptomic alterations when compared to diabetic rats, indicating attenuation of diabetes-induced oxidative stress and glial activation. The number of altered genes from control were lower by 73% in the diabetic Tempol-treated group compared with untreated diabetic rats, indicating a normalizing effect. Tempol attenuates diabetes-induced oxidative and inflammatory stress, supporting its potential as an intervention in diabetic retinopathy.
PMID:42704527 | DOI:10.1007/s12035-026-06186-z