STOM Promotes Retinal Angiogenesis in Diabetic Retinopathy via the ERK1/2/VEGFA Pathway

Diabetic retinopathy (DR) is a leading cause of blindness, but its underlying molecular mechanisms remain poorly understood. This study aimed to investigate the role of STOM in DR-related retinal angiogenesis and to elucidate its potential signaling mechanism.

A streptozotocin-induced diabetic rat model and human retinal microvascular endothelial cells (HRMECs) exposed to high glucose were employed. The expression levels of STOM, vascular endothelial growth factor A (VEGFA), and extracellular signal-regulated kinase (ERK1/2) pathway-related molecules were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunohistochemistry (IHC). Functional assays including Cell Counting Kit-8 (CCK-8), Direct cell counting, wound healing, Transwell migration, and Matrigel tube formation were performed to assess the effects of STOM knockdown or overexpression on HRMECs. The ERK1/2 inhibitor U0126 was applied to verify pathway dependence.

STOM expression was significantly upregulated in the retinas of diabetic rats and in HRMECs under high glucose conditions. STOM silencing suppressed high glucose-induced proliferation, migration, and angiogenic tube formation in HRMECs. Whereas STOM overexpression enhanced these pathological behaviors. Mechanistically, STOM promoted VEGFA upregulation and angiogenesis through activation of the ERK1/2 signaling pathway.

STOM facilitates pathological retinal angiogenesis in diabetic retinopathy via the ERK1/2/VEGFA signaling pathway. These findings identify STOM as a potential therapeutic target for DR.