Investigative Ophthalmology & Visual Science
Targeting Endoplasmic Reticulum Stress With Exogenous GDNF Promotes Diabetic Corneal Epithelial and Neural Repair via PI3K/AKT Signaling
By 昊宇 李, Jianfeng Long, Shirui Dai and 3 others.
Abstract
Purpose
This study investigates the therapeutic potential and the core signaling associated with glial cell line-derived neurotrophic factor (GDNF) in alleviating diabetic keratopathy (DK).
Methods
In vitro, human corneal epithelial cells (HCECs) were subjected to glucolipotoxic stress to simulate the type 2 diabetes mellitus (T2DM) microenvironment, with or without GDNF and PI3K/AKT pathway modulators. In vivo, a T2DM mouse model was established using a combination of high-fat diet feeding and streptozotocin administration, and recombinant GDNF was administered subconjunctivally. Cellular functions were evaluated using standard assays. Protein expressions in HCECs, murine corneas, and trigeminal ganglia (TG) were quantified via Western blotting. Ultrastructural endoplasmic reticulum (ER) alterations were observed using transmission electron microscopy. Clinical evaluations, including fluorescein staining, mechanical sensitivity, and wound healing rates were systematically conducted alongside whole-mount corneal nerve immunolabeling.
