Abstract
Purpose :
Diabetic neurotrophic keratopathy (DNK) significantly impacts the quality of life for diabetic patients, leading to delayed corneal wound healing, reduced nerve density, and impaired corneal sensation. Very limited treatment has been proven effective for DNK. Transpalpebral electrical stimulation (TpES) non-invasively delivers microcurrent electricity to the eye via orbital skin. This study investigates the neuroregenerative potential of TpES in a type I diabetes mellitus (DM)-induced DNK model and delves into the mechanism of electrical-induced neuroregeneration.
Methods :
Male C57BL6J mice were induced with type I DM through intraperitoneal streptozotocin (STZ) injection. Starting at week 15 post-STZ, daily 4-minute TpES sessions were administered for 14 days. Sham controls received electrode placement without current, while non-STZ mice served as blanks. Corneal wholemount analysis targeting beta-III-tubulin and bulk RNA sequencing using Illumina Novaseq were employed for nerve observation and mechanistic insight, respectively.
Results :
Six weeks post-STZ, a progressive loss of subbasal plexus nerve fibers was observed. Following the 2-week TpES treatment, the TpES group exhibited significantly higher plexus density with an intact central whirl, contrasting with decreased density and disrupted structure in the sham control (Fig 1). Isolated trigeminal ganglia (TG) neurons from the TpES group displayed significantly longer neurites than sham controls, indicative of direct neuronal stimulation. Corneal fluorescein staining (CSF) at 17 weeks post-STZ showed a significant epithelial defect in sham group, while minimal defect was observed in TpES group or blank. We collected TG from mice underwent 2 weeks of daily 4min TpES and conducted bulk RNA sequencing analysis. We noted a significant upregulation of genes involved in Ca2+ transport (Cacng7, and Tpcn1) and growth factors (Fgf6, Megf11, Atf5) in TpES mice compared to sham controls.
Conclusions :
TpES effectively restores corneal nerve density and protects the corneal epithelium in a type I DM model. The neuroregenerative effect is related to increased Ca2+ transport and increased expression of growth factors.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.