# Combined thermal and mild electrical stimulations modulate heat shock protein and VEGF in retinal pigment epithelial cells under high glucose

## TL;DR

Combining heat and mild electrical stimulation may help treat diabetic macular edema by boosting protective proteins and reducing harmful factors in eye cells.

## Contribution

This study demonstrates that combining thermal and mild electrical stimulation modulates HSP70 and VEGF in RPE cells under high glucose conditions.

## Key findings

- Combined thermal and mild electrical stimulation increased HSP70 expression in RPE cells.
- The treatment suppressed VEGF and inflammatory cytokine levels in a high glucose model.
- The treatment showed a transient protective effect on blood-retinal barrier integrity.

## Abstract

Macular laser for diabetic macular edema (DME) is known to increase heat shock protein (HSP) expression in retinal pigment epithelial (RPE) cells, and increased HSP expression may be a mechanism for improving macular edema. Furthermore, the effectiveness of mild electrical stimulation (MES) as a cofactor in further enhancing HSP expression by thermal stimulation has been reported. In the current study, the effect of this combination treatment was examined in an in vitro HG (high glucose) + DFX (deferoxamine mesylate salt) model that simulates DME using a human RPE cell line (ARPE-19).

Combined thermal stimulation and MES significantly increased HSP70 expression in both the control and HG + DFX model groups, while suppressing VEGF and inflammatory cytokine levels in HG + DFX model. The combined treatment also showed a protective effect on the blood-retinal barrier integrity, although transient, as measured by TEER. These findings suggest that combined thermal stimulation and MES represent a promising therapeutic approach for managing DME, by modulating HSP and VEGF expression and potentially reducing inflammation and promoting protective mechanisms in the retina.

The online version contains supplementary material available at 10.1186/s13104-025-07539-y.