Optimizing stimulation parameters: transpalpebral and transbrain electrical stimulation for retinal protection in RCS rats.

INTRODUCTION

Retinitis pigmentosa is a genetically heterogeneous retinopathy causing photoreceptor death and blindness. Electrical stimulation is a promising non-invasive neuroprotective strategy. This study investigated the neuroprotective effects of transpalpebral ES (TpES) and transbrain ES (TbES) delivered at Gallbladder meridian acupoints (GB14, GB16, GB20) in Royal College of Surgeons (RCS) rats, and identified optimal parameters for each modality.

METHODS

RCS rats were randomized to control, sham, TpES (200, 400, 600, 800 µA), and TbES (15, 30, 50, 100 Hz) groups. Stimulation was given daily for 14 days from 6 weeks of age. Visual-guided behavior was assessed by open-field test (OFT). Retinal function and morphology were evaluated by electroretinography (ERG), color fundus photography (CFP), spectral-domain optical coherence tomography (SD-OCT), and histopathology. Photoreceptor apoptosis was quantified by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Neurotrophic factors (BDNF, CNTF, bFGF, NGF) and c-Fos were detected by immunofluorescence and digital PCR.

RESULTS

OFT revealed progressive anxiety-like behavior in untreated control rats, though non-visual confounds cannot be excluded. All stimulated groups exhibited stable locomotor activity comparable to sham, with no behavioral abnormalities or systemic adverse effects. All stimulated groups showed stable locomotor activity comparable to sham, with no adverse effects. TpES at 800 µA and TbES at 50 Hz produced the greatest preservation of retinal function and structure, maintaining 3-4 photoreceptor cell layers versus 1-2 layers in controls. TpES at 800 µA reduced the apoptotic index by ∼35%; all TbES frequencies lowered it to a similar range, indicating a frequency-independent anti-apoptotic threshold. Both modalities upregulated BDNF and bFGF; TbES-especially at 50 Hz-additionally upregulated CNTF and NGF, a pattern not seen in TpES groups. Elevated c-Fos confirmed inner retinal neuron activation.

CONCLUSION

Optimized TpES (800 µA) and TbES (50 Hz) each exert neuroprotective effects, preserving retinal function and structure, reducing apoptosis, and upregulating neurotrophic factors, without behavioral or systemic side effects. These eye-brain ES approaches, grounded in traditional Chinese medicine meridian theory and modern neuromodulation, provide evidence-based parameters for clinical translation and represent a promising synergistic strategy.