Subretinal electrical stimulation preserves inner retinal function in RCS rat retina.

Area of Science:

• Ophthalmology and Vision Science
• Neuroscience
• Biomedical Engineering

Background:

• Subretinal electrical stimulation (SES) using a microphotodiode array (MPA) has shown promise in preserving retinal structure and function in Royal College of Surgeons (RCS) rats.
• Previous research indicates that SES upregulates Fgf2 expression and that the neuroprotective effects may be linked to current generated by electroretinography (ERG) test flashes.
• Weekly ERG testing demonstrated greater neuroprotection than biweekly or no testing, suggesting a dose-dependent relationship.

Purpose of the Study:

• To investigate whether the neuroprotective effects of SES in RCS rats increase in a dose-dependent manner with varying subretinal current levels.
• To explore the impact of increased current, generated by infrared (IR) light stimulation of the MPA, on retinal preservation.
• To differentiate the effects of SES from potential confounding factors associated with high-luminance white light used in standard ERG testing.

Main Methods:

• Royal College of Surgeons (RCS) rats underwent subretinal implantation of MPA devices, with the contralateral eye serving as a control.
• Four subretinal electrical stimulation (SES) groups were established: MPA only, low current (450 µA/cm2) once weekly (Low 1X), low current three times weekly (Low 3X), and high current (1350 µA/cm2) once weekly (High 1X).
• Infrared (IR) light was used to stimulate the MPA and increase current, with weekly electroretinography (ERG) recordings and Fgf2 expression analysis via real-time reverse-transcription PCR.

Main Results:

• All SES-treated eyes demonstrated significant preservation of electroretinography (ERG) parameters, including b-wave amplitude, implicit times, and post-receptoral function (Vmax, log σ), compared to untreated control eyes.
• The degree of retinal preservation was similar across all SES groups, irrespective of the increased current induced by IR light exposure.
• While SES-treated eyes showed a trend towards increased retinal Fgf2 expression, this upregulation did not correlate with the higher IR light intensities.

Conclusions:

• Subretinal electrical stimulation (SES) effectively preserves inner retinal function and signal transmission in RCS rats, beyond just photoreceptor protection.
• Increasing subretinal current induction via the MPA, using the employed IR stimulation method, did not yield improved neuroprotective outcomes.
• The findings suggest that the protective effects of SES may not be further enhanced by simply increasing current, or that the IR light stimulation did not adequately mimic the charge injection from standard ERG flashes.