ABSTRACT

Background:

Retinal prostheses were developed to provide artificial vision to people suffering from debilitating outer retinal degenerative disorders. In retinitis pigmentosa and age-related macular degeneration, although the photoreceptors undergo progressive and significant degeneration, the ganglion cells and bipolar cells remain relatively intact. Visual percepts can be created by electrically stimulating these remaining neurons, resulting in the subjects’ improved ability to detect motion and navigate. Electrical stimulus parameters such as charge, charge density and stimulus frequency are critical when improving retinal prosthesis design, because these parameters will define the safe operating range for the retinal prosthesis, which must balance the need to provide effective stimulation to cause neural excitation with the requirement to operate within limits of stimulation protocols that are deemed safe. Toward this end, the present study focused on determining the effect of electrical stimulation of the retina in a rabbit model.

Methods:

A total of 12 rabbits were studied. The rabbits received an anesthesia combination of ketamine (100 mg kg−1; KETASET, Fort Dodge, IA, USA), xylazine (20 mg kg−1; X-Ject SA, Butler, Dublin, OH, USA), and sometimes sevoflourane (1% in 100% O2) through a gas-inhalant mask for the entire duration of the experiment. Retinal stimulation was carried out using a concentric monopolar electrode (custom made, FHC Inc., Bowdoin, ME, USA), measuring 250µm diameter with a flat tip Platinum-Iridium (90%/10%). The stimulating electrode was modified by forming a high surface area Platinum- Iridium film on the surface of the electrode. We used biphasic, cathodic first current pulses delivered to the stimulation electrode for 30, 45 and 100 minutes with each pulse phase 1 ms long without any interphase delay. We tested 3 different currents [450 µA (0.92 mC/cm2), 600 µA (1.22 mC/cm2) and 800 µA (1.63 mC/cm2)] and 3 different frequencies (20, 100, 333 Hz). OCT imaging was performed every 3 minutes with the Bioptegen OCT (Bioptegen, Durham, NC) or the Heidelberg Spectralis OCT (Heidelberg Engineering, Franklin, MA). The rabbits were followed up every three days (±1 days) for up to 2 weeks’ duration. The groups that showed no change in retinal thickness during the stimulation procedure was re-imaged 24 hours later, while the group that showed retinal thickening was kept for 2 weeks to evaluate whether the change persisted. The stimulation protocol for our survival study are summarized in Table 1.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 1: Stimulation protocol for survival experiments

Results:

Our study showed that both stimulus frequency and intensity play an important role in the change of retinal thickness. The results were consistent across the different combinations of charge density and stimulus frequency employed (Table 2).

 

 

 

 

 

 

 

 

 

Table 2: Change in retinal thickness with electrical stimulation

Furthermore, the retinal thickening was still observed two weeks after stimulation (Figure 1).

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1: OCT images demonstrating persisting retinal thickening following 2-week survival after retinal stimulation with 450 (0.92 mC/cm2) µA current, 333 Hz, 1 ms biphasic pulse for 30 minutes. Yellow arrow shows the opaque reflection of the stimulated electrode. Red rectangle depicts area of retinal thickening.

Conclusion:

Electrical stimulation of the retina at high rates and high charge density can create long-lasting retinal thickening. Safety studies should consider both intensity and rate of stimulation; this retinal thickening was not seen when a given intensity (charge density) was delivered at a low rate (pulses/second). The exact nature of the thickening remains unclear and will be studied in future experiments.

Disclosures:

James D. Weiland has a commercial interest in Pt/Ir electrode materials. Research funding by NEI EY022931 and Research to prevent blindness


CONTACT DETAILS

Alejandra Gonzalez Calle, V. Swetha E. Jeganathan*, James D. Weiland
University of Michigan
Ann Arbor
United States
Email : jvswetha@med.umich.edu
Cell Phone: +17345126456
Work Phone: +17345126456