Subretinal Implantation of Microphotodiode Arrays: In vivo Assessment of Threshold and Spatial Activation

Abstract

Purpose: : Microphotodiode arrays (MPAs) have been proposed as a strategy to replace degenerate photoreceptors in humans with retinitis pigmentosa (RP). An important consideration is the threshold/duration of stimulation and spatial organization of the signal produced by the MPA. We examined the minimum stimulus intensity and spatial resolution of a silicon based MPA in an animal model of RP, the transgenic rat S334ter-Line 3 rhodopsin using in vivo electrophysiology.

Methods: : MPAs (1mm diameter devices) were implanted monocularly into the subretinal space of Tg-S334ter rats at two different ages (35 and 75 days of age). Placement in the superior retina was confirmed using OCT. The MPA was stimulated in situ with a scanning IR laser (905 nm) whose duration (0.1-4ms), power (0.19 - 15 mW) and spot size (200 - 1000μm) was varied. Multiunit extracellular activity was recorded from the superior colliculus (SC) of anesthetized rats at four post-implantation times (30, 90, 120 and 150 days). The area of the SC that responded to the IR stimulus was first mapped with full MPA stimulation. Stimulation threshold was determined as a function of IR intensity and duration. Spatial organization of the evoked response was studied with reduced beam sizes. Once the terminal experiment was completed, both eyes were removed and the retinas evaluated using light microscopic histology.

Results: : Stimulation of the entire MPA activated a local area of the SC that was retinotopically matched to the placement of the device in the retina. Within any of the fixed IR intensities, the response increased with pulse duration and 4ms produced the largest response. Threshold stimulation (4 SD above noise) was ~0.19mW with a 4ms pulse duration and ~11 mW with a 0.1 ms pulse duration. Our smallest stimulus diameter (200μm) produced a local response in the SC that was significantly smaller than the area of the response to larger stimuli. The position of activation in the SC changed as a function of the position of the stimulus.

Conclusions: : Threshold stimulation is well below levels of published ocular safety limits. The separation between areas of activation for small spots and corresponding retinotopy in SC indicates that this MPA device produces spatially localized stimulation and this information is transferred to the SC.

Keywords: degenerations/dystrophies • electrophysiology: non-clinical • superior colliculus/optic tectum