Neuroprotection of Photoreceptors in the RCS Rat After Implantation of a Subretinal Implant in the Superior or Inferior Retina

Abstract

The artificial silicon retina (ASR^TM) consists of an array of photodiodes on a silicon disk that responds to incident light in a gradient fashion (Peyman et al., 1998; Chow et al., 2001, 2002). This device is designed to be placed in the subretinal space and serve as a replacement for degenerating photoreceptors. Two possible mechanisms for the ASR device to improve visual function include 1) direct activation of the remaining inner retinal neurons and subsequent activation of visual centers in the brain or 2) a delay in photoreceptor loss due to a neurotrophic effect from subretinal electrical stimulation. Initial results of ongoing FDA trials with the ASR device suggest that subretinal electrical stimulation could elicit a neurotrophic effect (Chow et al., 2004). Ten advanced retinitis pigmentosa (RP) patients implanted with the ASR device have increased central visual fields and improved visual acuity and color vision (Chow et al., 2004). These improvements cannot be easily explained by direct activation since the implant was placed 20° from the macula. To determine whether neuroprotection results from subretinal electrical stimulation, the RCS rat model of RP was implanted with an ASR device. Subretinal implantation of an ASR device into the superior retina of the Royal College of Surgeons (RCS) rat resulted in preservation of photoreceptors (Pardue et al., 2004). However, the RCS rat is known to have delayed photoreceptor degeneration in the superior region of the retina (LaVail and Battelle, 1975). To determine whether the superior retina is a “privileged” site in the RCS rat, ASR devices were subretinally implanted in the superior and inferior retina.