Neuroprotective Effect of Subretinal Implants in the RCS Rat

Pardue, Machelle T.; Phillips, M.; Yin, Hang; Sippy, Brian D.; Webb-Wood, Sarah; Chow, Alan Y.; Ball, Sherry L.

doi:10.1167/iovs.04-0515

Cited by 101 publications

(110 citation statements)

References 49 publications

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“…Transcorneal electrical stimulation applied weekly for 2 to 6 weeks prolonged PR survival and delayed the decrease in retinal function in RCS rats. 50 Using a subretinal implant, electrical stimulation also preserved the ERG responses 51,52 as well as the visual-evoked responses in the superior colliculus 53 of RCS rats. In our experimental conditions, the electrical field in between the two electrodes did not cover the retina and was applied only for o2 s, which makes it very unlikely that such retinal electrostimulation could occur.…”

Section: Discussionmentioning

confidence: 95%

Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose

et al. 2011

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Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneration time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 mg of GDNF-encoding plasmid in the rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS rats. Unexpectedly, increasing the GDNF secretion level accelerated PR degeneration and the loss of electrophysiological responses. This is the first report: (i) demonstrating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administration of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.

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Section: Discussionmentioning

confidence: 95%

Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose

et al. 2011

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“…Because of the decrease in implant activity over the follow-up period, further studies will be needed to determine if this MPA design will continue to function past 5 years. In addition, clinical trials are in progress to determine visual improvements in patients implanted with subretinal devices of similar design [19], while animal studies are addressing the mechanisms behind these improvements [24,32]. Ultimately, biocompatibility, durability, and efficacy will all be necessary components of a viable visual prosthetic for the treatment of RP.…”

Section: Discussionmentioning

confidence: 99%

“…Since the MPA device is designed for patients with RP, the loss of photoreceptors overlying the implant does not exclude the use of this device in these patients. Additionally, studies with the Royal College of Surgeons rat model of RP indicate no changes in the inner retina 8 weeks after implantation [32].…”

Section: Retinal Structurementioning

confidence: 99%

Status of the feline retina 5 years after subretinal implantation

Pardue

Ball

Phillips³

et al. 2006

JRRD

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Abstract-Retinal prosthetics are designed to restore functional vision to patients with photoreceptor degeneration by detecting light and stimulating the retina. Since devices are surgically implanted into the eye, long-term biocompatibility and durability are critical for viable treatment of retinal disease. To extend our previous work, which demonstrated the biocompatibility of a microphotodiode array (MPA) for 10 to 27 months in the normal feline retina, we implanted normal cats with an MPA implant backed with either an iridium oxide or platinum electrode and examined retinal function and biocompatibility for 3 to 5 years. All implants functioned throughout the study period. Retinal function remained steady and normal with a less than 15 percent decrease in electroretinogram response. The retinas had normal laminar structure with no signs of inflammation or rejection in areas adjacent to or distant from the implants. Directly over the implants, a loss of photoreceptor nuclei and remodeling of inner retinal layers existed. These results indicate that the subretinal MPA device is durable and well tolerated by the retina 5 years postimplantation.

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“…21,28,66 Interestingly, histological analysis showed a significant increase in photoreceptors at the implant location when compared with sham-operated or non-operated eyes. 28 Analysis of the response at the superior colliculus revealed activity that matched where the implant was positioned in the retina 66 highlighting the visual pathway response from this retinal circuitry.…”

Section: Integrity Of the Neural Retina Following Stimulationmentioning

confidence: 97%

“…Follow-up studies in animal models indicate that implantation of an artificial silicon retina induces release of growth factors that have a beneficial effect on the surrounding retina. 21,[26][27][28] The use of microphotodiodes to generate light-induced current has been adopted successfully by a German group, Retina Implant AG. 23 Their device consists of 1,500 microphotodiodes arranged in a 38 by 40 grid.…”

Section: Microphotodiode-based Implantsmentioning

confidence: 99%