Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model<i>in vivo</i>

Fransen, James W.; Pangeni, Gobinda; Pardue, Machelle T.; McCall, Maureen A.

doi:10.1088/1741-2560/11/4/046012

Cited by 11 publications

(20 citation statements)

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“…We also assessed glial reaction in tissues within and distal to the implant site from 16 to 26 weeks post implantation in the S334ter-3 and 4 weeks post implantation in the RCS rat. Our results suggest that both the mPVA and bPVA designs are well tolerated and preserve the necessary inner retinal circuitry that underlie the transmission of signals to the RGCs and beyond (Fransen et al, 2014). …”

Section: Introductionmentioning

confidence: 77%

“…Monocular implantation accommodated superior colliculus recordings that are reported elsewhere (Fransen et al, 2014). The S334ter-3 is a rapid degeneration model and most photoreceptors had degenerated at the time of implantation (McGill et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

“…Each pixel contains an active electrode in its center and a return electrode at the circumference. Upon illumination with a pulse of light, each pixel generates a biphasic pulse of electric current flowing through the tissue between electrodes, primarily stimulating the inner nuclear layer (INL) cells (Fransen et al, 2014). Electrodes were coated in iridium oxide and the details of manufacturing methods of the bPVA were published previously (Wang et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

“…Subretinally placed photovoltaic arrays (PVAs) provide targeted stimulation to the inner nuclear layer (INL) (Fransen et al, 2014) due to their current density distribution and size (Mathieson et al 2012). Because bipolar cells are interneurons that connect photoreceptors to RGCs they are involved in signal transmission with PVAs.…”

Section: Introductionmentioning

confidence: 99%

“…The bPVA gaps enhance proximity of the electrodes to inner retinal neurons and allow diffusion of extracellular milieu through the implant (Adkins et al, 2013; Mathieson et al, 2012). Since the subretinal PVA stimulates retinal neurons that are within close proximity to the electrode (Fransen et al, 2014), we focused our analysis on inner retinal cells that are likely activated by the PVA device. Rod bipolar cells and cholinergic amacrine cells represent well defined populations of cells with robust cellular markers to assess overall inner retinal health.…”

Section: Introductionmentioning

confidence: 99%

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Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

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Fransen

Adekunle

et al. 2014

Experimental Eye Research

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Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6 to 12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16 to 26 weeks post implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission.

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Section: Introductionmentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Light

Fransen

Adekunle

et al. 2014

Experimental Eye Research

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Characterization of a Polymer‐Based, Fully Organic Prosthesis for Implantation into the Subretinal Space of the Rat

Antognazza

Paolo

Ghezzi

et al. 2016

Adv Healthcare Materials

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Replacement strategies arise as promising approaches in case of inherited retinal dystrophies leading to blindness. A fully organic retinal prosthesis made of conjugated polymers layered onto a silk fibroin substrate is engineered. First, the biophysical and surface properties are characterized; then, the long-term biocompatibility is assessed after implantation of the organic device in the subretinal space of 3-months-old rats for a period of five months. The results indicate a good stability of the subretinal implants over time, with preservation of the physical properties of the polymeric layer and a tight contact with the outer retina. Immunoinflammatory markers detect only a modest tissue reaction to the surgical insult and the foreign body that peaks shortly after surgery and progressively decreases with time to normal levels at five months after implantation. Importantly, the integrity of the polymeric layer in direct contact with the retinal tissue is preserved after five months of implantation. The recovery of the foreign-body tissue reaction is also associated with a normal b-wave in the electroretinographic response. The results demonstrate that the device implanted in nondystrophic eyes is well tolerated, highly biocompatible, and suitable as retinal prosthesis in case of photoreceptor degeneration.

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Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration

LaVail

Nishikawa

Steinberg

et al. 2018

Experimental Eye Research

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We produced 8 lines of transgenic (Tg) rats expressing one of two different rhodopsin mutations in albino Sprague-Dawley (SD) rats. Three lines were generated with a proline to histidine substitution at codon 23 (P23H), the most common autosomal dominant form of retinitis pigmentosa in the United States. Five lines were generated with a termination codon at position 334 (S334ter), resulting in a C-terminal truncated opsin protein lacking the last 15 amino acid residues and containing all of the phosphorylation sites involved in rhodopsin deactivation, as well as the terminal QVAPA residues important for rhodopsin deactivation and trafficking. The rates of photoreceptor (PR) degeneration in these models vary in proportion to the ratio of mutant to wild-type rhodopsin. The models have been widely studied, but many aspects of their phenotypes have not been described. Here we present a comprehensive study of the 8 Tg lines, including the time course of PR degeneration from the onset to one year of age, retinal structure by light and electron microscopy (EM), hemispheric asymmetry and gradients of rod and cone degeneration, rhodopsin content, gene dosage effect, rapid activation and invasion of the outer retina by presumptive microglia, rod outer segment disc shedding and phagocytosis by the retinal pigmented epithelium (RPE), and retinal function by the electroretinogram (ERG). The biphasic nature of PR cell death was noted, as was the lack of an injury-induced protective response in the rat models. EM analysis revealed the accumulation of submicron vesicular structures in the interphotoreceptor space during the peak period of PR outer segment degeneration in the S334ter lines. This is likely due to the elimination of the trafficking consensus domain as seen before as with other rhodopsin mutants lacking the C-terminal QVAPA. The 8 rhodopsin Tg lines have been, and will continue to be, extremely useful models for the experimental study of inherited retinal degenerations.

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Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa modelin vivo

Cited by 11 publications

References 50 publications

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Characterization of a Polymer‐Based, Fully Organic Prosthesis for Implantation into the Subretinal Space of the Rat

Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration

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