Status of the feline retina 5 years after subretinal implantation

Pardue, Machelle T.; Ball, Sherry L.; Phillips, M.; Faulkner, Amanda E.; Walker, Tiffany; Chow, Alan Y.; Peachey, Neal S.

doi:10.1682/jrrd.2005.07.0118

Cited by 26 publications

(13 citation statements)

References 26 publications

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“…Late stage interventions will need to circumvent the consequences of both gliosis and the remodeling that occurs in second order neurons. Early intervention will also be key for retinal prosthetic approaches (Jensen and Rizzo, 2006; Pardue et al, 2006; Besch et al, 2008; Pardue et al, 2008; Butterwick et al, 2009), in order to take advantage of the high degree of preservation of retinal circuits at the level of the inner retina which our data and others (Mazzoni et al, 2008) suggest remains largely intact in the retinas of the rd10 mouse model of RP , even following extended photoreceptor degeneration.…”

Section: Discussionmentioning

confidence: 84%

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa

Phillips

Otteson

Sherry

2010

J of Comparative Neurology

101

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The Pde6b rd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second-and third-order retinal cells and their synaptic terminals in retinas from Pde6b rd10 (rd10)mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell-and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby secondorder neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5.

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Section: Discussionmentioning

confidence: 84%

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa

Phillips

Otteson

Sherry

2010

J of Comparative Neurology

101

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“…There are various types of visual prostheses, and according to the locations that are stimulated, they can be generally divided into the following categories: epiretinal, 1,3,[19][20][21][22] subretinal, 2,8,13,[23][24][25] suprachoroidal, 4,15,26,27 intrapapillary, 28 extraocular, 12 thalamic, 7 cortical, 6,10,11 and optic nerve (ON). 5,14 Among them, the ON approach may potentially achieve artificial vision over a relatively large area of the visual field.…”

Section: Resultsmentioning

confidence: 99%

Electrically Evoked Responses in the Rabbit Cortex Induced by Current Steering With Penetrating Optic Nerve Electrodes

Yan

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Current steering is a neural stimulation strategy that uses simultaneous stimulation of adjacent electrodes to produce additional intermediate stimulation sites and thus improves spatial resolution. We investigated the feasibility of current steering using electrophysiological and computational methods after implanting paired penetrating electrodes into the rabbit's optic nerve (ON). METHODS.Penetrating electrodes at different interelectrode distances were implanted into the ON and electrically evoked cortical potentials (EEPs) in V1 recorded with a 6 3 8 array. The current thresholds, EEP amplitudes, and spatial distributions were analyzed during current steering. Computational simulation studies were performed based on finite element models to calculate the area and spatial distribution of recruited ON fibers using a current steering stimulation strategy. RESULTS.Threshold reduction and EEP amplitude enhancement were found with simultaneous stimulation of closely spaced electrode pairs. Spatially shifted cortical responses were achieved using current steering, whereas the amplitudes and spatial spreads of the responses were similar to that elicited by a single electrode. Computational simulations suggested that the centroid of the ON recruitment area could be modulated by current steering while the total recruitment area did not show any appreciable variability at a fixed current intensity.CONCLUSIONS. Current steering is a useful strategy to enhance the spatial resolution of an ON prosthesis without increasing the number of physical electrodes. This study provides useful information for optimizing the design of stimulation strategies with a penetrating ON prosthesis.

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“…A previous study on the biocompatibility of a nondegradable subretinal prosthetic reported unintended photoreceptor degeneration. 27 Presumably, the prosthetic blocked the flow of nutrients from the choroid=RPE to the photoreceptor layer leading to the observed degeneration.…”

Section: Discussionmentioning

confidence: 99%

Selective Removal of Photoreceptor CellsIn VivoUsing the Biodegradable Elastomer Poly(Glycerol Sebacate)

Ghosh

Neeley

Arnér

et al. 2011

Tissue Engineering Part A

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Retinal transplantation experiments have advanced considerably during recent years, but remaining diseased photoreceptor cells in the host retina physically obstruct the development of graft-host neuronal contacts that are required for vision. We here report selective removal of photoreceptors using the biodegradable elastomer poly(glycerol sebacate) (PGS). A 1Â3 mm PGS membrane was implanted in the subretinal space of normal rabbit eyes, and morphologic specimens were examined with hematoxylin and eosin staining and a panel of immunohistochemical markers. Seven days postoperatively, a patent separation of the neuroretina and retinal pigment epithelium was found as well as loss of several rows of photoreceptors in combination with massive terminal transferase-mediated dUTP nick-end labeling (TUNEL) staining for apoptosis in the outer nuclear layer. After 28 days, the neuroretina was reattached, the PGS membrane had degraded, and photoreceptors were absent in the implantation area. Activated Mü ller cells were found in the entire retina in 7-day specimens, and in the implantation area after 28 days. AII amacrine and rod bipolar cell morphology was not affected, except for disrupted dendritic branching, which was present in rod bipolar cells in 28-day specimens. We conclude that retinal detachment induced by the biodegradable PGS membrane creates a permissive environment in which graft-host neuronal connections may be facilitated in future retinal transplantation experiments.

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Status of the feline retina 5 years after subretinal implantation

Cited by 26 publications

References 26 publications

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa

Electrically Evoked Responses in the Rabbit Cortex Induced by Current Steering With Penetrating Optic Nerve Electrodes

Selective Removal of Photoreceptor CellsIn VivoUsing the Biodegradable Elastomer Poly(Glycerol Sebacate)

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