Limitation of Anatomical Integration between Subretinal Transplants and the Host Retina

Zhang, Yiqin; Arnér, Karin; Ehinger, Berndt; Perez, Maria–Thereza R.

doi:10.1167/iovs.02-0132

Cited by 49 publications

(40 citation statements)

References 28 publications

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“…Instead of trying to increase neuronal survival, we for the current experiment, wanted to use the explant system to instead specifically enhance photoreceptor cell death with the prospect of removing diseased cells within a future fullthickness transplantation paradigm. In this setting, a tissue engineering intervention in which diseased photoreceptors are removed in the diseased host without damage to the inner retina would increase the possibility of graft-host connectivity (Ghosh et al, 1999;Zhang et al, 2003). From our results, adding insult to injury, i. e MNU treatment of adult retina in vitro, results in incomplete removal of photoreceptors with concomitant significant death of horizontal and rod bipolar cells.…”

Section: Discussionmentioning

confidence: 75%

“…However, to restore visual function in a diseased eye, grafted photoreceptors also need to form synaptic connections with host inner retinal cells, a phenomenon which is hampered by remaining host photoreceptor and reactive glial cells even in severely degenerated retinas (Ghosh et al, 2007;Wanner et al, 2008). Interestingly, neuronal integration has been demonstrated if the outer retina of the host is disrupted mechanically or by ischemia, indicating that selective removal of photoreceptors prior to transplantation may be required for successful fusion of graft-host neurons (Ghosh et al, 1999;Zhang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N-methyl-N-nitrosourea-induced neuronal cell death in a large animal model of retinal degeneration in vitro

Taylor

Arnér

Ghosh

2016

Experimental Eye Research

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

N-methyl-N-nitrosourea-induced neuronal cell death in a large animal model of retinal degeneration in vitro

Taylor

Arnér

Ghosh

2016

Experimental Eye Research

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“…The first mechanism is direct replacement of the damaged retina and reestablishment of functional neural connections with the remaining host retina. Although there is evidence that transplants themselves are functional (Adolph et al, 1994;Seiler et al, 1999) and that some degree of graft-host integration can occur after retinal transplantation (Ehinger et al, 1991;Silverman et al, 1992;Gouras et al, 1994;Aramant and Seiler, 1995;Seiler and Aramant, 1998;Ghosh et al, 1999;Kwan et al, 1999;Gouras and Tanabe, 2003;Zhang et al, 2003), the presence of definite functional synaptic connections has not yet been reported. As a second potential mechanism of action, the transplanted tissue could provide an indirect effect via the release of humoral factors that could prevent or retard the degeneration of the remaining host photoreceptors (Mohand-Said et al, 1997, 2000Fintz et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Restoration of visual responses following transplantation of intact retinal sheets in rd mice

Arai

Thomas

Seiler

et al. 2004

Experimental Eye Research

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Purpose. To correlate the functional outcomes with histologic findings following transplantation of fetal retinal sheets in rd mice, and to investigate the mechanisms of visual function restoration.Methods. Twenty-one postnatal day 31 -38 rd/rd (C3H/HeJ) mice were transplanted in one eye with retinal sheets (1·0 £ 0·4 mm) obtained from embryonic day (E) 17 enhanced-green-fluorescent protein (eGFP) mice. Five mice underwent sham surgery without insertion of tissue. Four to five weeks after transplantation, visual responses to a light flash were recorded across the superior colliculus (SC) in seven eyes of seven transplanted mice that had clear corneas and lenses, and in all five sham surgery mice. Following the SC recording, the eyes were enucleated and processed for immunohistochemistry and examined using confocal microscopy.Results. In three out of the seven eyes (43%), positive responses were recorded in the SC in an area topographically corresponding to the placement of the transplant in the host retina. No responses were recorded in the untreated eyes of 5-week-old and 9-week-old rd/rd mice, and in the 9-week-old sham surgery mice. In contrast, visual responses were recorded over the entire SC in normal eyes. The response onset latencies of the 3 transplanted mice with responses were similar to those of normal control mice. The organization of the graft did not appear to correlate as expected with the electrophysiology results, as eyes with well-organized, laminated grafts showed no response whereas the three light-responsive eyes had rosetted or disorganized grafts. All three light-responsive eyes demonstrated much higher levels of recoverin immunoreactivity in the host retina overlying the graft compared with untreated age-matched rd/rd mice.Conclusion. Restoration of the SC visual response does not appear to depend on a well-organized transplant in the rd mouse. Increased recoverin-staining in the host retina in light-responsive animals suggested that host cone rescue was the likely mechanism of vision restoration in this transplant model. q

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“…Graft-host integration has been shown sporadically in cases where host photoreceptors are absent, indicating that removal of these cells before actual transplantation may be important. 3,4 Prolonged separation of the neuroretina from the retinal pigment epithelium (RPE), retinal detachment, leads to degeneration of photoreceptors due to diminished nutritive support from the choroid. 5 For the present experiment, we wanted to investigate if photoreceptors can be removed by temporary retinal detachment induced by a biodegradable membrane, poly(glycerol sebacate) (PGS), placed in the subretinal space.…”

mentioning

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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Limitation of Anatomical Integration between Subretinal Transplants and the Host Retina

Abstract: The present study demonstrates that the host photoreceptor layer plays a role in limiting graft-host anatomical integration.

Cited by 49 publications

References 28 publications

N-methyl-N-nitrosourea-induced neuronal cell death in a large animal model of retinal degeneration in vitro

N-methyl-N-nitrosourea-induced neuronal cell death in a large animal model of retinal degeneration in vitro

Restoration of visual responses following transplantation of intact retinal sheets in rd mice

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

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