Transplant of Full-Thickness Embryonic Rabbit Retina Using Pars Plana Vitrectomy

Ghosh, Fredrik; Arnér, Karin; Ehinger, Berndt

doi:10.1097/00006982-199818020-00007

Cited by 45 publications

(42 citation statements)

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“…The relatively atraumatic delivery technique with a very slow injection rate may also be an important factor in the good morphology observed in many of the grafts. Certainly, numerous previous studies of transplantation of intact fetal retinal sheets has demonstrated that minimization of surgical trauma is a critical factor in the achievement of laminated transplants and reducing rosette formation (Aramant et al, 1999;Ghosh et al, 1998). In our study, no rosettes were observed following subretinal transplantation of RPCs.…”

Section: Discussionsupporting

confidence: 42%

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats

Qiu

Seiler

Mui

et al. 2005

Experimental Eye Research

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Previous studies evaluating neural stem cells transplanted into the mature retina have demonstrated limited levels of graft-host integration and photoreceptor differentiation. The purpose of this investigation is to enhance photoreceptor cell differentiation and integration of retinal progenitor cells (RPC) following subretinal transplantation into retinal degenerate rats by optimization of isolation, expansion, and transplantation procedures.RPCs were isolated from human placental alkaline phosphatase (hPAP)-positive embryonic day 17 (E17) rat retina and expanded in serum-free defined media. RPCs at passage 2 underwent in vitro induction with all trans retinoic acid or were transplanted into the subretinal space of post-natal day (P) 17 S334ter-3 and S334ter-5 transgenic rats. Animals were examined post-operatively by ophthalmoscopy and optical coherence tomography (OCT) at weeks 1 and 4. Differentiation profiles of RPCs, both in vitro and in vivo were analysed microscopically by immunohistochemistry for various retinal cell specific markers. Our results demonstrated that the majority of passage 2 RPCs differentiated into retina-specific neurons expressing rhodopsin after in vitro induction. Following subretinal transplantation, grafted cells formed a multi-layer cellular sheet in the subretinal space in both S334ter-3 and S334ter-5 rats. Prominent retina-specific neuronal differentiation was observed in both rat lines as evidenced by recoverin or rhodopsin staining in 80% of grafted cells. Less than 5% of the grafted cells expressed glial fibrillary acidic protein. Synapsin-1 (label for nerve terminals) positive neural processes were present at the graft-host interface. Expression profiles of the grafted RPCs were similar to those of RPCs induced to differentiate in vitro using all-trans retinoic acid.In contrast to our previous study, grafted RPCs can demonstrate extensive rhodopsin expression, organize into layers, and show some features of apparent integration with the host retina following subretinal transplantation in slow and fast retinal degenerate rats. The similarity of the in vitro and in vivo RPC differentiation profiles suggests that intrinsic signals may have a significant contribution to RPC cell fate determination. q

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Section: Discussionsupporting

confidence: 42%

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats

Qiu

Seiler

Mui

et al. 2005

Experimental Eye Research

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“…This phenomenon, indicating abnormal growth of the graft along the scleral-vitreal axis, has not been found in eyes transplanted with neonatal or adult donor tissue [16,31], but has been noted in short-term fetal rabbit grafts [11]. Evidently, the confined space in the subretinal space does not allow lateral expansion of the graft, which would be more desirable.…”

Section: Graft-host Integrationmentioning

confidence: 96%

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

Ghosh

Engelsberg

English

et al. 2006

Graefe's Arch Clin Exp Ophthalmol

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Purpose: To explore neuroretinal transplantation in a large-animal model of severe retinitis pigmentosa, and to establish graft development, long-term survival, graft-host integration and effects on the host retina.Methods: Rhodopsin transgenic pigs, aged 6 months, in 1 eye received a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope, and with immunohistochemical markers. Full-field ERG was performed at 4 and 6 months.Results: Laminated grafts with well organized photoreceptors, rod bipolar cells and Müller cells were found in 5 out of 6 eyes. Neuronal connections between graft and host retina were not seen. In the 5 eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions:Fetal full-thickness neuroretina can be transplanted safely to an eye with a severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma but the presence of a well laminated graft counteracts this effect and rescues rods from degeneration.

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“…Since then, many investigators have reported encouraging results in this difficult field in animal models (Silverman and Hughes, 1989;del Cerro et al, 1991;Silverman et al, 1992;Gouras et al, 1994;Ghosh et al, 1998;Seiler and Aramant, 1998;Aramant et al, 1999;Kwan et al, 1999;Gouras and Tanabe, 2003) and in human patients (Das et al, 1999;Radtke et al, 1999;del Cerro et al, 2000;Humayun et al, 2000;Radtke et al, 2002;Radtke et al, 2004). Several studies have suggested some improvement in visual function as judged from light reflexes, behavioral testing, and electrophysiological responses in blind animal models (del Cerro et al, 1991;Silverman et al, 1992;del Cerro et al, 1995;Kwan et al, 1999;Radner et al, 2001;Woch et al, 2001;Sagdullaev et al, 2003;Thomas et al, 2004).…”

mentioning

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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Transplant of Full-Thickness Embryonic Rabbit Retina Using Pars Plana Vitrectomy

Cited by 45 publications

References 0 publications

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

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

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