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Transplantation of photoreceptor and total neural retina preserves cone function in P23H rhodopsin transgenic rat.

Yang Y, Mohand-Said S, Léveillard T, Fontaine V, Simonutti M, Sahel JA - PLoS ONE (2010)

Bottom Line: We present evidence for an alternative strategy aimed at preventing the secondary loss of cones, the most crucial photoreceptors for vision, by transplanting normal photoreceptors cells into the eye of the P23H rat, a model of dominant retinitis pigmentosa.In both groups, cone loss was significantly reduced (10%) in the transplanted eyes where the cone outer segments were found to be considerably longer.We demonstrate here that the transplanted tissue prevents the loss of cone function, which is further translated into cone survival.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U968, Paris, France.

ABSTRACT

Background: Transplantation as a therapeutic strategy for inherited retinal degeneration has been historically viewed to restore vision as a method by replacing the lost retinal cells and attempting to reconstruct the neural circuitry with stem cells, progenitor cells and mature neural retinal cells.

Methods and findings: We present evidence for an alternative strategy aimed at preventing the secondary loss of cones, the most crucial photoreceptors for vision, by transplanting normal photoreceptors cells into the eye of the P23H rat, a model of dominant retinitis pigmentosa. We carried out transplantation of photoreceptors or total neural retina in 3-month-old P23H rats and evaluated the function and cell counts 6 months after surgery. In both groups, cone loss was significantly reduced (10%) in the transplanted eyes where the cone outer segments were found to be considerably longer. This morphological effect correlated with maintenance of the visual function of cones as scored by photopic ERG recording, but more precisely with an increase in the photopic b-wave amplitudes by 100% and 78% for photoreceptor transplantation and whole retinal transplantation respectively.

Conclusions: We demonstrate here that the transplanted tissue prevents the loss of cone function, which is further translated into cone survival.

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Related in: MedlinePlus

Effect of transplantation to P23H retinas at 9 months of age.(A) Immunolabeling of the flat-mounted degenerating retina (Rho-4D2 antibody, red) with retinal transplant. Due to degeneration, almost no rods were detected except the transplant in the dorsal host retina. Images1 and 2 were taken respectively in the nasal-ventral, temporal-ventral quadrants, both far from and opposite to the transplant. D: dorsal, V: ventral, N: nasal, T: temporal, PNA lectin: green, Rho-4D2 antibody: red. (B) Immunolabeling of cones with PNA lectin in the control and photoreceptor transplanted retinas from the same animal. The two images were taken in the same areas from the nasal-ventral quadrant, showing that cone outer segments are longer in the transplanted retina than in the control retina.
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pone-0013469-g002: Effect of transplantation to P23H retinas at 9 months of age.(A) Immunolabeling of the flat-mounted degenerating retina (Rho-4D2 antibody, red) with retinal transplant. Due to degeneration, almost no rods were detected except the transplant in the dorsal host retina. Images1 and 2 were taken respectively in the nasal-ventral, temporal-ventral quadrants, both far from and opposite to the transplant. D: dorsal, V: ventral, N: nasal, T: temporal, PNA lectin: green, Rho-4D2 antibody: red. (B) Immunolabeling of cones with PNA lectin in the control and photoreceptor transplanted retinas from the same animal. The two images were taken in the same areas from the nasal-ventral quadrant, showing that cone outer segments are longer in the transplanted retina than in the control retina.

Mentions: In the present study, a piece of normal retinal tissue from Sprague Dawley rat (SD) containing either isolated photoreceptors (97% rods) or whole neural retina was transplanted into 3 month-old P23H rat by subretinal insertion. Fundus examination carried out immediately after transplantation revealed retinal detachment induced by the surgery at the site where the graft was placed beneath the neural retina (RD, Figure 1A). One week after transplantation, the retinal detachment had healed as seen in the fundus of the treated eye (Figure 1B) which does not differ from the fellow eye (Figure 1C). Two months after transplantation, fundus fluorescence imaging was performed to visualize the transplant. Only natural autofluorescence can be observed in the fundus of non-transplanted eyes (Figure 1D). However, the transplant (labeled with the fluorescent dye PKH26) was indicated by the hyper autofluorescence, situated in a zone superior to the optic nerve (ON, Figure 1E) in the transplanted eyes. The P23H rats (transplanted at 3 months of age) were sacrificed 6 months later for scoring the survival effect on cones. In transversal sections of the retina (6 months post-transplantation) the presence of the transplant can be detected by anti-rhodopsin antibody staining (green) since the rods of the host animal have degenerated, showing that the transplant is apposed to the inner nuclear layer of the host retina stained in blue with DAPI (Figure 1F). On the flat mounted P23H retina, the grafted tissue was visualized in the upper part of Figure 2A by anti-rhodopsin antibody labeling (red). In both series (whole retina and photoreceptor transplantations) grafts were detected in 100% of the operated eyes, covering less than ¼ of the retinal surface.


Transplantation of photoreceptor and total neural retina preserves cone function in P23H rhodopsin transgenic rat.

Yang Y, Mohand-Said S, Léveillard T, Fontaine V, Simonutti M, Sahel JA - PLoS ONE (2010)

Effect of transplantation to P23H retinas at 9 months of age.(A) Immunolabeling of the flat-mounted degenerating retina (Rho-4D2 antibody, red) with retinal transplant. Due to degeneration, almost no rods were detected except the transplant in the dorsal host retina. Images1 and 2 were taken respectively in the nasal-ventral, temporal-ventral quadrants, both far from and opposite to the transplant. D: dorsal, V: ventral, N: nasal, T: temporal, PNA lectin: green, Rho-4D2 antibody: red. (B) Immunolabeling of cones with PNA lectin in the control and photoreceptor transplanted retinas from the same animal. The two images were taken in the same areas from the nasal-ventral quadrant, showing that cone outer segments are longer in the transplanted retina than in the control retina.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957406&req=5

pone-0013469-g002: Effect of transplantation to P23H retinas at 9 months of age.(A) Immunolabeling of the flat-mounted degenerating retina (Rho-4D2 antibody, red) with retinal transplant. Due to degeneration, almost no rods were detected except the transplant in the dorsal host retina. Images1 and 2 were taken respectively in the nasal-ventral, temporal-ventral quadrants, both far from and opposite to the transplant. D: dorsal, V: ventral, N: nasal, T: temporal, PNA lectin: green, Rho-4D2 antibody: red. (B) Immunolabeling of cones with PNA lectin in the control and photoreceptor transplanted retinas from the same animal. The two images were taken in the same areas from the nasal-ventral quadrant, showing that cone outer segments are longer in the transplanted retina than in the control retina.
Mentions: In the present study, a piece of normal retinal tissue from Sprague Dawley rat (SD) containing either isolated photoreceptors (97% rods) or whole neural retina was transplanted into 3 month-old P23H rat by subretinal insertion. Fundus examination carried out immediately after transplantation revealed retinal detachment induced by the surgery at the site where the graft was placed beneath the neural retina (RD, Figure 1A). One week after transplantation, the retinal detachment had healed as seen in the fundus of the treated eye (Figure 1B) which does not differ from the fellow eye (Figure 1C). Two months after transplantation, fundus fluorescence imaging was performed to visualize the transplant. Only natural autofluorescence can be observed in the fundus of non-transplanted eyes (Figure 1D). However, the transplant (labeled with the fluorescent dye PKH26) was indicated by the hyper autofluorescence, situated in a zone superior to the optic nerve (ON, Figure 1E) in the transplanted eyes. The P23H rats (transplanted at 3 months of age) were sacrificed 6 months later for scoring the survival effect on cones. In transversal sections of the retina (6 months post-transplantation) the presence of the transplant can be detected by anti-rhodopsin antibody staining (green) since the rods of the host animal have degenerated, showing that the transplant is apposed to the inner nuclear layer of the host retina stained in blue with DAPI (Figure 1F). On the flat mounted P23H retina, the grafted tissue was visualized in the upper part of Figure 2A by anti-rhodopsin antibody labeling (red). In both series (whole retina and photoreceptor transplantations) grafts were detected in 100% of the operated eyes, covering less than ¼ of the retinal surface.

Bottom Line: We present evidence for an alternative strategy aimed at preventing the secondary loss of cones, the most crucial photoreceptors for vision, by transplanting normal photoreceptors cells into the eye of the P23H rat, a model of dominant retinitis pigmentosa.In both groups, cone loss was significantly reduced (10%) in the transplanted eyes where the cone outer segments were found to be considerably longer.We demonstrate here that the transplanted tissue prevents the loss of cone function, which is further translated into cone survival.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U968, Paris, France.

ABSTRACT

Background: Transplantation as a therapeutic strategy for inherited retinal degeneration has been historically viewed to restore vision as a method by replacing the lost retinal cells and attempting to reconstruct the neural circuitry with stem cells, progenitor cells and mature neural retinal cells.

Methods and findings: We present evidence for an alternative strategy aimed at preventing the secondary loss of cones, the most crucial photoreceptors for vision, by transplanting normal photoreceptors cells into the eye of the P23H rat, a model of dominant retinitis pigmentosa. We carried out transplantation of photoreceptors or total neural retina in 3-month-old P23H rats and evaluated the function and cell counts 6 months after surgery. In both groups, cone loss was significantly reduced (10%) in the transplanted eyes where the cone outer segments were found to be considerably longer. This morphological effect correlated with maintenance of the visual function of cones as scored by photopic ERG recording, but more precisely with an increase in the photopic b-wave amplitudes by 100% and 78% for photoreceptor transplantation and whole retinal transplantation respectively.

Conclusions: We demonstrate here that the transplanted tissue prevents the loss of cone function, which is further translated into cone survival.

Show MeSH
Related in: MedlinePlus