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Assessment of the innate and adaptive immune system in proliferative vitreoretinopathy.

Zhang W, Tan J, Liu Y, Li W, Gao Q, Lehmann PV - Eye (Lond) (2012)

Bottom Line: Additionally, immunofluorescence analysis was performed.Carboxyfluorescein diacetate succinimidyl ester-labeled T cells that are specific for ovalbumin were detected in the inflamed vitreous and retina showing that T cells that are not specific for autoantigens present in the eye can migrate to PVR lesions.This study suggests that T- and B-cell immunity is not essential for the induction of PVR.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

ABSTRACT

Purpose: Proliferative vitreoretinopathy (PVR) is the leading cause of failure of surgery for rhegmatogenous retinal detachment. Although indirect evidence suggests that this disease might be autoimmune in nature, direct proof for this hypothesis is lacking. The purpose of this study was to determine in a murine model whether PVR can develop in the absence of T- or B-cell immunity.

Methods: Four- to six-week-old Rag-1 gene knockout (KO) and congenic wild-type mice (WT) on the C57.Bl/6 background were studied. PVR was induced by intravitreal injection of 3 μl dispase at the concentration of 0.2 U/μl. PVR development was monitored by electroretinograms, the macroscopic observation of hemorrhage, cataract, retinal folds, and of an uneven iris, as well as the histological detection of epiretinal membranes on haematoxylin-eosin stained tissue. Additionally, immunofluorescence analysis was performed. These manifestations of PVR were assessed 1, 2, 4, 6, and 8 weeks after the intravitreal injection.

Results: The data showed that the immune-deficient Rag-1 KO mice developed PVR with similar kinetics and severity as did the fully immune competent congenic WT mice. Carboxyfluorescein diacetate succinimidyl ester-labeled T cells that are specific for ovalbumin were detected in the inflamed vitreous and retina showing that T cells that are not specific for autoantigens present in the eye can migrate to PVR lesions. Therefore, the mere presence of T cells in PVR lesions does not imply an autoimmune pathogenesis.

Conclusion: This study suggests that T- and B-cell immunity is not essential for the induction of PVR.

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Related in: MedlinePlus

Rag-1 KO mice develop all cardinal features of PVR. Representative PVR manifestations are shown for a total of 45 Rag-1 KO mice studied 2–8 weeks after injection of dispase. (a) Traction membrane in dispase-injected eye as indicated by arrow. (b) Proliferative membrane in vitreal cavity and retinal detachment as indicated by arrow. (c) Immunofluorescence staining for α-SMA (c-1), GFAP (c-2), GS (c-5), and RPE-65 (c-6) in the epiretinal membrane (EM), and Hoechst 33342 staining to mark cell nuclei with the EM (c-3 and c-7). c-4 is the merged picture of c-1–c-3, and c-8 is the merged picture of c-5–c-7 (triple staining).
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fig1: Rag-1 KO mice develop all cardinal features of PVR. Representative PVR manifestations are shown for a total of 45 Rag-1 KO mice studied 2–8 weeks after injection of dispase. (a) Traction membrane in dispase-injected eye as indicated by arrow. (b) Proliferative membrane in vitreal cavity and retinal detachment as indicated by arrow. (c) Immunofluorescence staining for α-SMA (c-1), GFAP (c-2), GS (c-5), and RPE-65 (c-6) in the epiretinal membrane (EM), and Hoechst 33342 staining to mark cell nuclei with the EM (c-3 and c-7). c-4 is the merged picture of c-1–c-3, and c-8 is the merged picture of c-5–c-7 (triple staining).

Mentions: Figure 1 shows that immune-deficient Rag-1 KO mice develop all cardinal features of PVR after intravitreal injection of dispase (Figure 1a). Formation of marked EMs and tractional retinal detachment was seen in the vitreous cavity (Figure 1b). In the EM cells, characteristic of PVR were detected, namely glial cells, fibroblasts, RPE-, and Mûller cells staining for GFAP, α-SMA, RPE65, and GS, respectively (Figure 1c).


Assessment of the innate and adaptive immune system in proliferative vitreoretinopathy.

Zhang W, Tan J, Liu Y, Li W, Gao Q, Lehmann PV - Eye (Lond) (2012)

Rag-1 KO mice develop all cardinal features of PVR. Representative PVR manifestations are shown for a total of 45 Rag-1 KO mice studied 2–8 weeks after injection of dispase. (a) Traction membrane in dispase-injected eye as indicated by arrow. (b) Proliferative membrane in vitreal cavity and retinal detachment as indicated by arrow. (c) Immunofluorescence staining for α-SMA (c-1), GFAP (c-2), GS (c-5), and RPE-65 (c-6) in the epiretinal membrane (EM), and Hoechst 33342 staining to mark cell nuclei with the EM (c-3 and c-7). c-4 is the merged picture of c-1–c-3, and c-8 is the merged picture of c-5–c-7 (triple staining).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376296&req=5

fig1: Rag-1 KO mice develop all cardinal features of PVR. Representative PVR manifestations are shown for a total of 45 Rag-1 KO mice studied 2–8 weeks after injection of dispase. (a) Traction membrane in dispase-injected eye as indicated by arrow. (b) Proliferative membrane in vitreal cavity and retinal detachment as indicated by arrow. (c) Immunofluorescence staining for α-SMA (c-1), GFAP (c-2), GS (c-5), and RPE-65 (c-6) in the epiretinal membrane (EM), and Hoechst 33342 staining to mark cell nuclei with the EM (c-3 and c-7). c-4 is the merged picture of c-1–c-3, and c-8 is the merged picture of c-5–c-7 (triple staining).
Mentions: Figure 1 shows that immune-deficient Rag-1 KO mice develop all cardinal features of PVR after intravitreal injection of dispase (Figure 1a). Formation of marked EMs and tractional retinal detachment was seen in the vitreous cavity (Figure 1b). In the EM cells, characteristic of PVR were detected, namely glial cells, fibroblasts, RPE-, and Mûller cells staining for GFAP, α-SMA, RPE65, and GS, respectively (Figure 1c).

Bottom Line: Additionally, immunofluorescence analysis was performed.Carboxyfluorescein diacetate succinimidyl ester-labeled T cells that are specific for ovalbumin were detected in the inflamed vitreous and retina showing that T cells that are not specific for autoantigens present in the eye can migrate to PVR lesions.This study suggests that T- and B-cell immunity is not essential for the induction of PVR.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

ABSTRACT

Purpose: Proliferative vitreoretinopathy (PVR) is the leading cause of failure of surgery for rhegmatogenous retinal detachment. Although indirect evidence suggests that this disease might be autoimmune in nature, direct proof for this hypothesis is lacking. The purpose of this study was to determine in a murine model whether PVR can develop in the absence of T- or B-cell immunity.

Methods: Four- to six-week-old Rag-1 gene knockout (KO) and congenic wild-type mice (WT) on the C57.Bl/6 background were studied. PVR was induced by intravitreal injection of 3 μl dispase at the concentration of 0.2 U/μl. PVR development was monitored by electroretinograms, the macroscopic observation of hemorrhage, cataract, retinal folds, and of an uneven iris, as well as the histological detection of epiretinal membranes on haematoxylin-eosin stained tissue. Additionally, immunofluorescence analysis was performed. These manifestations of PVR were assessed 1, 2, 4, 6, and 8 weeks after the intravitreal injection.

Results: The data showed that the immune-deficient Rag-1 KO mice developed PVR with similar kinetics and severity as did the fully immune competent congenic WT mice. Carboxyfluorescein diacetate succinimidyl ester-labeled T cells that are specific for ovalbumin were detected in the inflamed vitreous and retina showing that T cells that are not specific for autoantigens present in the eye can migrate to PVR lesions. Therefore, the mere presence of T cells in PVR lesions does not imply an autoimmune pathogenesis.

Conclusion: This study suggests that T- and B-cell immunity is not essential for the induction of PVR.

Show MeSH
Related in: MedlinePlus