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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

Detection of OVA-specific T cells in PVR lesions at 48 and 72 h time point. OVA-specific, OT II TCR-transgenic T cells were labeled with CFSE and injected i.v. into congenic Rag-1 KO mice that received a simultaneous intraocular dispase injection. The mice were killed 12, 24, 48, 72, and 96 h later and cryosections of their eyes were studied for the presence of green-fluorescent (CFSE positive) cells. Hoechst 33342 dye was used to stain nuclei of the tissue blue. Anti-CD3 staining is show in red.
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fig4: Detection of OVA-specific T cells in PVR lesions at 48 and 72 h time point. OVA-specific, OT II TCR-transgenic T cells were labeled with CFSE and injected i.v. into congenic Rag-1 KO mice that received a simultaneous intraocular dispase injection. The mice were killed 12, 24, 48, 72, and 96 h later and cryosections of their eyes were studied for the presence of green-fluorescent (CFSE positive) cells. Hoechst 33342 dye was used to stain nuclei of the tissue blue. Anti-CD3 staining is show in red.

Mentions: We detected T cells in PVR lesions of WT mice at the chronic stage of the inflammatory process. Our observation, however, that PVR develops at a similar rate and severity in Rag-1 KO and WT mice suggests that these T cells in PVR regions might be bystander cells, that is, T cells with specificity for irrelevant antigens that are non-specifically recruited to the site of inflammation. To test this possibility, we studied whether T cells specific for OVA (an irrelevant antigen in the context of PVR) would migrate into PVR lesions. OVA-specific TCR transgenic T cells (that in addition were Rag-1−/− to assure that they express no additional endogenous TCR chains, and thus are specific for OVA only) were used to test this hypothesis. Such T cells were labeled with CFSE and injected into dispase-treated mice. CFSE-labeled cells were detected in the inflamed vitreous and retina at 48 and 72 h time point (Figure 4) showing that bystander T cells can migrate to PVR lesions. Thus, the presence of T cells in the PVR infiltrate does not imply that those T cells are specific for autoantigens expressed in the eye; their presence does not imply an autoimmune pathogenesis.


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)

Detection of OVA-specific T cells in PVR lesions at 48 and 72 h time point. OVA-specific, OT II TCR-transgenic T cells were labeled with CFSE and injected i.v. into congenic Rag-1 KO mice that received a simultaneous intraocular dispase injection. The mice were killed 12, 24, 48, 72, and 96 h later and cryosections of their eyes were studied for the presence of green-fluorescent (CFSE positive) cells. Hoechst 33342 dye was used to stain nuclei of the tissue blue. Anti-CD3 staining is show in red.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Detection of OVA-specific T cells in PVR lesions at 48 and 72 h time point. OVA-specific, OT II TCR-transgenic T cells were labeled with CFSE and injected i.v. into congenic Rag-1 KO mice that received a simultaneous intraocular dispase injection. The mice were killed 12, 24, 48, 72, and 96 h later and cryosections of their eyes were studied for the presence of green-fluorescent (CFSE positive) cells. Hoechst 33342 dye was used to stain nuclei of the tissue blue. Anti-CD3 staining is show in red.
Mentions: We detected T cells in PVR lesions of WT mice at the chronic stage of the inflammatory process. Our observation, however, that PVR develops at a similar rate and severity in Rag-1 KO and WT mice suggests that these T cells in PVR regions might be bystander cells, that is, T cells with specificity for irrelevant antigens that are non-specifically recruited to the site of inflammation. To test this possibility, we studied whether T cells specific for OVA (an irrelevant antigen in the context of PVR) would migrate into PVR lesions. OVA-specific TCR transgenic T cells (that in addition were Rag-1−/− to assure that they express no additional endogenous TCR chains, and thus are specific for OVA only) were used to test this hypothesis. Such T cells were labeled with CFSE and injected into dispase-treated mice. CFSE-labeled cells were detected in the inflamed vitreous and retina at 48 and 72 h time point (Figure 4) showing that bystander T cells can migrate to PVR lesions. Thus, the presence of T cells in the PVR infiltrate does not imply that those T cells are specific for autoantigens expressed in the eye; their presence does not imply an autoimmune pathogenesis.

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