Intravenously Administered Anti-recoverin Antibody Alone Does Not Pass through the Blood-Retinal Barrier.
10.3341/kjo.2011.25.3.189
- Author:
Jeong Hun KIM
1
;
Jin Hyoung KIM
;
Dong Hun KIM
;
Woong Yang PARK
;
Kyu Won KIM
;
Young Suk YU
Author Information
1. Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Department of Ophthalmology, Seoul National University College of Medicine & Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea. ysyu@s
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Anti-recoverin antibody;
Blood-retinal barrier;
Cancer-associated retinopathy;
Intravenous administration;
Retina
- MeSH:
Animals;
Antibodies/*administration & dosage/*metabolism;
Blood-Retinal Barrier/*metabolism;
Cell Death/drug effects;
Cells, Cultured;
Female;
Injections, Intravenous;
Mice;
Mice, Inbred C57BL;
Recoverin/*immunology;
Retina/cytology/drug effects;
Retinal Vessels/metabolism
- From:Korean Journal of Ophthalmology
2011;25(3):189-195
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Cancer-associated retinopathy is a paraneoplastic retinal degeneration which may primarily result from auto-immune mediated apoptosis. It has been hypothesized that high titer of auto-antibodies are able to cross the blood-retinal barrier (BRB) and to enter retinal cells to activate apoptotic pathway which has been already well-established. However, it still remains to be elucidated whether auto-antibodies could cross BRB in the retina. Herein, we demonstrated that intravenously administrated anti-recoverin antibodies could not pass through BRB and not lead to retinal cell death. METHODS: Anti-recoverin antibody was intravenously injected to C57BL/6 mice, which were sacrificed 1 and 7 days to obtain eye. Vascular endothelial growth factor was intravitreally injected to induce BRB breakdown, which was confirmed by fluorescein angiography and western blotting for zonula occludens (ZO)-1, ZO-2 and occludin. To investigate the location of anti-recoverin antibody in the retina, immunofluorescein was performed. The retinal toxicity of intravenous anti-recoverin antibody was evaluated by histological examination and transferase-mediated dUTP nick-end labeling. Immunofluorescein staining for glial fibrillary acidic protein was done to address glial activation as well. RESULTS: Intravenously administrated anti-recoverin antibodies were exclusively distributed on retinal vessels which were co-localized with CD31, and led to neither increase of glial fibrillary acidic protein expression, as an indicator of retinal stress, nor apoptotic retinal cell death. Moreover, even in the condition of vascular endothelial growth factor-induced BRB breakdown, anti-recoverin antibodies could not migrate across BRB and still remained on retinal vessels without retinal cytotoxicity. CONCLUSIONS: Our results suggest that high titer of intravascular anti-recoverin antibodies could not penetrate into the retina by themselves, and BRB breakdown mediated by dysregulation of tight junction might not be sufficient to allow anti-recoverin antibodies to pass through BRB.
