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H. Kim, R. N. Fariss, M. Thill, C. Zhang, K. G. Csaky; The Study Of Retinal Penetration Of Intravitreal Full-length Immunoglobulin G In Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):99.
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The distribution and fate of intravitreally administered antibody is poorly understood. In this study, the penetration of intravitreal full-length IgG was determined in vivo in both normal and injured rat retina.
20 ug of Alexa 555 conjugated goat anti-rabbit IgG (H+L) was injected intravitreally into normal, post-mortem, or laser photocoagulated rat eyes. The eyes were enucleated, isolated retinas embedded in 7% agarose and sectioned into 100 um-thick slices. Mouse anti-glutamine synthetase or a mouse anti-FcRn IgG1 was used to localize the Muller cells or the FcRn receptor, respectively and localization was analyzed with confocal microscopy.
The intravitreal IgG overcame the inner limiting membrane barrier and then penetrated in parallel through the extracellular matrix into the deep retinal structures by passive diffusion, not specifically through the Muller cells as previously reported. The IgG diffusing in the retina could not pass across the external limiting membrane because of the physical limitation in a normal retina. On the other hand, the interface between the inner plexiform layer and the inner nuclear layer were formidable barrier against the retinal penetration of intravitreal IgG in a dead retina. In a laser photocoagulated retina, the intravitreal IgG diffused easily into the sub-retinal space and the Bruch's membrane due to the disruption of the retinal structures including the inner limiting membrane and the external limiting membrane. The intravitreal antibody was detected at both the inner luminal and the abluminal sides of the retinal blood vessels, which form tight junction complexes. The expression of FcRn receptor was determined in the inner retinal blood vessels by an immunohistochemistry study.
In a normal retina, the inner limiting membrane was a formidable barrier, but not an absolute one. The retinal blood vessels might play an important role in the penetration of the intravitreal antibody. The existence of the FcRn receptor indicates possibility of the penetration of the tight junction of the inner blood retinal barrier by the transcytosis via the receptor.
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