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A. M. Nguyen, S. Saraswathy, N. A. Rao; Photoreceptor A Crystallin Upregulation Is Induced by TLR4 Mediated Innate Immune Response. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5452.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous studies indicate that A crystallins prevent photoreceptor mitochondrial oxidative stress mediated apoptosis in early EAU. This study investigated the role of TLR4 activation in the upregulation of A crystallin in the retinas of animals with early EAU.
B6.Cg-Foxn1nu(nude mice), TLR4-/- (C57BL/6) and wild type (WT) control (C57BL/6) animals were immunized with IRBP mixed with complete Freund’s adjuvant; eyes were enucleated on day 7 post immunization. RNA extracted from the retinas underwent real-time PCR to detect gene expression of TNF-, iNOS and A crystallin. Retinal cryosections from TLR4-/- and WT controls were also immunostained to localize expression of NFkB, TNF-, iNOS and A crystallin; oxidative DNA damage was studied through 8-hydroxy-deoxyguanosine (8-OHdG) staining.
The WT controls and nude mice revealed TNF-, iNOS and A crystallin upregulation in the retina; but such upregulation was absent in TLR4-/- mice retina. The immunostains revealed iNOS and A crystallin in the photoreceptor inner segments and inner nuclear layer in the WT controls; but such positive staining was absent in the TLR4-/- mice. NFkB and TNF- also showed intense staining in WT controls in the inner segments of the photoreceptors and the outer plexiform and inner nuclear layers, whereas in TLR4-/- mice such staining was absent. In the WT controls, intense OHdG staining was detected in the inner segment of the photoreceptor layer and in the inner nuclear and outer plexiform layers; such staining was markedly reduced in the inner segments and absent in the remainder of the retina in TLR4-/- mice.
The above results suggest that oxidative stress is induced and A crystallin expression is increased during early EAU. These molecular events could be mediated by innate immunity mainly through the TLR4 pathway.
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