Diminished ocular tgf-β2 concentration and mrna levels during ocular inflammation correlate with severity of disease
Ocular inflammation is influenced by the local production of TGF-B2, which downregulates ocular immune and inflammatory responses via blockade of effector T cell activation and suppression of macrophage function. Previously, it has been demonstrated that ocular TGF-β2 declines during inflammation. We sought to determine if the decline in ocular TGF-β2 protein correlates with a decline in TGF-β2 mRNA levels and if the loss correlates with the severity of inflammation. Experimental inflammation was induced in immunized rabbits by intraocular injection of antigen. At day 1,3 and 7 following induction, clinical examination was performed and ocular fluids were aspirated for determination of TGF-β2 and cellular infiltration. The iris and ciliary body were removed for total RNA, and competitive RT-PCR was performed to quantify mRNA. Ocular levels of bioactive TGF-β (all isoforms) were significantly decreased during inflammation. Immunoreactive (total) TGF-β2 also decreased by day 3 from 3.4±0.2 ng/ml in normals to 0.38±0.14 ng/ml. This decline was associated with a 15-fold decrease in TGF-β2 mRNA by day 1 which persisted through day 7. A significant correlation between ocular TGF-β2 mRNA and immunoreactive TGF-β2 was observed when concentrations from the same eye were compared (r=0.49, p=0.042). Also, a significant inverse correlation was observed between TGF-β2 mRNA concentration and the severity of clinical inflammation (r=-0.68, p=0.003) or vitreous cell concentration (r=-0.76, p=0.0004). Loss of TGF-β2 from the eye correlates with a decline of TGF-62 mRNA in iris and ciliary body, suggesting that transcriptional down-regulation of TGF-B2 occurs during ocular inflammation.
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