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Mechanism of steroid action
Steroids are the mainstay of many therapies in ophthalmology and much is known concerning their mode of action particularly at the transcriptional level where they appear to regulate the factor Nfat. However, steroids have multiple effects, many of which are undesirable in terms of their therapeutic anti-inflammatory role, and further knowledge of their specific anti-inflammatory role might lead to the development of newer more selective drugs. A recent paper (Nature Medicine1999;12:1424–7) has shown that glucocorticoids upregulate the expression of a hitherto unknown anti-inflammatory mediator and promote its release from monocytes and macrophages. This factor induces dispersion of leucocytes and lowers their adhesion to endothelial cells. It also inhibits their chemotactic response to fMLP and induces distinctive morphological changes. The activity correlates with a peptide known as thymosin beta4 sulphoxide which is specifically generated by monocytes in the presence of glucocorticoids and acts as a signal to inhibit an inflammatory response. In vivo, the oxidised form of the peptide potently inhibited inflammation in the mouse induced by carrageenin paw. The action of thymosin beta4 appears to be unique, because oxidation greatly enhances its extracellular signalling properties but appears to downregulate its effects on intracellular G-actin. In fact the authors suggest that this unique mechanism in which a cytosolic protein is converted to an extracellular mediator by methionine oxidation might have implications for drug discovery programmes and the development of new anti-inflammatory strategies.
tPA and intraocular use
tPA (tissue plasminogen activator) is currently used for a variety of intraocular disorders mostly related to fibrin deposition such as in vitreoretinal surgery for subretinal haemorrhage and for the resolution of …