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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Differentiating intraocular glucocorticoids.

BACKGROUND: Natural corticosteroids (e.g. hydrocortisone) and synthetic selective glucocorticoid (GC) agonists have been used by ophthalmologists for decades to treat various forms of ocular inflammation. More recently, increased clinical use of locally delivered GC has shown significant benefit for the treatment of multiple retinal indications including macular edema associated with uveitis, retinal vascular occlusions and diabetes. Our current understanding of the clinical utility of specific intraocular GC far surpasses our knowledge of their biologic and pharmacologic activities in the eye. OBJECTIVE: To present an update on GC receptor (GR) biology in general and as it applies to the eye, and discuss the pharmacokinetics, delivery and pharmacology of the commonly used intraocular GC dexamethasone (DEX), triamcinolone acetonide (TA) and fluocinolone acetonide (FA). RESULTS: DEX, TA and FA are structurally similar but significantly differentiated by their aqueous and lipid solubility, delivery system requirements, pharmacokinetics and interactions with functional GR. Culture of human trabecular meshwork cells and full transcriptome microarray analysis reveals that DEX, TA and FA generate unique gene transactivation and repression profiles as well as potentially distinct biologic responses that are not only steroid structure dependent, but also dose and time dependent. Finally, DEX and FA markedly protect photoreceptors from degenerating in animal models of excessive light and retinitis pigmentosa, respectively. CONCLUSION: It is tempting to speculate that the unique pharmacokinetic and pharmacologic profiles of the commonly used intraocular steroids and novel future drugs may reveal significant differences in their therapeutic value in patients with macular edema or other inflammatory disease, in their ocular adverse side effect profile, and their ability to normalize glial and neuronal function in diseased retina.[1]


  1. Differentiating intraocular glucocorticoids. Edelman, J.L. Ophthalmologica (2010) [Pubmed]
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