Level of glucocorticoid receptor mRNA expression in iris tissue and postoperative ocular inflammation in patients with uveitis.

Abstract

Glucocorticoids (GC) are widely used to treat uveitis, but their efficacy is known to vary substantially among patients. In this retrospective preliminary study, we measured the level of GC receptor (GCR) expression in ocular tissue taken from uveitis patients during cataract surgery as an indicator of their sensitivity to GC, divided the patients into comparatively high- and low-sensitivity groups on this basis, and compared the two groups with respect to the frequency of ocular inflammation attacks observed after operation. Iris samples were obtained from 13 patients during surgery for cataract associated with uveitis. From each sample, RNA was extracted and used as template for cDNA construction. The cDNA was exposed to GCR gene-detecting and TaqMan probes. The level of GCR mRNA expression was determined by real-time PCR and compared with the frequency of postoperative ocular inflammation attacks that occurred despite daily temporal and, as required, subconjunctival glucocorticoid injection or other therapy. The level of 18SrRNA expression was measured and taken as the mRNA expression baseline, and the ratio between the number of GCR and housekeeping gene18SrRNA copies was calculated as the normalized ratio. The mean normalized ratio was 13.7 for the uveitis patients and 7.3 for the uveitis-free control patients. The median normalized ratio in the uveitis patient group was 1.5. The mean frequency of inflammation attacks was 0.24/month in the uveitis patients with a normalized ratio of 1.5 or higher and 0.53/month in those with a normalized ratio of less than 1.5, a significant difference. The level of GCR expression may relate to the response to steroids in the clinical course of inflammation. Further investigation is warranted.