Purchase this article with an account.
Mahita Kadmiel, Sivapriya Ramamoorthy, John Cidlowski; Glucocorticoid Receptor Role in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):887.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glucocorticoids are widely used in the treatment of ocular disorders. However, the physiological function of retinal glucocorticoid receptor (GR) is poorly understood. Glucocorticoid receptor signaling activates anti-inflammatory responses in various organs in the body. Therefore, we hypothesize that the glucocorticoid receptor in the retina functions to regulate the inflammatory response and thereby maintain retinal homeostasis.
Mice with conditional deletion of the glucocorticoid receptor in the retina (RetinaGRKO mice) were generated by intercrossing GRflox/flox mice (Oakley RH, 2013) and RxCre mice (Swindell E.C, 2006). At 2 months of age, control and knockout male mice were euthanized and their eyes were harvested for downstream analysis. Reduction in GR mRNA and protein level in the retinas from RetinaGRKO mice was determined by RT-PCR, western blotting and immunohistochemistry. For histological and immunofluorescence studies, paraformaldehyde-fixed eyes were cryoprotected in sucrose and embedded in OCT compound before cryosectioning. For gene expression studies, NanoString technology was used to measure the expression of 248 genes involved in inflammation.
Immunofluorescence in adult wild type mice revealed that glucocorticoid receptor is expressed predominantly by the Muller glial cells of the neural retina and by the retinal pigmented epithelium. Compared to the control animals, Retina GRKO mice exhibited a 60% reduction in glucocorticoid receptor, both at the mRNA level and the protein level. Loss of GR in the retina results in the thinning of the inner nuclear layer of the peripheral retina. Furthermore, NanoString analysis revealed that glucocorticoid receptor is important for retinal homeostasis, as the expression level of 26 inflammatory genes was significantly altered in RetinaGRKO mice (ANOVA p value <0.05). Members of the toll-like receptor family and of the complement system were among the genes whose expression was significantly altered in the absence of the glucocorticoid receptor.
Our results suggest that retinal glucocorticoid receptor plays a critical role in maintaining retinal homeostasis by regulating the inflammatory response. Future studies involving electroretinograms would reveal the functionality of retinas in the absence of glucocorticoid receptor. Findings from this study may lead to improved glucocorticoid-based therapies for inflammatory diseases of the retina.
This PDF is available to Subscribers Only