Research Summary

Role of micro RNAs in the regulation of glucocorticoid receptor (GR) signaling and development of new therapeutics for steroid-induced glaucoma

Glucocorticoid –induced glaucoma is an important clinical condition associated with the use of steroids in patients with various inflammatory or autoimmune diseases. GC-induced glaucoma as a side-effect associated with steroid use is very common in steroid responders. The responsiveness of steroid varies among the patients and the susceptible individuals are at great risk of developing optic neuropathy leading to blindness. It is reported that, 40% of the general population showed increased intraocular pressure (IOP) due to dexamethasone (steroid) use and 6% of these patients will develop glaucoma.

Patients with primary open angle glaucoma (POAG) are 100% steroid responders which eventually enhance the susceptibility of losing vision.  However, the molecular basis for such responsiveness towards steroids is not very well understood. Through this fellowship, I hope to address why some respond to steroids and why some are more susceptible to develop secondary glaucoma and why not others? We hypothesize that the microRNAs (small non-coding RNA) have a regulatory role in mediating glucocorticoid receptor signaling and the development of miRNA mimics / inhibitors would be beneficial for GC-induced glaucoma. By proving this mechanism in ex vivo model system using human donor eyes, we would be able to predict the susceptible individuals with the specific set of microRNAs as a biomarker and to target for GC-induced glaucoma in the clinical set up.

Figure Legend: Picture showing the establishment of HOCAS ex vivo model using human donor eyes