Transcriptomic analyses reveal the molecular mechanisms underlying the ocular surface damage in treated glaucoma patients

Abstract

Aims/Purpose: Topical glaucoma drugs have a high prevalence of ocular surface disease (OSD), affecting to its compliance. The clinical signs of OSD are very similar to those observed in patients with dry eye syndrome; however, the mechanisms mediating the onset of symptoms are unknown. The purpose of this study is to identify conjunctival transcriptomic changes in patients treated with topical medication and patients with dry eye and compare them to healthy controls.Methods: Impression cytology was performed, and samples were selected for RNA sequencing; 33 patients treated for glaucoma, 9 with dry eye and 14 healthy controls. After a quality check, the reads were aligned, and gene expression was quantified by counting exonic regions. Ingenuity Pathway Analysis identified the routes and biologic processes associated with transcriptomic changes.Results: In treated patients, up‐regulation of immune‐related genes represented the 79% of the altered pathways. In dry eye samples, immune system and inflammation represented 39% of the altered routes; increased expression of genes related to mitochondrial metabolism and oxidative stress represented 16% and decreased expression of genes involved in maintaining conjunctival integrity and cell differentiation represented 15%.Conclusions: According to our results, an exacerbation of the immune system is observed in patients with glaucoma treatment as the main pathway involved in ocular surface damage. However, in the case of patients with dry eye, the damage is the result of multiple pathways. Knowledge of the mechanisms involved in ocular surface damage is essential in the search for effective treatments for these patients.