%0 Journal Article
%T Biomechanic, proteomic and miRNA transcriptional changes in the trabecular meshwork of primates injected with intravitreal triamcinolone.
%A Park S
%A Raghunathan VK
%A Ramarapu R
%A Moshiri A
%A Yiu G
%A Casanova MI
%A Cosert K
%A McCorkell M
%A Leonard BC
%A Thomasy SM
%J Vision Res
%V 222
%N 0
%D 2024 Sep 10
%M 38991466
%F 1.984
%R 10.1016/j.visres.2024.108456
%X Although biomechanical changes of the trabecular meshwork (TM) are important to the pathogenesis of glucocorticoids-induced ocular hypertension (GC-OHT), there is a knowledge gap in the underlying molecular mechanisms of the development of it. In this study, we performed intravitreal triamcinolone injection (IVTA) in one eye of 3 rhesus macaques. Following IVTA, we assessed TM stiffness using atomic force microscopy and investigated changes in proteomic and miRNA expression profiles. One of 3 macaques developed GC-OHT with a difference in intraocular pressure of 4.2 mmHg and a stiffer TM with a mean increase in elastic moduli of 0.60 kPa versus the non-injected control eye. In the IVTA-treated eyes, proteins associated with extracellular matrix remodeling, cytoskeletal rearrangement, and mitochondrial oxidoreductation were significantly upregulated. The significantly upregulated miR-29b and downregulated miR-335-5p post-IVTA supported the role of oxidative stress and mitophagy in the GC-mediated biomechanical changes in TM, respectively. The significant upregulation of miR-15/16 cluster post-IVTA may indicate a resultant TM cell apoptosis contributing to the increase in outflow resistance. Despite the small sample size, these results expand our knowledge of GC-mediated responses in the TM and furthermore, may help explain steroid responsiveness in clinical settings.