{Reference Type}: Journal Article
{Title}: Biomechanic, proteomic and miRNA transcriptional changes in the trabecular meshwork of primates injected with intravitreal triamcinolone.
{Author}: Park S;Raghunathan VK;Ramarapu R;Moshiri A;Yiu G;Casanova MI;Cosert K;McCorkell M;Leonard BC;Thomasy SM;
{Journal}: Vision Res
{Volume}: 222
{Issue}: 0
{Year}: 2024 Sep 10
{Factor}: 1.984
{DOI}: 10.1016/j.visres.2024.108456
{Abstract}: 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.