Glaucoma, a leading cause of blindness globally, continues to present challenges in its treatment. The primary risk factor for glaucoma is elevated intraocular pressure (IOP), which causes the death of retinal ganglion cells (RGCs) and glaucomatous optic neuropathy. Current treatments primarily target reducing IOP but often fail to prevent the ongoing degeneration of RGCs and axons. Consequently, there is an urgent need for innovative therapies that can protect these vital cells. Recent research has focused on microRNAs (miRNAs) as potential regulators of glaucoma pathogenesis, offering new avenues for diagnosis and treatment.
MiRNAs play a crucial role in gene regulation after transcription and have been implicated in various physiological and pathological processes. In the study of glaucoma, miRNAs have gained significant attention, providing a promising field for understanding the disease’s development and identifying potential therapeutic targets. A previous study revealed that miR-93 promotes apoptosis in glaucomatous trabecular meshwork cells. By inhibiting miR-93, researchers observed increased cell viability, suggesting that it could be a potential target for glaucoma therapy.
To better understand miR-93’s role in glaucoma, researchers from Nanfang Hospital in China investigated its impact on retinal ganglion cells (RGCs) and its contribution to glaucoma development. They induced RGC apoptosis using oxygen-glucose deprivation and reperfusion (OGD/R) and found that miR-93 mimics significantly decreased RGC viability and promoted apoptosis. Conversely, miR-93 inhibitors increased cell viability and reduced apoptosis, indicating that miR-93 plays a role in promoting RGC apoptosis.
The study also examined miR-93’s effect in an acute glaucoma mouse model induced by high IOP. The results demonstrated that miR-93 mimics worsened retinal tissue damage, leading to a reduction in the number of cells in the ganglion cell layer and the thickness of various tissue layers. Intriguingly, miR-93 mimics significantly increased IOP levels, while miR-93 inhibitors reversed these changes, suggesting that miR-93 directly influences IOP in glaucoma.
Furthermore, the researchers explored miR-93’s impact on the extracellular matrix (ECM) and matrix metalloproteinases (MMPs), critical factors in glaucoma development. They discovered that miR-93 mimics upregulated ECM-related protein expression and downregulated MMPs in RGCs subjected to OGD/R induction. In the acute glaucoma mouse model, miR-93 mimics increased IOP levels and disrupted the balance between ECM and MMP-related proteins. However, inhibiting miR-93 restored this balance, decreasing IOP.
Additionally, the study revealed that miR-93 activates the Rho/ROCK signaling pathway, which has been implicated in glaucoma pathogenesis. Activation of this pathway was observed in both RGCs and retinal tissue when miR-93 was mimicked but inhibited when miR-93 was suppressed.
The findings of this study have significant implications for understanding glaucoma’s development and for the advancement of therapies and diagnostic markers. MiR-93 plays a significant role in promoting RGC apoptosis, exacerbating retinal tissue damage, influencing IOP levels, and disrupting the balance between ECM and MMP-related proteins. Moreover, it activates the Rho/ROCK signaling pathway, a key player in glaucoma pathogenesis.
While miR-93 shows promise as a potential therapeutic target for glaucoma, further research is necessary to identify its exact targets and potential adverse effects associated with manipulating its expression. Future investigations should focus on unraveling the intricate mechanisms through which miR-93 influences glaucoma, ultimately providing novel strategies for diagnosis and treatment. Overall, miR-93 represents a significant advance in our understanding of the molecular mechanisms underlying glaucoma pathogenesis, offering promising prospects for advanced therapies and diagnostic markers for this challenging eye disease. The study findings were published in the peer-reviewed journal Heliyon.