Photo Credit: Marvin Samuel Tolentino Pineda
In this study, statins, such as simvastatin and lovastatin, demonstrated neuroprotective effects by mitigating gliosis in Müller cells and preventing retinal ganglion cell apoptosis induced by TNF-α release triggered by TRPV4 activation, suggesting their potential as a therapeutic avenue for glaucoma.
The following is a summary of “Modulation of TRPV4-mediated TNF-α expression in Müller glia and subsequent RGC apoptosis by statins,” published in the January 2024 issue of Ophthalmology by Choi et al.
This investigation aimed to explore the neuroprotective impact of statins on the apoptosis of retinal ganglion cells (RGCs) induced by activated Müller glia beyond their known role in cholesterol regulation. Cultures of primary Müller cells and RGCs were established from C57BL6 mice retinas. Müller cells were stimulated using GSK101, a transient receptor potential vanilloid 4 (TRPV4) agonist, and the subsequent release of tumor necrosis factor-alpha (TNF-α) into the culture medium was quantified through an enzyme-linked immunosorbent assay. Pretreatment with simvastatin or lovastatin was administered to cells before exposure to GSK101. RGCs were subjected to conditioned media from activated Müller cell cultures, and their apoptosis was evaluated using flow cytometry.
TRPV4 activation via GSK101 prompted gliosis in Müller cells, and the resulting conditioned media displayed significant potential in inducing RGC apoptosis. Statins exhibited the capability to mitigate both gliosis in Müller cells and the consequent apoptosis of RGCs. There was an observed elevation of TNF-α release into the media from GSK101-treated Müller cells, and TNF-α within the conditioned media emerged as the pivotal factor leading to RGC apoptosis. The upsurge in TRPV4-mediated TNF-α expression was linked to the activation of the nuclear factor kappa-light chain enhancer of the activated B cell pathway, a process impeded by statins. This study provides compelling evidence that statins can regulate gliosis and TNF-α expression in Müller cells, thereby safeguarding RGCs. These findings reinforce the neuroprotective potential of statins, positioning them as a prospective therapeutic avenue for treating glaucoma.
Source: sciencedirect.com/science/article/abs/pii/S0014483524000022