Abstract
Purpose :
PIEZO1 and PIEZO2 are proteins expressed in mechanosensitive channels, and they detect mechanical forces in a number of different tissues. The potential source of mechanosensitivity in the extraocular muscles is unclear for both myofibers and myogenic precursor cell activation. We examined human, monkey, and mouse extraocular muscles for the expression of these mechanosensitive channels.
Methods :
We performed immunohistochemical staining for PIEZO1 and PIEZO2 expression in cross-sections of the extraocular muscles from humans, monkey, and mice. We co-stained for the presence of the following in selected sections: nuclei using Hoechst dye; myogenic precursor cells with an antibody against PITX2; neurofilaments to detect nerve fibers; and PAX7 using a reporter mouse where the PAX7-positive cells express tdTomato. These stained sections were examined using a Keyence or Leica microscope.
Results :
The extraocular muscles contained small mononucleated cells that were positive for PIEZO1 and PIEZO2. These were found to co-express PITX2 but not PAX7. All of the extraocular muscles examined also contained nerve fibers positive for the phosphorylated neurofilament protein that co-expressed PIEZO1 and PIEZO2. Most of the PIEZO1- and PIEZO2-positive nerve fibers had small diameters and were found in and around individual myofibers. The majority of large neurofilament-positive nerve fibers in bundles were PIEZO-negative.
Conclusions :
Previous studies in limb muscle demonstrated that PIEZO1 expression is important for the ability of muscle precursor cells to maintain a regenerative state. As there is continuous myonuclear turnover in the extraocular muscles, PIEZO1 and PIEZO2 may play a critical role in their ability to sense muscle stretch, respond quickly, and maintain the large population of activated myogenic precursor cells that are responsible for this process in the extraocular muscles. In addition, while currently the neuronal source of these nerve endings in the extraocular muscles is unclear, their presence in mice, monkey, and human nerve fibers suggests they are a conserved population. We hypothesize that these PIEZO1- AND PIEZO2-positive nerve fibers are critical for the transmission of stretch-related information to the ocular motor system in the brain.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.