Abstract
Purpose :
Because of the lack of a specific molecular marker, the question has not been answered conclusively if there are specific proprioceptive sensory nerve endings in the human chamber angle that serve as mechanoreceptors. Piezo2 has been identified as a mechanosensitive ion channel that plays a role in rapidly adapting mechanically activated currents in somatosensory neurons. To clearly identify proprioceptive nerve endings in the human chamber angle, we investigated anterior segments of human eyes for the presence of Piezo2-containing nerve endings.
Methods :
Human autopsy eyes (age >80 years) without any obvious ocular pathology were investigated. The anterior eye segment was dissected in quadrants. From each quadrant, wedge-shaped specimens with 1.6 mm width on average, and containing trabecular meshwork and ciliary muscle were cut. The specimens were fixed in 2 % paraformaldehyde for immunohistochemistry or Karnovsky’s solution for transmission electron microscopy (TEM). Serial tangential 12-20 µm cryosections were cut and immunostained with antibodies against Piezo2. To distinguish axons from terminal nerve endings, double immunohistochemistry was performed combining Piezo2 antibodies with antibodies against synaptophysin that specifically stains synaptic vesicles in nerve terminals.
Results :
Piezo2 immunoreactive axons were identified in iris and ciliary muscle. Piezo2/synaptophysin immunoreactivity was detected almost exclusively in club- or bulb-shaped nerve terminals in the scleral spur (75 %) or, more inwardly, at the apex of the longitudinal portion of the ciliary muscle. The nerve endings were considerably larger (17.7 µm on average) than sympathetic or parasympathetic terminals and resembled Ruffini-like sensory nerve endings as present e.g., in the carotid sinus. TEM confirmed that the nerve endings were identical with putative mechanosensory nerve endings previously identified based on ultrastructural criteria (Tamm et al., IOVS 1994).
Conclusions :
We conclusively confirm the presence of mechanosensory nerve terminals that measure stress or strain of the scleral spur extracellular matrix. Such changes are likely induced by ciliary muscle contraction and/or changes in intraocular pressure.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.