We aimed to provide a detailed analysis of substance P (SP)-containing nerves in the trabecular meshwork by ultrastructural immunohistochemistry and capsaicin treatment for chemical ablation of the sensory nerves. Numerous myelinated and unmyelinated nerves were observed inside the sheets and intertrabecular spaces of the trabecular meshwork, and the inner side of Schlemm’s canal. SP-like immunoreactive products were identified in some of these nerves and associated with numerous vesicles of different sizes, a few mitochondria and numerous neurotubili. After the capsaicin treatment, SP-like immunoreactive nerves persisted and no degenerated SP-like immunoreactive nerves were noted. On the basis of the ultrastructural features and the results of capsaicin treatment, it seems that these nerves are most probably autonomic in origin. Autonomic efferent SP-containing nerves are confirmed directly located in the trabecular meshwork; these have not been previously described at electron microscopic level. SP in autonomic efferent nerves might act as a neurotransmitter or neuromodulator for intraocular pressure regulation.

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