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The manuscript by Stamer et al. (1729) reports that eNOS knock-in transgenic mice have lower spontaneous IOP and higher pressure- dependent drainage of aqueous humor, presumably representing conventional (trabecular meshwork) outflow facility, than their wild-type counterparts. Further, the NOS inhibitor L-NAME normalized pressure-dependent drainage in the knock-in animals, while at IOP > 35 mmHg the pressure- flow relationship (i.e., the conventional outflow facility) in the wild-type mice increased and was indistinguishable from that continuously present in the eNOS knock-in mice at lower IOP. These beautifully conceived and impeccably executed experiments by a very strong multi-institutional/multi-national team establish several important concepts:
Thus the trabecular meshwork appears to be a self-coordinated functioning organ, aligned in some unknown way in a homeostatic drive toward a 'normal' IOP. The cytoskeleton/contractility mechanisms may be the efferent 'execution' arm of the reflexive/regulatory mechanism; their arrangement governs the final facility. The eNOS/NO system is a signal/transduction arm that mediates response to the stressors.
The existence of the TM as a responsive self-aware, self-regulating tissue/organ is supported. Concrete evidence of a NO based signal transduction mechanism as a crucial part of that system is provided
The actual 'sensors' to stress/strain/distension etc. within the trabecular meshwork are largely unknown, although some mechanosensory elements have been described in the anterior and posterior tendons of the ciliary muscle in primates, and in the muscle apex (the latter perhaps more related to the fine control of accommodation than to regulation of outflow facility).2-4
The Stamer article supports the existence of the TM as a responsive self-aware, self-regulating tissue/organ, and provides concrete evidence of a NO-based signal transduction mechanism as a crucial part of that system. Caveats about extrapolation from mice to primate/ human systems, and to a role in pathophysiology or treatment of POAG notwithstanding, this is a beautifully conceived, executed, interpreted and important piece of work.