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Considering the mechanics of intraocular pressure, we are used to think of two independent, anatomically and biologically distinct processes, whose combined and balanced effects result in the build-up of the normal IOP: the production of aqueous humor by an active epithelial pump and the resistance to outflow in the two main drainage pathways.
But could it be that there is a single 'orchestra conductor' that supervises and controls both processes, ultimately regulating intraocular pressure? This conductor could be the ciliary body. On the one hand, it is in the non-pigmented epithelial (NPE) cells of the ciliary processes that carbonic anhydrase catalyzes hydration of CO2 into hydrogen and bicarbonate ions, effectively pumping water into the eye. On the other hand, the high levels of these same bicarbonate ions in the NPE cells could well be responsible for the regulation of anterior chamber drainage, as Lee et al. (1732) argued in this paper.
High ciliary bicarbonate levels linked to aqueous inflow, could facilitate outflow through a communicative pathway with the drainage tissue, effectively maintaining IOP homeostasis
What could be the biochemical pathway and messengers through which the ciliary body communicates with the drainage tissues? The authors hypothesize ‐ and provide substantial experimental evidence ‐ that soluble adenylyl cyclase (sAC) is abundantly present in the NPE cells and stroma of the ciliary body. Inhibition of sAC (by the specific inhibitor KH7) resulted in reduction of locally produced cAMP, decrease in trabecular outflow facility and increase in IOP in vivo. Conversely, sAC stimulation by addition of bicarbonate resulted in an increase of cAMP production in vitro. Given the fact that sAC is absent from the drainage pathways, the authors speculate that the trabecular drainage mechanism is regulated by the bicarbonate sensitive sAC located in the ciliary processes and that a communicative pathway exists between the ciliary body and the drainage tissues via specific messengers secreted in the aqueous humor, whose nature is yet to be determined. High bicarbonate levels linked to aqueous inflow would thus facilitate outflow through this communicative pathway, effectively maintaining IOP homeostasis. The identification of the messengers involved in this pathway could open new avenues for the development of novel glaucoma therapies.