4.7 Article

The ocular pulse decreases aqueous humor outflow resistance by stimulating nitric oxide production

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 320, Issue 4, Pages C652-C665

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00473.2020

Keywords

glaucoma; mouse models; ocular pulse; Schlemm's canal; trabecular meshwork

Funding

  1. NIH National Eye Institute [EY022359]
  2. BrightFocus Foundation [G2015145]
  3. Royal Academy of Engineering Fellowship
  4. Imperial College London President's Scholarship

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Intraocular pressure (IOP) fluctuates due to ocular pulse, which induces shear stress in Schlemm's canal (SC). The ocular pulse may modulate outflow facility by stimulating NO production. Studies showed the immediate increase in outflow facility in mice in response to the ocular pulse, with NO playing a significant role in this regulation.
Intraocular pressure (IOP) is not static, but rather oscillates by 2-3mmHg because of cardiac pulsations in ocular blood volume known as the ocular pulse. The ocular pulse induces pulsatile shear stress in Schlemm's canal (SC). We hypothesize that the ocular pulse modulates outflow facility by stimulating shear-induced nitric oxide (NO) production by SC cells. We confirmed that living mice exhibit an ocular pulse with a peak-to-peak (pk-pk) amplitude of 0.5mmHg under anesthesia. Using iPerfusion, we measured outflow facility (flow/pressure) during alternating periods of steady or pulsatile IOP in both eyes of 16 cadaveric C57BL/6J mice (13-14 weeks). Eyes were retained in situ, with an applied mean pressure of 8mmHg and 1.0mmHg pk-pk pressure amplitude at 10 Hz to mimic the murine heart rate. One eye of each cadaver was perfused with 100 mM L-NAME to inhibit NO synthase, whereas the contralateral eye was perfused with vehicle. During the pulsatile period in the vehicle-treated eye, outflow facility increased by 16 [12, 20] % (P < 0.001) relative to the facility measured during the preceding and subsequent steady periods. This effect was partly inhibited by L-NAME, where pressure pulsations increased outflow facility by 8% [4, 12] (P < 0.001). Thus, the ocular pulse causes an immediate increase in outflow facility in mice, with roughly one-half of the facility increase attributable to NO production. These studies reveal a dynamic component to outflow function that responds instantly to the ocular pulse and may be important for outflow regulation and IOP homeostasis.

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