May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Involvement of ATP Release in the Homeostatic Response of TM Cells to Mechanical Stress
Author Affiliations & Notes
  • J. Chow
    Ophthalmology, Duke University Eye Center, Durham, NC
  • P.B. Liton
    Ophthalmology, Duke University Eye Center, Durham, NC
  • C. Luna
    Ophthalmology, Duke University Eye Center, Durham, NC
  • P. Gonzalez
    Ophthalmology, Duke University Eye Center, Durham, NC
  • D.L. Epstein
    Ophthalmology, Duke University Eye Center, Durham, NC
  • Footnotes
    Commercial Relationships  J. Chow, None; P.B. Liton, None; C. Luna, None; P. Gonzalez, None; D.L. Epstein, None.
  • Footnotes
    Support  NEI EY016228 HIGHWIRE EXLINK_ID="47:5:1866:1" VALUE="EY016228" TYPEGUESS="GEN" /HIGHWIRE , NEI EY01894, NEI EY05722, RPB, HHMI
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1866. doi:
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    • Get Citation

      J. Chow, P.B. Liton, C. Luna, P. Gonzalez, D.L. Epstein; Involvement of ATP Release in the Homeostatic Response of TM Cells to Mechanical Stress . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1866.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To evaluate the potential role of ATP release from trabecular meshwork (TM) cells as a homeostatic mechanical stress–sensing mechanism capable of mediating cellular responses aimed at reducing aqueous humor outflow resistance in response to intraocular pressure (IOP) elevation.

Methods: : Experiments were conducted using primary cultures of porcine TM cells. Cyclic mechanical stretch (10% stretching/second) was generated using the Flexcell system. ATP release and ectoATPase activity induced by mechanical stress were measured using a luciferin/luciferase assay. Purinergic receptor–mediated ATP signaling was inhibited by suramin (0.1 mM). The effect of suramin on the IL–6 induction normally mediated by mechanical stress was analyzed by real time Q–PCR and ELISA.

Results: : Mechanical stress induced an increase in ATP release from TM cells (258%+/–23 at 15 min, 188%+/–11 at 30 min, and 900%+/–203 at 1 hour; p<0.017, n=4), as well as an increase in ectoATPase activity present in the extracellular media during the first 15 minutes of stress (57%+/–15%, p=0.011, n=4). No significant changes in ectoATPase activity were detected at 30 minutes or 1 hour after initiation of mechanical stress. Blockade of purinergic receptors with suramin resulted in inhibition of the mechanical stress–dependent induction of IL–6 mRNA and secretion of the IL–6 protein.

Conclusions: : Given the observed involvement of purinergic receptors in the mechanical stress–mediated upregulation of IL–6, the reported effect of IL–6 in increasing outflow facility, and the known role of purinergic receptors in cell volume regulation, the observed release of ATP and ectoATPases induced by mechanical stress in TM cells could contribute to activating cellular mechanisms aimed at increasing outflow facility. We hypothesize that elevated IOP causes mechanical stress to certain populations of TM cells that respond with ATP release and upregulation of IL–6 that might act distally in the outflow pathway to increase outflow facility.

Keywords: stress response • outflow: trabecular meshwork 
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