June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
A Potential Role for the Hypothalamic Orexin System in Mediating Intraocular Pressure Fluctuations
Author Affiliations & Notes
  • Brian Samuels
    Department of Ophthalmology, Eugene & Marilyn Glick Eye Inst, Ind Univ, Indianapolis, IN
  • Nathan Hammes
    Department of Ophthalmology, Eugene & Marilyn Glick Eye Inst, Ind Univ, Indianapolis, IN
  • Philip Johnson
    Department of Anatomy, Indiana University, Indianapolis, IN
  • Anantha Shekhar
    Department of Psychiatry, Indiana University, Indianapolis, IN
    Clinical and Translational Sciences Institute, Indiana University, Indianapolis, IN
  • Footnotes
    Commercial Relationships Brian Samuels, Merck & Co., Inc (F), Merck & Co., Inc (C), ICHE (C); Nathan Hammes, None; Philip Johnson, None; Anantha Shekhar, Indiana University (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4013. doi:
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      Brian Samuels, Nathan Hammes, Philip Johnson, Anantha Shekhar; A Potential Role for the Hypothalamic Orexin System in Mediating Intraocular Pressure Fluctuations. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4013.

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

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Purpose: We have recently shown that chemical stimulation of the dorsomedial/perifornical hypothalamus (DMH/PeF) evokes increases in intraocular pressure (IOP), intracranial pressure (ICP), and the translaminar pressure gradient. The DMH/PeF region receives strong direct and indirect projections from the suprachiasmatic nucleus and has extensive efferent projections to autonomic sympathetic relays. Therefore, the DMH/PeF neurons are ideally situated to modulate circadian fluctuations in IOP. Orexins are a novel class of neuropeptides that play a key role in regulating circadian behaviors as well as neuroendocrine and autonomic functions. Given that orexin containing neurons are located almost exclusively in the DMH/PeF region, we hypothesize that fluctuations in IOP and ICP are regulated, at least in part, by these orexin containing neurons. To test this hypothesis, we examined the effect of a systemically administered orexin 1 receptor antagonist, SB334861 (Tocris), on the increases in IOP and ICP following chemical stimulation of the DMH/PeF with the GABA-A receptor antagonist bicuculline methoidide (BMI).

Methods: The cisterna magna space of isoflurane-anesthetized Sprague-Dawley rats (250-300g; n=18) was cannulated for continuous monitoring of ICP. The ICP line was then connected to high sensitivity pressure transducer attached to a PowerLab data acquisition system (AD Instruments). An iCareLab tonometer was used to record IOP every 2 minutes throughout the experiment. Rats received an injection of SB334861 (30mg/kg, i.p.) or vehicle 30 minutes prior to stereotaxic microinjection of BMI (30pmol/75nL) into the DMH/PeF region. The resulting increases in IOP and ICP were then recorded and differences between treatment groups determined by t-test with significance set at P≤0.05.

Results: Compared to vehicle control, pretreatment with the SB33486 attenuated the maximum increase in IOP (13.1±1.9 vs 7.7±1.0 mmHg; p=0.03) but not ICP (5.0±0.5 vs 3.9±0.7 mmHg; p=0.19) following chemical stimulation.

Conclusions: These data are the first to support the hypothesis that orexin neurons located in the DMH/PeF region play a role in mediating circadian fluctuations in IOP, a previously unrecognized function of these specific neurons. Further, these neurons may provide a novel target for future glaucoma therapies aimed at reducing circadian fluctuation of IOP.

Keywords: 568 intraocular pressure • 616 neurotransmitters/neurotransmitter systems • 458 circadian rhythms  

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