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Brian C. Samuels, Nathan M. Hammes, Philip L. Johnson, Anantha Shekhar, Stuart J. McKinnon, R. R. Allingham; A Novel Hypothesis: The Dorsomedial Hypothalamus Regulates Circadian Fluctuations of Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1961.
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Fluctuation in intraocular pressure (IOP) has recently been identified as an independent risk factor for progression of glaucoma. We hypothesize that circadian fluctuations in IOP are regulated in part by neurons in the dorsomedial hypothalamus (DMH), a currently undescribed function of this nucleus. The purpose of this study was to determine whether site-directed chemical stimulation of the DMH evokes increases in IOP.
The femoral artery of isoflurane-anesthetized Sprague-Dawley rats (250-300g; n=6) were cannulated for continuous monitoring of heart rate (HR) and blood pressure (BP), while the cisterna magna space was cannulated to monitor intracranial pressure (ICP). The femoral artery and ICP lines were connected to high sensitivity pressure transducers attached to a PowerLab data acquisition system (AD Instruments). An iCareLab tonometer was used to record IOP every 2 minutes throughout the study. Using a stereotaxic approach, a microinjection of the GABA-A receptor antagonist bicuculline methoidide (BMI; 30pmol/75nL) was targeted to the DMH to stimulate the neurons. The resulting increases in HR, BP, ICP, and IOP were recorded.
These data are the first to support the notion that stimulation of neurons in the region of the DMH mediate increased IOP. The DMH receives strong direct and indirect projections from the suprachiasmatic nucleus (Chou et al., 2003) and has extensive efferent projections to autonomic sympathetic relays. Therefore, the DMH neurons are ideally situated to modulate circadian fluctuations in IOP. Broadening our understanding of this pathway may shed light on the mechanisms that underlie circadian fluctuations in IOP and may provide novel therapeutic targets for glaucoma therapy.
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