Abstract
Purpose :
Elevated intraocular pressure (IOP) is the primary risk factor for glaucoma, and lowering IOP is the only known treatment. However, IOP fluctuates in a circadian manner, and there is some evidence that fluctuation in IOP may be a risk factor for disease progression. The purpose of this project was to better understand how the brain, and specifically the dorsomedial hypothalamus (DMH), regulates IOP. Previous work has shown that direct stimulation of the DMH induces IOP elevation. We hypothesized that stimulation of the SCN, the master time-clock for circadian rhythms, would increase intraocular pressure (IOP) and produce downstream excitation of neurons in the dorsomedial hypothalamus (DMH). c-Fos is a marker for neuronal activation, thus we investigated whether SCN stimulation would evoke IOP increases and c-Fos expression in the DMH
Methods :
Using a stereotaxic approach, a variety of substances were used to chemically stimulate the SCN of male Sprague-Dawley rats (250-320g). 1 h following stimulation, animals were euthanized and brains collected. 30µm coronal sections from the DMH region were collected and stained for c-Fos using fluorescently labeled antibodies. Two independent reviewers scored the regional staining intensities from 1-5.
Results :
c-Fos signaling in the DMH was not correlated to IOP response after SCN excitation. However, cFos signals within the paraventricular nucleus of the thalamus (PVT) were positively correlated with IOP increases after SCN excitation (R2=0.5, p<0.003). Neither heart rate, mean arterial pressure, nor intracranial pressure were significantly correlated with PVT c-Fos intensity or c-Fos levels in the DMH
Conclusions :
c-Fos immunoreactivity in the PVT that correlates with IOP increases following SCN stimulation may represent the first evidence of a role for the PVT in regulating IOP.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.