Abstract
Purpose :
Neuron cell bodies within the brain and brainstem can be experimentally manipulated to alter intraocular pressure (IOP). The suprachiasmatic nucleus (SCN) of the anterior hypothalamus receives direct input from the retina and is known to regulate circadian rhythms, including IOP. However, our previous data suggested that neither GABAergic nor glutamatergic modulation of the SCN caused a change in IOP, yet microinjection of a hypertonic, hyperosmotic buffer into the SCN caused an IOP spike. Our goal is to understand regulatory pathways for IOP within the central nervous system. Here we tested the effect of injecting a hyperosmotic, but hypotonic, mannitol solution into the SCN on IOP.
Methods :
Male Sprague-Dawley rats (n=39) were anesthetized at midday. A 75 nL injectate of a hyperosmotic 20% mannitol solution in water (1,098 mOsmol), or a hyperosmotic and hypertonic PBS solution (578 mOsmol), or a chemical neurotransmitter agonist or antagonist, or a control artificial cerebrospinal fluid solution (311 mOsmol) were microinjected into the SCN while recording IOP by tonometer. cFos was localized in post-mortem brain sections by direct immunofluorescence.
Results :
A 20% mannitol solution did not significantly increase IOP above background. All IOP responses were negatively correlated with cFos immunopositive cells in the SCN (R2 = 0.54, p<0.0002), but positively correlated with cFos expression in the paraventricular nucleus of the thalamus (PVT, R2 = 0.79, p<0.0001).
Conclusions :
High levels of SCN cFos activity were associated with baseline levels of IOP. A hyperosmotic mannitol solution had no effect on either cFos signal or IOP, similar to lack of effect by GABAA receptor antagonists, or glutamatergic antagonists and agonists alone. An elevation of IOP was produced by a hypertonic phosphate buffer injection and associated with low post-mortem SCN cFos levels. PVT cFos levels, however, were directly correlated with IOP and may play a regulatory IOP role.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.