# Central Nervous System Control of Intraocular and Intracranial Pressure

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $372,267

## Abstract

Abstract
Glaucoma is a leading cause of blindness worldwide, yet the reason for retinal ganglion cell damage within the
optic nerve head (ONH) is not fully understood. Elevated intraocular pressure (IOP) is considered the primary
cause of glaucoma, but recent studies suggest that decreased intracranial pressure (ICP) also contributes to
glaucoma pathophysiology. IOP and ICP are dynamic, and evidence suggests that they are at least partially
under central nervous system (CNS) control. Understanding the neurophysiologic mechanisms that control IOP
and ICP variations is critical to understanding glaucoma pathogenesis and progression. Our lab has shown for
the first time that chemical stimulation of the dorsomedial hypothalamus and surrounding perifornical area
(DMH/PeF) in rodents evokes increases in IOP and ICP; however, there is a temporal shift in the time for each
of these measures to peak. This results in a change in the trans-ONH pressure difference (i.e. IOP minus ICP)
that is greater than the change in IOP or ICP alone. Further, defining this CNS pathway and the
neurotransmitters involved in IOP and ICP regulation may provide targets for novel glaucoma therapies aimed
at stabilizing the human translaminar pressure difference.
The primary focus of this grant is to examine the CNS pathways controlling IOP and ICP, the primary drivers of
the translaminar pressure difference in humans. Our central hypothesize is that central regulation of IOP and
ICP is controlled, at least in part, neurons located in the DMH/PeF region. To test this we have proposed 3
specific aims: 1) We will pharmacologically characterize the increases in IOP and ICP after site-directed
stereotaxic chemical stimulation of the DMH/PeF region using selective antagonists to various neurotransmitter
receptors. 2) We will attempt to define the central nervous system afferent inputs to and efferent targets of the
DMH/PeF neurons that might control IOP and ICP by using site-directed stereotaxic microinjections to
stimulate various central nervous system nuclei and record the changes in IOP and ICP. 3) We will examine
the role of certain specific neurotransmitters in regulating circadian changes in IOP and ICP by molecular-
based and pharmacologic-based inhibition of the neurotransmitter system while using radio-telemetry to record
IOP and ICP.

## Key facts

- **NIH application ID:** 9850969
- **Project number:** 5R01EY027316-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Brian Christopher Samuels
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $372,267
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850969

## Citation

> US National Institutes of Health, RePORTER application 9850969, Central Nervous System Control of Intraocular and Intracranial Pressure (5R01EY027316-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850969. Licensed CC0.

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