Articles
Physiology of Perfusion as It Relates to the Optic Nerve Head

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Abstract

Blood flow in the optic nerve has been demonstrated to be autoregulated, and, thus, within certain limits, to be independent of the local perfusion pressure. As in the brain, a close coupling of neuronal activity and optic nerve head blood flow has been demonstrated. A number of regulatory systems and factors participate in the regulation of vascular tone in various organs, including the optic nerve. Metabolic and myogenic mechanisms keep local perfusion constant or adapted to the local metabolic needs. Such mechanisms seem to be involved in the regulation of optic nerve blood flow as well. In contrast, neuronal blood flow regulation is of minor importance in the optic nerve. Many of the regulatory modalities induce a response of vascular smooth muscle cells through stimulation of factors produced by the endothelial cell layer. Indeed, endothelial factors are of utmost importance in the regulation of optic nerve blood flow. The facts that there is a basal formation of nitric oxide, which leads to an active dilation of the ocular vasculature, and that endothelin-1 decreases blood flow to the anterior optic nerve in a dose-dependent manner suggest that alterations in these regulatory mechanisms might be relevant for optic nerve blood flow alterations as they relate to glaucomatous optic neuropathy. It is hoped that a detailed knowledge of blood flow regulation in the optic nerve might initiate new treatment modalities in optic neuropathies that are hemodynamic and vascular in nature.

Section snippets

General Physiology of Blood Flow Regulation

Vascular resistance is physiologically regulated by changing the local diameter of the arterioles. A number of regulatory systems and factors, such as circulating hormones, as well as metabolic, myogenic, and neurogenic factors, participate in the regulation of the vascular tone (Fig. 1). Many of these regulatory modalities induce a response of the vascular smooth muscle cells through stimulation of factors produced by the endothelial cell layer.80 The following description will not separate

Blood Flow Autoregulation in the Optic Nerve

As an extension of the central nervous system (CNS), the optic nerve has several characteristics in common with other parts of the brain, including the autoregulation of blood flow.103, 107, 135, 136 In general, autoregulation keeps local perfusion constant or adapted to the local metabolic needs; thus, within certain limits, local perfusion remains largely independent of the local perfusion pressure. In various vascular systems, this is accomplished by two principal mechanisms: metabolic and

Humoral Control of Blood Flow

The circulating blood contains many vasoactive hormones acting on the general circulation partially through mediation of the endothelial cells and partially directly on the smooth muscle cells and pericytes of the vessels.71

Endothelial Vasoactive Factors

In the general circulation, the endothelial cells release vasoactive substances both spontaneously and after local stimulation (Fig. 2). Such stimulation can be chemical, e.g., circulating hormones, or physical, e.g., shear stress or wall tension. The locally released mediators can be classified into vasodilators (endothelial-derived relaxing factors [EDRFs]) and vasoconstrictors (endothelial-derived constricting factors [EDCFs]). The major EDRF is nitric oxide, which exerts a vasodilating

Range of Blood Flow Autoregulation

In addition to the intimate mechanisms pertaining to blood flow autoregulation, attention has been given to factors influencing the range of perfusion pressure within which the autoregulatory mechanisms are effective. In spontaneously hypertensive rats, the myogenic vascular response is shifted to higher perfusion pressures in the kidney,58 whereas experiments in rats demonstrated that arterial occlusive disease or drug-induced liver failure might lead to an impaired chemical vascular control

Vascular Regulatory Mechanisms in the Veins

The physiologic significance of the venous system has been somewhat neglected in vascular research on ocular blood flow regulation.31 In the ocular circulation, veins have mainly been considered passive conduits. In fact, the venules determine the output resistance of the microcirculatory bed and are very important in the control of the hydrostatic pressure of the blood in the exchange vessels and the filtration-resorption process. Direct microvascular pressure recordings in the cat

Endothelial Dysfunction in Glaucomatous Optic Neuropathy

Current evidence suggests that blood flow regulatory mechanisms might be altered in glaucoma. Endothelial dysfunctions have been observed in various vascular conditions, including hyperlipidemia, arteriosclerosis, hypertension, and vasospastic disorders.5, 21, 36, 75, 77, 78, 113 In glaucoma, plasma concentration of ET-1 tends to be higher in normal-tension glaucoma patients than in high-tension glaucoma patients or normal subjects.118 Furthermore, the physiologic increase in ET-1 plasma level

Method of Literature Search

Search terms included various combinations of the terms listed in the “key words” section of this review. A MEDLINE search was performed from 1990 to present. Articles obtained from the reference list of other articles were reviewed and included when considered appropriate. The main criterion for inclusion of the article was the present original importance to a particular subject.26

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      Citation Excerpt :

      Two important vasoactive substances released by the ECs after local stimulation by, for example, shear stress from pulsatile flow or uniaxial stretch, are nitric oxide (NO) and endothelin-1 (ET-1). A constant balance between the opposing functions of NO and ET-1 is necessary for proper regulation of the vascular system.156,157,232 NO is a potent vasodilator secreted by smooth muscle cells that causes the dilation of arterioles via activation of smooth muscle cells and the dilation of capillaries via pericytes.93

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    The authors did not indicate any proprietary or commercial interest in any product or concept discussed in this article.

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