What Is the Link Between Vascular Dysregulation and Glaucoma?

doi:10.1016/j.survophthal.2007.08.010

Survey of Ophthalmology

Volume 52, Issue 6, Supplement, November 2007, Pages S144-S154

https://doi.org/10.1016/j.survophthal.2007.08.010 Get rights and content

Abstract

The need of blood flow to different organs varies rapidly over time which is why there is sophisticated local regulation of blood flow. The term dysregulation simply means that blood flow is not properly adapted to this need. Dysregulative mechanisms can lead to an over- or underperfusion. A steady overperfusion may be less critical for long-term damage. A constant underperfusion, however, can lead to some tissue atrophy or in extreme situations to infarction. Unstable perfusion (underperfusion followed by reperfusion) leads to oxidative stress. There are a number of causes that lead to local or systemic vascular dysregulation. Systemic dysregulation can be primary or secondary of nature. A secondary dysregulation is due to other autoimmune diseases such as rheumatoid arthritis, giant cell arteritis, systemic lupus erythematodes, multiple sclerosis, colitis ulcerosa, or Crohns disease. Patients with a secondary vascular dysregulation normally have a high level of circulating endothelin-1 (ET-1). This increased level of ET-1 leads to a reduction of blood flow both in the choroid and the optic nerve head but has little influence on autoregulation. In contrast, primary vascular dysregulation has little influence on baseline ocular blood flow but interferes with autoregulation. This, in turn, leads to unstable oxygen supply, which seems to be a relevant component in the pathogenesis of glaucomatous optic neuropathy.

Section snippets

Ocular Blood Flow (OBF)

In the following sections we will discuss the regulation of blood flow, in particular, the autoregulation as it is relevant to the pathogenesis of glaucomatous optic neuropathy (GON). In terms of mechanisms, we particularly emphasize the role of the endothelium cell layer, as there are indications that the major cause of primary vascular dysregulation is a vascular endotheliopathy.16, 68, 84, 94

Vascular Dysregulation

As mentioned previously, a regulation of circulation that is not properly adapted to the local needs is defined as vascular dysregulation. Such a dysregulation can be local (e.g., after rupture of an artherosclerotic plaque) or global. We will now focus on systemic dysregulation, which can be primary or secondary in nature.

Vascular Dysregulation and Ocular Blood Flow

This review focuses on systemic vascular dysregulation. “Systemic” implies the potential involvement of different organs, including the eye.54, 56 Although primary and secondary vascular dysregulation have many symptoms in common, their influence on eye circulation is distinctively different. As a result of increased level of vasoactive molecules such as ET-1, SVD leads to a more-or-less constant reduction of OBF, particularly in the choroid and ONH.¹⁰¹ SVD, however, does not essentially

Vascular Dysregulation and Glaucoma

It has been postulated for decades that ischemia might somehow be involved in the pathogenesis of GON.²⁹ For instance, blood flow velocity is, on average, slower in the retina, in the choroids,19, 46 and in the ONH47, 88, 107 in patients with glaucoma, in particular, normal-tension glaucoma. Blood flow is also reduced in retrobulbar vessels9, 35, 74, 95, 107, 118, 122 and in peripheral capillaries.22, 39, 61, 97 Classical risk factors for atherosclerosis like smoking, dyslipidemia, diabetes,

Method of Literature Search

A systematic search of the Medline database using the PubMed Web site for the years 1966 through June 2007 was conducted using the following key words: autoregulation, blood flow, blood flow regulation, blood pressure, Endothelin-1, endothelium, drug sensitivity, feeling of thirst, glaucoma, nitric oxide, sleep behaviour, vascular dysregulation, vasospasm. All articles read were in English and German, and when articles in other languages were of relevance, their abstracts in English were read.

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: The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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What Is the Link Between Vascular Dysregulation and Glaucoma?

Abstract

Section snippets

Ocular Blood Flow (OBF)

Vascular Dysregulation

Vascular Dysregulation and Ocular Blood Flow

Vascular Dysregulation and Glaucoma

Method of Literature Search

Baillieres Clin Rheumatol

J Am Coll Cardiol

Ophthalmology

Surv Ophthalmol

Ophthalmology

Surv Ophthalmol

Prog Retin Eye Res

Prog Retin Eye Res

Am J Ophthalmol

Am J Ophthalmol

Surv Ophthalmol

Am J Ophthalmol

Ophthalmology

Surv Ophthalmol

Prog Retin Eye Res

Surv Ophthalmol

J Clin Epidemiol

Can J Ophthalmol

Surv Ophthalmol

Jpn J Ophthalmol

Lancet

Am J Ophthalmol

Raynaud's phenomenon: subjective influence of female sex hormones

Int Angiol

Diurnal and nocturnal blood pressure drops in patients with focal ischemic glaucoma

Graefes Arch Clin Exp Ophthalmol

Fluorescein diffusion in the human optic disc

Invest Ophthalmol

Retinal vascular diameter in young subjects with a vasospastic propensity

Graefes Arch Clin Exp Ophthalmol

Systemic vascular endothelial cell dysfunction in normal pressure glaucoma

Br J Ophthalmol

Color Doppler imaging and plasma levels of endothelin-1 in low-tension glaucoma

Acta Ophthalmol Scand

Bilateral superior cervical ganglionectomy increases choroidal blood flow in the rabbit

Ophthalmologica

Enhanced endothelium derived hyperpolarising factor activity in resistance arteries from normal pressure glaucoma patients: implications for vascular function in the eye

Br J Ophthalmol

Is there a potential defect in the blood-retinal barrier at the choroidal level of the optic nerve canal?

Invest Ophthalmol

Ambulatory blood pressure monitoring in glaucoma patients. The nocturnal systolic dip and its relationship with disease progression

Int Ophthalmol

Regulatory mechanisms in the retinal and choroidal circulation

Ophthalmic Res

Vasospasm in glaucoma: clinical and laboratory aspects

Optom Vis Sci

Do patients with low tension glaucoma have particular cardiovascular characteristics?

Ophthalmologica

Choroidal haemodynamics in glaucoma

Br J Ophthalmol

The effects of distal limb warming on sleep latency

Int J Behav Med

Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120

J Immunol

Ocular blood flow alteration in glaucoma is related to systemic vascular dysregulation

Br J Ophthalmol

Acute myocardial infarction in a young woman with systemic lupus erythematosus

Vasc Med

Angiotensin, thirst, and sodium appetite

Physiol Rev

Permeability properties of the tissues in the optic nerve head region in the rabbit and the monkey. An ultrastructural study

Acta Ophthalmol (Copenh)

Psychophysical mechanisms and treatment of vasospastic disorders in normal-tension glaucoma

Bull Soc Belge Ophtalmol

[Glaucoma; A Guide for the Patient; An Introduction for Care-Providers; A Quick Reference]

Vascular dysregulation: a principal risk factor for glaucomatous damage?

J Glaucoma

Rapid autoregulation of cerebral blood flow: a laser-Doppler flowmetry study

J Cereb Blood Flow Metab

Circadian heart rate and blood pressure variability in autonomic failure

Rev Port Cardiol

The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine