Retinal and optic nerve head ischemic disorders and atherosclerosis:: Role of serotonin

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Abstract

Ischemic disorders of the retina and optic nerve head (OPH) constitute a common cause of visual loss in the middle-aged and elderly population. These disorders have a high association with atherosclerosis. This review has considered the various aspects of atherosclerosis and its role, as well as that of serotonin, in the development of ischemic disorders of the retina and ONH. It is known that when platelets aggregate on an atheromatous plaque, serotonin is one of the agents released. Studies in experimental atherosclerotic monkeys have shown that, although serotonin has no effect on ocular vasculature in normal monkeys, in atherosclerotic monkeys it produces vasospasm of the central retinal artery (CRA) and/or posterior ciliary artery (PCA) in various combinations but not vasospasm of the arterioles in the retina; vasospasm of the CRA and/or PCA(s) can consequently cause transient, complete occlusion or impaired blood flow in these arteries. It is postulated that in some atherosclerotic individuals this mechanism may play an important role in the development of ischemic disorders of the retina and ONH, including amaurosis fugax, (CRA) occlusion and anterior ischemic optic neuropathy, and possibly also glaucomatous optic neuropathy, particularly in normal tension glaucoma. Studies have also shown that dietary treatment of atherosclerosis abolishes or markedly improves the serotonin induced vasoconstriction within a few months. All these considerations may have important implications for our understanding of the pathogenesis and management of these blinding disorders.

Introduction

Ischemic disorders of the retina and optic nerve head (ONH) constitute a common cause of visual loss. These disorders are usually seen in middle-aged and elderly people although they do occur in younger persons also. A common systemic abnormality seen in these patients is evidence of atherosclerosis and/or hyperlipidemia (Hayreh and Podhajsky, 1982; Hayreh et al., 1994b). It has generally been taken for granted that in atherosclerotics, ocular ischemic disorders are usually secondary to embolization or hemodynamic disturbances caused by the atherosclerotic lesions or marked stenosis/thrombosis respectively in the regional arteries.

Atherosclerosis is recognized as the chief cause of death in the United States and in Western Europe (Arteriosclerosis, 1971). In these countries, cardiovascular disease is responsible for substantial mortality and morbidity and atherosclerosis is the most common cause of it. Obesity and atherosclerosis are far more common in races with a high-fat diet and in higher income groups, so that atherosclerosis is clearly a curse of affluent societies. Arterial hypertension and diabetes mellitus are also prevalent in these societies. There is evidence that arterial hypertension aggravates atherosclerosis. A large body of clinical, epidemiological and experimental evidence has accumulated linking hypertension in the presence of a potentially atherogenic diet to an increased incidence and severity of atherosclerosis and its sequelae (McGill et al., 1961; Hollander, 1966, Hollander, 1973; Veterans Administration Cooperative Study Group on Antihypertensive Agents, 1967; Smirk, 1972; Dustan, 1974; Hollander et al., 1976, Hollander et al., 1977). It has been shown that in patients with non-insulin-dependent diabetes mellitus, fasting and postprandial concentrations of triglyceride-rich lipoproteins, especially very-low-density lipoproteins, are higher and those of high-density lipoprotein are lower than among non-diabetics (Kannel, 1985; Howard, 1987; Taskinen, 1990; Chen et al., 1993; Syvänne et al., 1994). When the catabolism of triglyceride-rich lipoproteins is impaired, they become cholesterol enriched and possibly directly atherogenic (Miesenböck and Patsch, 1992). Thus, a combination of high-fat diet, arterial hypertension and diabetes mellitus contribute to a high incidence of atherosclerosis in the United States and Western countries, and consequently to the prevalent diseases caused by atherosclerosis, and their associated high morbidity and mortality. In view of all these considerations, study of various aspects of atherosclerosis has become an important medical issue during the past several decades. Although marked advances have been made in the cardiovascular field on atherosclerosis, the study of the role of atherosclerosis in ocular vascular disorders and blindness has lagged seriously.

Section snippets

Atherosclerosis

It was Hodgson (1815), who published the first chemical analysis of atherosclerotic plaque, and Lobstein (1829)introduced the term “atherosclerosis”. Atherosclerosis has been found in autopsies of ancient Egyptian mummies, including that of Amenhotep II, King of Egypt from 1450 to 1425 BC (Ruffer, 1911).

Mechanisms of vasoconstrictor response to serotonin

Numerous studies have shown increased vasoconstriction in response to serotonin in atherosclerotic arteries (Henry and Yokoyama, 1980; Heistad et al., 1984, Heistad et al., 1987a, Heistad et al., 1987b; Vanhoutte and Houston, 1985; Faraci et al., 1989, Faraci et al., 1991b) and normalization with regression of atherosclerosis (Heistad et al., 1987b; Faraci et al., 1991a; Benzuly et al., 1994). The mechanisms responsible for these changes are not fully understood. Many processes may be

Blood supply of the posterior segment of the eye and optic nerve head

The CRA and the PCAs, both branches of the ophthalmic artery, supply the blood to the posterior segment (Hayreh, 1962). In 60% of eyes the CRA may arise from the ophthalmic artery by a common trunk with one or more of the PCAs (Singh and Dass, 1960a)—this fact has an important clinical application in understanding the development of combined and simultaneous retinal and ONH ischemic lesions.

  • 1.

    (a) Central retinal artery: this supplies the entire inner part of the retina (up to the inner nuclear

Ocular ischemic disorders

Occlusion of the CRA and/or PCAs can produce a variety of retinal and optic nerve ischemic disorders. The ischemic lesions may be transient or permanent. There is also overwhelming evidence now suggesting that the ONH damage and visual loss in glaucoma is due to vascular insufficiency to the ONH (Hayreh, 1994).

Future directions

Acute ischemic disorders of the retina and ONH constitute one of the major causes of marked visual loss in middle-aged and elderly people, who usually have a high incidence of systemic disorders such as hypercholesterolemia, atherosclerosis, arterial hypertension and diabetes mellitus. It is fairly well established that atherosclerotic changes in the regional arteries, associated with these systemic disorders, do play an important role in the development of ischemic disorders of the eye and

Acknowledgements

This study was supported by an unrestricted grant from the Research to Prevent Blindness Inc. New York.

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    Dr S. S. Hayreh is a Research to Prevent Blindness Senior Scientific Investigator.

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