The multifunctional choroid

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Abstract

The choroid of the eye is primarily a vascular structure supplying the outer retina. It has several unusual features: It contains large membrane-lined lacunae, which, at least in birds, function as part of the lymphatic drainage of the eye and which can change their volume dramatically, thereby changing the thickness of the choroid as much as four-fold over a few days (much less in primates). It contains non-vascular smooth muscle cells, especially behind the fovea, the contraction of which may thin the choroid, thereby opposing the thickening caused by expansion of the lacunae. It has intrinsic choroidal neurons, also mostly behind the central retina, which may control these muscles and may modulate choroidal blood flow as well. These neurons receive sympathetic, parasympathetic and nitrergic innervation.

The choroid has several functions: Its vasculature is the major supply for the outer retina; impairment of the flow of oxygen from choroid to retina may cause Age-Related Macular Degeneration. The choroidal blood flow, which is as great as in any other organ, may also cool and warm the retina. In addition to its vascular functions, the choroid contains secretory cells, probably involved in modulation of vascularization and in growth of the sclera. Finally, the dramatic changes in choroidal thickness move the retina forward and back, bringing the photoreceptors into the plane of focus, a function demonstrated by the thinning of the choroid that occurs when the focal plane is moved back by the wearing of negative lenses, and, conversely, by the thickening that occurs when positive lenses are worn.

In addition to focusing the eye, more slowly than accommodation and more quickly than emmetropization, we argue that the choroidal thickness changes also are correlated with changes in the growth of the sclera, and hence of the eye. Because transient increases in choroidal thickness are followed by a prolonged decrease in synthesis of extracellular matrix molecules and a slowing of ocular elongation, and attempts to decouple the choroidal and scleral changes have largely failed, it seems that the thickening of the choroid may be mechanistically linked to the scleral synthesis of macromolecules, and thus may play an important role in the homeostatic control of eye growth, and, consequently, in the etiology of myopia and hyperopia.

Introduction

The choroid does not appear to be a mysterious tissue. It consists mostly of blood vessels, it supplies the outer retina, and choroidal defects cause degenerative changes and neovascularization. However, it is becoming increasingly evident that the choroid has at least three other functions: thermoregulation, adjustment of the position of the retina by changes in choroidal thickness, and secretion of growth factors. The last of these is likely to play an important role in emmetropization–the adjustment of eye shape during growth to correct myopia or hyperopia. What remains mysterious, at present, are the mechanisms behind the changes in choroidal thickness, the nature of its secretory functions and the relationship between these two processes.

In this review, we will summarize the anatomy, histology, innervation and functions of the choroid, discuss the control of choroidal thickness by visual signals, show evidence for a secretory role for the choroid and speculate on the relationship between changes in choroidal thickness and ocular elongation, and therefore, emmetropization.

Section snippets

Structure and “classical” functions of the choroid

The choroid is the posterior part of the uvea, the middle tunic of the eye (Fig. 1). The uvea develops from the mesenchyme surrounding the two vesicles that bud off the embryonic forebrain at the end of the first month in humans, eventually becoming the eyes. At about that time, melanocyte precursors migrate into the uvea from the neural crest; these do not differentiate into pigmented melanocytes until 7–8 months of gestation. The mesenchyme that forms the choriocapillaris at about 2 months

Modulation of choroidal thickness

Long ago, it was suggested that the choroid might participate in refractive adjustment as a slow accommodative mechanism (Kajikawa, 1923, Walls, 1942). Over 50 years later, renewed interest in the choroid was sparked by the confirmation of this hypothesis by showing that, in chickens, the choroid can increase its thickness in response to myopic defocus (image focused in front of the retina) by as much as 1 mm (>17 D) pushing the retina towards the image plane and compensating for much of the

The choroid and emmetropization

As the eye develops from birth to maturity it undergoes adjustments of its optical components so that most eyes eventually become emmetropic (focused for objects at distance). It is generally accepted that this “emmetropization” is determined by a combination of environmental (i.e., visual) and genetic influences. When this process goes awry, the eyes develop refractive errors (hyperopia or myopia). In the United States approximately 25% of the population is myopic (Sperduto et al., 1983) while

The diurnal rhythm in choroidal thickness and ocular growth

As mentioned above, the thickness of the chicken choroid shows diurnal oscillations, thickening during the night and thinning during the day (Nickla et al., 1998, Papastergiou et al., 1998), in approximate anti-phase to the diurnal rhythm in axial elongation. Both rhythms free-run in darkness and so are driven by an endogenous circadian oscillator, rather than being a response to darkness and light (Nickla et al., 2001). Furthermore, isolated scleral tissue exhibits a circadian rhythm of

Significance to human refractive disorders

The reasons behind the high incidence of myopia, particularly among educated people, remain obscure. The finding that animals can be made myopic by presenting them with hyperopic defocus by spectacle lenses argues that refractive error is under homeostatic control. Because the eye can alter its growth even if the optic nerve is severed, it follows that the retina is able to detect the sign of the defocus and control the eye's growth. Because chemical signals from the retina must pass through

Future directions

In this review, we have tried to bring together the literature bearing on the unusual aspects of the anatomy and function of the choroid. The knowledge concerning most of these aspects remains incomplete and hypotheses about choroidal functions remain tentative. In these final paragraphs, we will point to some research directions that might prove useful.

The most puzzling component of the choroid is the lamina fusca, about which nearly nothing is known. It would be interesting to assess what it

Acknowledgements

Supported by: NIH-EY-013636 (DLN) and EY-02727 and RR03060 (JW).

The authors are grateful to the following people for their important contributions: Jeffrey Kiel for his insightful discussions on the choroid and thermoregulation, and Falk Schrödl, Maria Egle De Stefano and Gerald Lutty for their excellent critical readings of the manuscript.

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