Josh Wallman

THE MULTIFUNCTIONAL CHOROID

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.

Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks

It is known that when hyperopic or myopic defocus is imposed on chick eyes by spectacle lenses, they rapidly compensate, becoming myopic or hyperopic respectively, by altering the depth of their vitreous chamber. Changes in two components--ocular length and choroidal thickness--underlie this rapid compensation. With monocular lens treatment, hyperopic defocus imposed by negative lenses resulted in substantially increased ocular elongation and a slight thinning of the choroid, both changes resulting in myopia; myopic defocus imposed by positive lenses resulted a dramatic increase in choroidal thickness, which pushed the retina forward toward the image plane, and a slight decrease in ocular elongation, both changes resulting in hyperopia. The refractive error after 5 days of lens wear correlated well with vitreous chamber depth, which reflected the changes in both choroidal thickness and ocular length. The degree of compensation for lenses was not affected by whether the fellow eye was covered or open. Both form-deprivation myopia and lens-induced myopia declined with age in parallel, but wearing a -15 D lens produced more myopia than did form deprivation. The spectacle lenses affected the refractive error not only of the lens-wearing eye, but also, to a much lesser degree, of the untreated fellow eye. At lens removal refractive errors were opposite in sign to the lense worn, and the subsequent changes in choroidal thickness and ocular length were also opposite to those that occurred when the lenses were in place. In this situation as well, effects of the spectacle lenses on the fellow eyes were observed. Eyes with no functional afferent connection to the brain because of either prior optic nerve section or intraocular tetrodotoxin injections showed compensatory changes to imposed defocus, but these were limited to compensation for imposed myopic defocus, at least for the eyes with optic nerve section. In addition, optic nerve section, but not tetrodotoxin treatment, moved the set-point of the visual compensatory mechanism toward hyperopia. Optic nerve section prevents myopia in response to negative lenses but not to diffusers, suggesting that compensation for hyperopia requires the central nervous system.

Moving the Retina: Choroidal Modulation of Refractive State

The chick eye is able to change its refractive state by as much as 7 D by pushing the retina forward or pulling it back; this is effected by changes in the thickness of the choroid, the vascular tissue behind the retina and pigment epithelium. Chick eyes first made myopic by wearing diffusers and then permitted unrestricted vision developed choroids several times thicker than normal within days, thereby speeding recovery from deprivation myopia. Choroidal expansion does not occur when visual cues are reduced by dim illumination during the period of unrestricted vision. Furthermore, in chick eyes presented with myopic or hyperopic defocus by means of spectacle lenses, the choroid expands or thins, respectively, in compensation for the specific defocus imposed. Consequently, when the lenses are removed, the eye finds its refractive error suddenly of opposite sign, and the choroidal thickness again compensates by changing in the opposite direction. If a local region of the eye is made myopic by a partial diffuser and then given unrestricted vision, the choroid expands only in the myopic region. Although the mechanism of choroidal expansion is unknown, it might involve either a increased routing of aqueous humor into the uveoscleral outflow or osmotically generated water movement into the choroid. The latter is compatible with the increased choroidal proteoglycan synthesis either when eyes wear positive lenses or after diffuser removal.

Developmental aspects of experimental myopia in chicks: Susceptibility, recovery and relation to emmetropization

Chicks deprived of form-vision in the lateral part of their visual fields become severely myopic largely because of elongation of the vitreous chamber. The myopia mostly affects the visually deprived nasal retina; the nondeprived temporal retina is unaffected. These changes occur most rapidly early in life, being evident then after only 3 days of visual restriction. The susceptibility declines with age, being proportional to the rate of increase of axial length. Recovery from this myopia occurs if the visual restriction is removed during the first 6 weeks of life, as a result of the cessation of elongation of the vitreous chamber. The rate of recovery is directly related to the degree of myopia and inversely related to age. The pattern of changes in refractive status and variability argue for the probable existence of an active mechanism regulating eye growth in a manner dependent on refractive error, thereby producing emmetropization.

Visual deprivation causes myopia in chicks with optic nerve section

Deprivation of form vision restricted to a region of the retina produces myopia and axial elongation only in that region. We asked whether this control of eye growth by the presence or absence of visual stimuli might take place entirely within the eye. Chicks with neonatal optic nerve section, wearing an occluder that deprived one half of the retina of form vision, had vitreous chamber elongation and myopia both restricted to the deprived region. Chicks with optic nerve section but without occluders had eyes smaller than normal with severe hyperopia. These results suggest that two different mechanisms may control eye growth, one within the eye and the other in the brain.

The regulation of eye growth and refractive state: An experimental study of emmetropization

During growth the vertebrate eye achieves a close match between the power of its optics and its axial length with the result that images are focused on the retina without accommodative effort (emmetropia). The possibility that vision is required for the regulation of eye growth was studied experimentally in chicks made myopic or hyperopic by different visual manipulations. After discontinuing these visual manipulations, the eyes returned quickly to emmetropia mainly by adjusting the growth of their vitreous chambers; growth stopped in eyes recovering from myopia and continued in eyes recovering from hyperopia. Because both hyperopic and myopic eyes were already larger than normal controls, the difference in growth indicates that refractive error, rather than eye size per se, guides the eye toward emmetropia. Evidence is also presented for nonvisual shape-related control of eye growth, but this is slow-acting and cannot explain the emmetropization from induced refractive errors. Both the visually guided and shape-related mechanisms work even in eyes with the optic nerve cut, indicating that the two mechanisms are local to the eye. Although the optic-nerve-sectioned eye can sense the sign of a refractive error and initially adjust growth accordingly, it eventually overshoots emmetropia and reverses the sign of the initial refractive error. Whether this is due to loss of feedback from the central nervous system or retinal ganglion cells is unclear.

Developing eyes that lack accommodation grow to compensate for imposed defocus.

The eyes of growing chicks adjust to correct for myopia (eye relatively long for the focal length of its optics) or hyperopia (eye relatively short for the focal length of its optics). Eyes made functionally hyperopic with negative spectacle lenses become myopic and long, whereas eyes made functionally myopic with positive spectacle lenses become hyperopic and short. We report here that these compensatory growth adjustments occur not only in normal eyes but also in eyes unable to accommodate (focus) because of lesions to the Edinger-Westphal nuclei. Thus, at least in chicks, accommodation is not necessary for growth that reduces refractive errors during development, and may not be necessary for the normal control of eye growth.

Accessory optic system and pretectum of birds: comparisons with those of other vertebrates.

We compare the functional and anatomical organization in birds and other vertebrates of the accessory optic nuclei and of those pretectal nuclei implicated in optokinetic responses. In all vertebrate groups, the neurons in these nuclei respond most strongly to slow large-field visual motion in particular directions; the several nuclei differ in the direction of stimulus motion that evokes the best response. These nuclei are essential for optokinetic nystagmus (OKN) in all species examined; the pretectum is necessary for horizontal OKN and the accessory optic nuclei for OKN in other directions. At least in the accessory optic system of birds, the directional parcellation is not well-developed at hatching and requires visual experience to develop normally. There is evidence that the accessory optic system may play a role in transforming the visual motion signal from retinal coordinates into vestibular or oculomotor coordinates. In regard to anatomical connections, in all vertebrate groups studied, the accessory optic and pretectal nuclei project either directly or indirectly to the cerebellum; in addition, the accessory optic system and pretectum are extensively reciprocally connected. In some groups, but not in others, projections have been discovered from the accessory optic system and pretectum to the extraocular motor nuclei and from the accessory optic system to both the vestibular complex and the interstitial nucleus of Cajal.

Temporal constraints on lens compensation in chicks.

If the effective focal length of a growing eye is modified by spectacle lenses, the eye compensates by altering its growth, thereby keeping images in focus, a process we presume is similar to normal emmetropization. Using chicks, we have investigated how much visual exposure the eye needs to exhibit the two principal components of ocular compensation: altered rate of elongation (a scleral mechanism) and altered choroidal thickness. We have found that surprisingly small amounts of vision through spectacle lenses can elicit robust scleral and choroidal compensation if other visual feedback is limited by keeping the animals in the dark when not wearing lenses. Furthermore, we have found that the amount of vision necessary to induce these responses can be summarized as three rules: First, several brief daily episodes are more effective than a single or a few longer daily episodes, even if the total amount of vision is the same. Second, extremely brief episodes, even if very frequent, are relatively ineffective. Third, when plus and minus lenses are worn successively on the same eye, the plus lens has the dominant effect, even if the minus lens is worn five times longer than the plus lens. In addition, we have shown that the elongation rate and choroidal thickness responses are dissociable, such that brief, infrequent lens-viewing produces only an elongation response in the case of plus lens-wear and only a choroid response in the case of minus lens-wear. We thus show that the emmetropization system does not integrate defocus in a simple, linear fashion. These non-linearities, if present in children, might explain why, although education and reading show an epidemiological correlation with myopia, the total time spent reading and doing other nearwork by individual children generally does not predict the degree of myopia. It may therefore be necessary to quantify more complex temporal patterns of nearwork over the day in order to measure the impact of nearwork on eye growth.

Relation of Single Unit Properties to the Oculomotor Function of the Nucleus of the Basal Optic Root (Accessory Optic System) in Chickens

SummarySingle unit recordings in the nucleus of the basal optic root (nBOR) of the accessory optic system in chickens suggest that it has a role in vertical stabilizing eye movements. Cells have unusually large receptive fields and never respond to small stationary stimuli. They respond best to large richly patterned stimuli moving slowly (2–4 °/s) in vertical directions. Cells responsive to upward movement tend to be located in the dorsal portion of nBOR, which projects to motor areas producing upward eye movement, whereas cells responsive to downward movement tend to be located in the ventral portion of nBOR, which projects to motor areas producing downward eye movement; this suggests that these synapses onto oculomotor neurons are excitatory.In many nBOR units, the preferred and null directions are not opposite to each other. These directional asymmetries seem to be correlated with other properties of the units in a manner that supports the idea that the accessory optic system is arranged according to a vestibular coordinate system. This finding complements the abundant anatomical and physiological evidence linking the accessory optic system to the vestibular system.