Effects of Abnormal Visual Experience on the Retinogeniculocortical Pathway
Abnormal visual experience resulting from visual deprivation, anisometropia, or strabismus can powerfully affect retinogeniculocortical development. In studies of baby macaque monkeys, single-eyelid suturing usually produces axial myopia but no other significant anatomical changes in the eye. The lateral geniculate laminae that receive input from the deprived eye experience minor shrinkage, but these cells respond rapidly to visual stimulation, suggesting that a defect in the lateral geniculate body is not likely to account for amblyopia. In the striate cortex, monocular visual deprivation causes the regions of the visual cortex driven predominantly by the closed eye (ocular dominance columns) to radically narrow (Fig 5-2). This occurs because the 2 eyes compete for synaptic contacts in the cortex. As a result, the deprived eye loses many of the connections already formed at birth with postsynaptic cortical targets. The open eye profits by the sprouting of terminal arbors beyond their usual boundaries to occupy territory relinquished by the deprived eye (Fig 5-3). However, the benefit derived from invading the cortical territory of the deprived eye is unclear because visual acuity does not improve beyond normal. Positron emission tomography has shown that cortical blood flow and glucose metabolism are lower during stimulation of the amblyopic eye compared with the normal eye, suggesting the visual cortex as the primary site of amblyopia. Monocular deprivation also devastates binocularity because few cells can be driven by both eyes.
Figure 5-2 Change in ocular dominance columns in macaque visual cortex after monocular deprivation. Radioactive proline was injected into the normal eye and transported to the visual cortex to reveal the projections of that eye. In these sections, cut parallel to the cortical surface, white areas show labeled terminals. A, Normal monkey. There is roughly equal spacing of the stripes, which represent the injected eye (bright) and noninjected eye (dark).B, Monkey that had 1 eye sutured closed from birth for 18 months. The bright stripes (open, injected eye) are widened and the dark ones (closed eye) are greatly narrowed, showing the devastating physical effect of deprivation amblyopia. (Scale bar = 1 mm.)
(Reproduced with permission from Kaufman PL, Alm A. Adler’s Physiology of the Eye. 10th ed. St Louis: Mosby; 2002:699. Originally from Hubel DH, Wiesel TN, LeVay S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc Lond B Biol Sci. 1977;278(961):377–409.)
There is a critical period in which visual development in the macaque is vulnerable to the effects of eyelid suturing. This period corresponds to the stage in which wiring of the striate cortex is still vulnerable to the effects of visual deprivation. During the critical period, the deleterious effects of suturing the right eyelid, for example, are correctable by reversal—that is, opening the sutured right eye and closing the left eye. After this reversal, the ocular dominance columns of the initially closed right eye appear practically normal, indicating that anatomical recovery of the initially shrunken columns was induced by opening the right eye and closing the left eye. However, when the right eye is sewn closed beyond the critical period, the columns of the right eye do not re-expand if the right eye is opened and the left eye closed.
Eyelid suturing in the baby macaque is a good model for visual deprivation amblyopia. In children, this condition can be caused by any dense opacity of the ocular media or occlusion by the eyelid. Visual deprivation can rapidly cause profound amblyopia.
There are other causes of amblyopia in children. Optical defocus resulting from anisometropia causes the cortical neurons driven by the defocused eye to be less sensitive (particularly to higher spatial frequencies, because they are most affected by blur) and to send out a weaker signal. This results in reduced binocular activity. The critical period for anisometropic amblyopia occurs later than that for strabismic amblyopia, and a prolonged period of unilateral blur is necessary before anisometropic amblyopia develops. Meridional (astigmatic) amblyopia does not develop during the first year of life and may not develop until age 3 years.
Figure 5-3 Anatomical and physiologic maturation of ocular dominance columns of the primary visual cortex in normal and deprived monkeys. Birth: Broad overlap of afferents from the lateral geniculate nucleus, hence little dominance by right eye (RE) versus left eye (LE). Normal 6-month-old: Regression of overlapping afferents from both eyes with distinct areas of monocular dominance. The bar graph shows the classic U-shaped distribution obtained by single-cell recordings from the visual cortex. About half the cells are driven predominantly by the right eye and the other half by the left eye. A small number are driven equally by the 2 eyes. 1 = driven only by right eye; 2–6 = driven binocularly; 7 = driven only by left eye. Strabismus: Effect of artificial eye misalignment in the neonatal period on ocular dominance. The monkey alternated fixation (no amblyopia) and lacked fusion. Lack of binocularity is evident as exaggerated segregation into dominance columns. The bar graph shows the results of single-cell recordings obtained from this animal after age 1 year. Almost all neurons are driven exclusively by the right or left eye, with little binocular activity. Amblyopia: Effect of suturing the left eyelid shut shortly after birth. Dominance columns of the normal right eye are much wider than those of the deprivationally amblyopic left eye. The bar graph shows markedly skewed ocular dominance and little binocular activity.
(Modified with permission from Tychsen L. Binocular vision. In: Hart WM, ed. Adler’s Physiology of the Eye: Clinical Application. 9th ed. St Louis: Mosby; 1992:810.)
Strabismus can be artificially created in monkeys by the sectioning of an extraocular muscle. Alternating fixation develops in some monkeys after this procedure; they maintain normal acuity in each eye. Examination of the striate cortex reveals cells with normal receptive fields and an equal number of cells responsive to stimulation of either eye. However, the cortex is bereft of binocular cells (see Fig 5-3). After 1 extraocular muscle is cut, some monkeys do not alternately fixate; instead, they constantly fixate with the same eye, and amblyopia develops in the deviating eye. An important factor in the development of strabismic amblyopia is interocular suppression due to uncorrelated images in the 2 eyes. Strabismus prevents synchronous attainment of correlated images from the 2 foveae, resulting in abnormal input to the striate cortex. Another factor is the optical defocus of the deviated eye. The dominant eye is focused on the object of regard, while the deviated eye is oriented in a different direction; for the deviated eye, the object may be too near or too far to be in focus. Either mechanism can cause asynchrony or inhibition of 1 set of signals in the striate cortex. The critical period for development of strabismic amblyopia begins at approximately 4 months of age, during the time of ocular dominance segregation and sensitivity to binocular correlation.
Abnormal sensory input alone is sufficient to alter the normal anatomy of the visual cortex. Other areas of the cerebral cortex may also depend on sensory stimulation to form the proper anatomical circuits necessary for normal adult visual function, underscoring the importance of providing children with a stimulating sensory environment.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.