Animal models of amblyopia (original) (raw)
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Animal models of strabismic amblyopia: Comparative behavioral studies
Behavioural Brain Research, 1983
Visual acuity and visuo-motor behavior were assessed in various models of experimental amblyopia in cats (n = 15). Three models of strabismic amblyopia were studied: surgical esotropia by sectioning one lateral rectus muscle; comitant optical strabismus by rearing cats with goggles which placed a stationary wedge prism before one eye; and incomitant optical strabismus by rearing cats with goggles which placed a rotatable wedge prism before one eye. These cats were compared with normal and monocularly deprived cats. Clear amblyopic deficits were found in monocularly deprived, esotropic and rotating prism cats. The amblyopic deficits were graded among these preparations, being most severe in monocularly deprived cats and least severe in esotropic cats. The degree of behavioral amblyopia in these preparations was correlated with the extent of physiological abnormalities in visual cortex and the lateral geniculate nucleus. Fixed optical strabismus did not result in behavioral deficits and does not appear to be a good model of strabismic amblyopia. Variable optical strabismus, on the other hand, produced clear deficits in one eye, both behaviorally and physiologically, without impaired ocular motility.
Clinical and Experimental Optometry, 2002
Objective: With the benefit of hindsight based on an additional 20 years of research, we review a question posed originally by Marg' of whether animal models for stimulus deprivation amblyopia in children are valid or useful for clinical application. Method: Following a review of relevant research on animal models, the human clinical literature on treatment of stimulus deprivation amblyopia has been reviewed with respect to past and current impact of animal research on clinical treatment. In addition, we speculate on the potential future clinical impact of animal work on developmental plasticity in the visual cortex that is directed towards an understanding of its underlying molecular basis. Conclusions: Animal research that has begun to define the timing, nature and sites of critical periods in the central visual pathways with greater precision than was known 20 years ago has had a demonstrable impact on clinical practice. In turn, these changes in clinical practice have produced far better outcomes than prior to 1980, for both the acuity of the amblyopic eye and for binocular functions such as stereopsis.
Amblyopia: New molecular/pharmacological and environmental approaches
Visual neuroscience, 2018
Emerging technologies are now giving us unprecedented access to manipulate brain circuits, shedding new light on treatments for amblyopia. This research is identifying key circuit elements that control brain plasticity and highlight potential therapeutic targets to promote rewiring in the visual system during and beyond early life. Here, we explore how such recent advancements may guide future pharmacological, genetic, and behavioral approaches to treat amblyopia. We will discuss how animal research, which allows us to probe and tap into the underlying circuit and synaptic mechanisms, should best be used to guide therapeutic strategies. Uncovering cellular and molecular pathways that can be safely targeted to promote recovery may pave the way for effective new amblyopia treatments across the lifespan.
Ophthalmology, 1978
Physiologic and anatomic evidence has suggested an anatomic disconnection between the deprived eye and visual cortical neurons in cats made amblyopic by monocular deprivation. Clinical and visual-evoked response data suggest, however, that inhibition may play a major role in amblyopia. Accordingly, we intravenously administered anti-inhibitory compounds (bicuculline, ammonium ion, naloxone) to amblyopic cats and demonstrated a substantial restoration of binocular input to the visual cortex. Such pharmacologic reversal suggests that amblyopia is not an anatomically fixed lesion. THE foundations for current investigations in visual physiology were laid by Rubel and Wiesel in the 1960s. 1-9 They were the first to describe the linear organization of receptive fields in the visual cortex and to demonstrate, in a quantitative manner, that most cortical neurons receive binocular inputs. They were the first to suggest an organizational hierarchy for the visual system where neurons with simpler
Developmental Brain Research, 1982
Receptive field properties of visual cortical and lateral geniculate cells were studied in 4 models of amblyopia in the cat: monocular deprivation (MD cats), surgical esotropia (esotropic cats), optically induced concomitant strabismus (stationary prism cats) and optically induced incomitant strabismus (rotating prism cats). Comparison observations were made in normal cats. Recordings in visual cortex indicated a reduction in responsiveness to the treated eye in MD and rotating prism cats. Esotropic and stationary prism cats showed mainly a loss of binocular cells. Recordings in the lateral geniculate nucleus indicated a reduction in the spatial resolving capacity of X-cells driven by the treated eye in MD, esotropic and rotating prism cats. The magnitude of this effect was comparable in all of these preparations. Stationary prism cats showed comparable spatial resolving capacities in X-cells drwen by either eye. Y-cells were unaffected in any preparation except MD where there were reduced frequencies of Y-cells driven by the treated eye. These results indicate that: (1) interocular differences in spatial patterns without form deprivation are sufficient to produce a loss of responsiveness to one eye in visual cortex; (2) incomitant disparities are necessary to produce the physiological correlates of amblyopia in cats; and (3) deficits in spatial resolution in geniculate neurons are comparable m magnitude in various amblyopic preparations.
The Pathophysiology of Amblyopia: Electrophysiological Studies
Annals of the New York Academy of Sciences, 1980
Functional amblyopia may be defined as a loss of visual acuity caused by form deprivation and/or abnormal binocular interaction, for which no organic cause can be detected by the physical examination of the eye.' Amblyopia is usually associated with strabismus (turned eye), anisometropia (unequal refractive error), or form deprivation early in life, and thus represents a developmental disorder. There appears to be a critical period for the development of amblyopia in humans and it may be preventable if the causative factors are discovered and eliminated within this critical period.' Interestingly, amblyopia may also be reversible much later in life.* Over the past 15 to 20 years, there has been a renewed interest in the study of amblyopia, which is in large part attributable to the single-unit studies in cats and monkeys reared with experimentally induced amblyopia. These studies have shown that normal visual experience is essential for the development and maintenance of the physiological characteristics of cells in the visual cortex, and that disruption of the normal visual process during an early period of susceptibility by light or form deprivation, strabismus, or anisometropia, may result in a marked disturbance of the physiological organization of the visual cortex, cell shrinkage in the LGN, and severe a m b l y~p i a .~-~ However, it is not clear whether strabismus and form deprivation (due to lid suture or occlusion) affect similar cell populations in the visual pathway. There is evidence that the effects of monocular lid suture are selective for the Y or transient cells," while in kittens reared with unilateral strabismus, the X or sustained cells appear to be most affected."-" Although such methods of investigation are valuable in dealing with experimental animals, studies of human amblyopia have, for the most part been restricted to psychophysics and visual evoked potentials (VEP). In humans, with naturally occurring amblyopia, the VEP is generally the only direct method available for studying cortical responses to visual stimuli and may provide a valuable tool for the assessment of visual function in amblyopia for several reasons: (1) it provides an objective measure of function which may be useful in infants and nonverbal patients; (2) it may aid in localizing function and dysfunction; (3) it may be of value in assessing prognosis and monitoring therapy; and (4) it may be helpful in bridging the gap between psychophysics and physiology. Over the past few years we have been studying the VEP of observers with naturally occurring amblyopia using luminance and pattern stimuli. The present paper reviews some of the results. LUMINANCE EVOKED POTENTIALS There have been a large number of studies of the VEP in amblyopia using unpatterned stimuli; however, the results are quite equivocal. Some investigators
Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning
Frontiers in neural circuits, 2014
Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1-5% of the total world population. Amblyopia usually derives from conditions of early functional imbalance between the two eyes, owing to anisometropia, strabismus, or congenital cataract, and results in a pronounced reduction of visual acuity and severe deficits in contrast sensitivity and stereopsis. It is widely accepted that, due to a lack of sufficient plasticity in the adult brain, amblyopia becomes untreatable after the closure of the critical period in the primary visual cortex. However, recent results obtained both in animal models and in clinical trials have challenged this view, unmasking a previously unsuspected potential for promoting recovery even in adulthood. In this context, non invasive procedures based on visual perceptual learning, i.e., the improvement in visual performance on a variety of simple visual tasks following practice, emerge as particularl...
Experimental analysis of amblyopia and strabismus
British Journal of Ophthalmology, 1974
In the past few years physiological experiments have brought us a little closer to an understanding of some forms of developmental amblyopia-deficits of visual acuity of central, not retinal, origin, which are not correctable by optical means. While amblyopia has become a catch-all term that covers the symptoms of a multitude of disorders, there are certain stereotyped experimental procedures that invariably lead to gross disturbances in the visual system. In this paper we shall describe a few of these experiments and attempt to relate them to some of the clinical origins of amblyopia in man. The cat has been the subject of a great deal of research on the development of the visual system, though it is clear that most of the observations, with some minor differences, also apply to monkeys (see von Noorden, 1974). By extrapolation, the situation is probably similar in man. Cats, monkeys, and man are all highly binocular animals. They have roughly the same amount of binocular overlap of the two visual fields, and their eyes are extremely mobile, showing disjunctive as well as conjugate movements. There is now behavioural evidence that both cats (Fox and Blake, 197i) and monkeys (Bough, I970) normally have stereoscopic vision, being able to discriminate the relative distances of objects solely on the basis of the retinal disparity of their images. Indeed, from neurophysiological experiments there is now a fair understanding of the actual neural mechanism of stereopsis.
The pattern of visual deficits in amblyopia
Journal of Vision, 2003
Amblyopia is usually defined as a deficit in optotype (Snellen) acuity with no detectable organic cause. We asked whether this visual abnormality is completely characterized by the deficit in optotype acuity, or whether it has distinct forms that are determined by the conditions ...