Sally A. McFadden

Retinoic acid signals the direction of ocular elongation in the guinea pig eye

A growing eye becomes myopic after form deprivation (FD) or compensates for the power and sign of imposed spectacle lenses. A possible mediator of the underlying growth changes is all-trans retinoic acid (RA). Eye elongation and refractive error (RE) was manipulated by raising guinea pigs with FD, or a spectacle lens worn on one eye. We found retinal-RA increased in myopic eyes with accelerated elongation and was lower in eyes with inhibited elongation. RA levels in the choroid/sclera combined mirrored these directional changes. Feeding RA (25 mg/kg) repeatedly to guinea pigs, also resulted in rapid eye elongation (up to 5 times normal), and yet the RE was not effected. In conclusion, RA may act as a signal for the direction of ocular growth.

Form-deprivation myopia in the guinea pig (Cavia porcellus)

Form deprivation (FD) was induced in 61 guinea pigs with a diffuser worn on one eye. The form-deprived eye elongated and developed myopia within 6 days in animals raised under a 12:12 h light/dark cycle, but not when reared in darkness. After 11 days of FD, the average eye was -6.6 D more myopic and 146 microm longer than its fellow eye. Initially the myopia was mostly from vitreous chamber elongation, but with longer periods of FD, corneal power increases predominated. These effects were confirmed in schematic eyes. After a delay, FD also elongated the vitreous chamber of the non-deprived eye. The myopia rapidly abated once the diffusers were removed (65% within 24 h) due to inhibition of elongation and choroidal thickening. The guinea pig provides a fast mammalian model of FD myopia and corneal curvature regulation.

Spectacle lens compensation in the pigmented guinea pig.

When a young growing eye wears a negative or positive spectacle lens, the eye compensates for the imposed defocus by accelerating or slowing its elongation rate so that the eye becomes emmetropic with the lens in place. Such spectacle lens compensation has been shown in chicks, tree-shrews, marmosets and rhesus monkeys. We have developed a model of emmetropisation using the guinea pig in order to establish a rapid and easy mammalian model. Guinea pigs were raised with a +4D, +2D, 0D (plano), -2D or -4D lens worn in front of one eye for 10 days or a +4D on one eye and a 0D on the fellow eye for 5 days or no lens on either eye (littermate controls). Refractive error and ocular distances were measured at the end of these periods. The difference in refractive error between the eyes was linearly related to the lens-power worn. A significant compensatory response to a +4D lens occurred after only 5 days and near full compensation occurred after 10 days when the effective imposed refractive error was between 0D and 8D of hyperopia. Eyes wearing plano lenses were slightly more myopic than their fellow eyes (-1.7D) but showed no difference in ocular length. Relative to the plano group, plus and minus lenses induced relative hyperopic or myopic differences between the two eyes, inhibited or accelerated their ocular growth, and expanded or decreased the relative thickness of the choroid, respectively. In individual animals, the difference between the eyes in vitreous chamber depth and choroid thickness reached +/-100 and +/-40microm, respectively, and was significantly correlated with the induced refractive differences. Although eyes responded differentially to plus and minus lenses, the plus lenses generally corrected the hyperopia present in these young animals. The effective refractive error induced by the lenses ranged between -2D of myopic defocus to +10D of hyperopic defocus with the lens in place, and compensation was highly linear between 0D and 8D of effective hyperopic defocus, beyond which the compensation was reduced. We conclude that in the guinea pig, ocular growth and refractive error are visually regulated in a bidirectional manner to plus and minus lenses, but that the eye responds in a graded manner to imposed effective hyperopic defocus.

Emmetropization and schematic eye models in developing pigmented guinea pigs

A model of the axial change in ocular parameters of the guinea pig eye from 2 to 825 days of age was developed and a corresponding paraxial schematic eye model applicable from 2 to 100 days of age was constructed. Axial distances increased logarithmically over time except for the lens in which growth was more complex. Over the first 30 days, ocular elongation was approximately linear: ocular length increased by 37 microm/day, the majority due lens expansion. The choroid and sclera thickened with age, while the retina thinned in proportion to the increased ocular size, and the model suggests that there is no small eye artefact for white light retinoscopy. Refractive error just after birth was +4.8D but halved within the first week. Emmetropization occurred within the first month of life similar to that in other species when aligned at the point of sexual maturity and scaled by the time taken to reach adulthood. The power of the eye was 227D at 2 days of age and reduced by 19.7D by 100 days due to a 22% decrease in the power of the cornea. The posterior nodal distance (PND) was 4.7 mm at 30 days of age, with a maximum rate of change of 13 microm/day during the first week. The ratio of PND to axial length declined until at least 100 days of age, well after emmetropia was reached. This suggests that the maintenance of emmetropia is not sustained through proportional axial growth, but involves some active mechanism beyond simple scaling. The model predicts that 1D of myopia requires an elongation of between 23 and 32 microm, depending upon age, suggesting that a resolution of at least 50 microm is required in methods used to determine the significance of ocular length changes in guinea pig models of refractive development. Retinal magnification averaged 80 microm/degree, and the maximum potential brightness of the retinal image was high, which together with a ratio of lens power to corneal power of 1.7-2.0 suggests that the guinea pig eye is adapted for nocturnal conditions.

Monkey eyes grow into focus.

Previous studies that suggested that lens-wearing may affect eye growth are supported now by primate studies, which raises questions about the use of eyeglasses in children (pages 761–765).

Binocular Depth Perception

Successfully negotiating any spatial environment requires two distinct but related forms of visual information. The first is absolute distance information, which allows an animal to “know” its position with respect to other objects or points in space (e.g. D in Fig. 3.1). This is sometimes referred to as egocentric (self-centred) distance perception. It allows visual information to be used for precise motor action. The second form of spatial perception, depth perception, provides information regarding the relative position of two or more objects (e.g. d in Fig. 3.1). It is distinct from absolute distance perception in that it gives no information regarding the distance of the comparison points from the observer. What then is its use? It is argued in this chapter that such relative distance or depth perception is essential for complex object detection, but can only be used to guide reaching motor movements in the limiting case where one of the reference points (e.g. F or P in Fig. 3.1) is always at some predetermined absolute distance.

A pharmacological approach to first aid treatment for snakebite.

Snake venom toxins first transit the lymphatic system before entering the bloodstream. Ointment containing a nitric oxide donor, which impedes the intrinsic lymphatic pump, prolonged lymph transit time in rats and humans and also increased rat survival time after injection of venom. This pharmacological approach should give snakebite victims more time to obtain medical care and antivenom treatment.

A further look at the binocular visual field of the pigeon (Columba livia)

The binocular visual field of the pigeon, measured ophthalmoscopically, is ovoid in shape. It is 114 degrees in vertical extent and centered and widest (37 degrees) about the eye-beak axis (i.e. the line passing through the straight edge of the beak and the midpoint of a line connecting the centres of the pupils). The area dorsalis projects 10 degrees-15 degrees below the eye-beak axis where the field is 35 degrees wide. The stereotyped peck response of the pigeon entails birds pausing twice. At the first fixation, the image of a grain is on the area dorsalis and at the final fixation the grain is centered within the widest part of the binocular field.

Gain adaptation of exogenous shifts of visual attention.

Gain adaptation of saccadic eye movements is the process whereby the size of the saccade is gradually modified if the target is consistently and surreptitiously displaced during the saccade. Because one attends to the saccade target before each saccade, we asked whether covert shifts of exogenous attention might themselves be adaptable. We did this by presenting a peripheral cue and then displacing it by 3 deg after an interval equal to the average time required for attention to shift from a central to a peripheral cue. This interval, as well as the location at which attention landed, was determined by a modification of the line-motion illusion, in which a line appears to shoot from a previously cued location. We found that this adaptation paradigm produced consistent gradual reductions (for back-steps) or increases (for forward-steps) in the magnitude of the shifts of attention. Like saccadic adaptation, adaptation of shifts of attention could be manipulated independently for rightward and leftward shifts. Furthermore, the backward adaptation paradigm also decreased the magnitude of subsequent saccades, even though no saccades had been made during the attentional adaptation. This argues that saccades are targeted to the locus of attention, and when this locus is systematically shifted, so too are subsequent saccades. In conclusion, the adaptability of shifts of attention suggests that attentional shifts, like saccades, are recalibrated using a spatial error signal.

Integration of defocus by dual power Fresnel lenses inhibits myopia in the mammalian eye.

PURPOSE Eye growth compensates in opposite directions to single vision (SV) negative and positive lenses. We evaluated the response of the guinea pig eye to Fresnel-type lenses incorporating two different powers. METHODS A total of 114 guinea pigs (10 groups with 9-14 in each) wore a lens over one eye and interocular differences in refractive error and ocular dimensions were measured in each of three experiments. First, the effects of three Fresnel designs with various diopter (D) combinations (-5D/0D; +5D/0D or -5D/+5D dual power) were compared to three SV lenses (-5D, +5D, or 0D). Second, the ratio of -5D and +5D power in a Fresnel lens was varied (50:50 compared with 60:40). Third, myopia was induced by 4 days of exposure to a SV -5D lens, which was then exchanged for a Fresnel lens (-5D/+5D) or one of two SV lenses (+5D or -5D) and ocular parameters tracked for a further 3 weeks. RESULTS Dual power lenses induced an intermediate response between that to the two constituent powers (lenses +5D, +5D/0D, 0D, -5D/+5D, -5D/0D and -5D induced +2.1 D, +0.7 D, +0.1 D, -0.3 D, -1.6 D and -5.1 D in mean intraocular differences in refractive error, respectively), and changing the ratio of powers induced responses equal to their weighted average. In already myopic animals, continued treatment with SV negative lenses increased their myopia (from -3.3 D to -4.2 D), while switching to SV positive lenses or -5D/+5D Fresnel lenses reduced their myopia (by 2.9 D and 2.3 D, respectively). CONCLUSIONS The mammalian eye integrates competing defocus to guide its refractive development and eye growth. Fresnel lenses, incorporating positive or plano power with negative power, can slow ocular growth, suggesting that such designs may control myopia progression in humans.