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Hatchling chicks reared with defocusing spectacle lenses compensate for the applied defocus, both refractively and through changes in eye growth, in about 1 week. In this experiment, we show that pharmacological inhibition of the retinal ON or OFF responses to light stimulation with isomers of alpha-aminoadipic acid results in a sign-dependent pattern of interference with the refractive compensation mechanism. An intravitreal injection of 2.5 microM L-alpha-aminoadipic acid inhibited the ERG ON response and inhibited refractive compensation to negative lens defocus, but not to positive or zero power lens defocus. D-alpha-aminoadipic acid in the same dose reduced the retinal OFF response and inhibited refractive compensation to positive lens defocus, but not to negative or zero power lenses. Thus the pharmacological manipulation of induced refractive change suggests that the retinal ON and OFF subsystems play independent roles in the emmetropization process.

A 35-year-old woman who reported persistent significant vision loss for 3 years after taking the antidepressant nefazodone was referred for electrophysiological assessment of vision. The vision changes included reduced acuities, reduced colour vision and visual field constriction in both eyes and were thought to be associated with the use of nefazodone for 6 - 8 weeks, 3 years earlier. Multifocal electroretinograms and visual evoked potentials were recorded using the Visual Evoked Response Imaging System (VERIS) to investigate the nature and site of the neural deficit. The summed retinal response showed a normal a- and b-wave latency and amplitude, however, the retinal topographic mfERGs showed a severe depression of the macular response in both eyes. The cortical topographic multifocal VEP mapping also showed a central depression in the right eye compared with the left. Two-frame motion and pattern custom mfVEP were also measured to assess different forms of cortical processing and especially of motion as nefazodone has previously been associated with image persistence with moving stimuli. The responses to two frame-motion showed signs of abnormality. Thus these results suggest that the primary locus of neural damage is retinal and is likely to have resulted from neurotoxicity. Other competing hypotheses such as hysterical blindness must be ruled out.

The refractive state of hatchling chicks rapidly compensates to applied optical defocus through alteration in eye growth. The mechanism is capable of sensing whether the plane of focus lies in front of or behind the photoreceptors, however, its nature and site of action within the retina are unknown. We attempted to create an imbalance in the adaptation of the retinal ON and OFF mechanisms previously implicated in refractive control through pharmacological interventions, by rearing chicks from 4 to 9 days of age with a monocular +10 D, 0 D or -10 D lens, in an environment illuminated by a moving or stationary plaid of luminance gradients. When the plaid moved in one direction a local Fast-ON sawtooth luminance modulation was produced, while plaid motion in the other direction resulted in a Fast-OFF sawtooth modulation. Significantly reduced refractive compensation accompanied +10 D lens/Fast-OFF and -10 D lens/Fast-ON rearing, but not for the other conditions. Thus the refractive compensation mechanism depends on the nature of the temporal contrast of the environment, suggesting a relationship between the sign of defocus and the state of adaptation of the retinal ON and OFF subsystems.

Purpose: Simultaneous comparisons of the circumferential morphological tissue profiles and final refractions from form-deprivation myopia (FDM), defocus-induced myopia (DIM), and defocus-induced hyperopia (DIH) models of ametropia have been made to test the hypothesis that changes in the thickness profiles of the three coats of the eye, and particularly that of the choroid, can be predicted from the degree of induced refractive error., Methods: Hatchling chickens (n = 23) were raised for 2 weeks wearing either a monocular translucent diffuser (FDM, n = 8), monocular -10.00 D lens goggle (DIM, n = 7), monocular +10.00 D lens goggle (DIH, n = 7), or nothing (Norm, n = 1). All animals were refracted using retinoscopy and were then sacrificed, and whole eyes were processed for scanning electron microscopy. Retinal, choroidal, and cartilaginous sclera (CS) thickness measurements were made from photographic collages of the entire circumference of the globe. Of the 23 chickens, complete morphological profile data were available for both eyes of 10 animals (nine treated and one normal). The contralateral fellow eyes (FEyes) of all nine experimental chickens were used as experimental controls as paired comparisons for statistical analyses., Results: Morphological profiles of control and experimental eyes revealed significant systematic regional variations in tissue thickness. This variation was related to nasal or temporal eccentricity with the nasal side generally thinner than the temporal. Retinal, choroidal, and CS tissue from FDM and DIM eyes showed very similar anatomical responses despite significantly different degrees of refractive change. DIH eyes showed significant increases in choroidal thickness but none in retinal or CS thickness. Analysis of fellow control eyes indicated that in both myopia models (FDM and DIM), significant changes in all tissues of the untreated fellow eyes occur whereas only the choroid of the fellow eye was affected in the hyperopic (DIH) model., Conclusions: The morphological similarity observed in the circumferential profiles of the retina, choroid, and cartilaginous sclera of the FDM and DIM eyes despite approximately 20 D difference in final refraction suggests that choroidal thickness is not a good predictor of final refractive error across models. Similarly, the final refractive difference of approximately 20 D between the DIM and the DIH eyes did not receive a major contribution from the final difference in choroidal thickness (with its implied effect on vitreous chamber length).

The aim of the current study was to develop a method for simultaneously assessing central and peripheral photoreceptor alignment in vivo in animal models. The stimulus apparatus consisted of nine light-emitting diodes (LED) positioned 7.5 degrees apart around an arc. The stimulus was viewed through a pinhole imaged into the entrance pupil of the eye using a telecentric lens system. Photodiodes placed over an array of the VERIS imaging system stimulated the electroretinogram. Data were obtained by positioning the pinhole at 0.25-mm intervals across the pupil and recording (Volk Optical, Mentor, OH, USA) at each location. Orientation assessed in normal chickens demonstrates that photoreceptors orientate towards a locus near the centre of the pupil and that there is a systematic change in peak location with eccentricity. This technique provides a valuable method for determining photoreceptor orientation properties in vivo and can be applied to animal models of pathology.

Purpose: The present study compares morphological changes associated with optical defocus-induced myopia (ODM) with those from form deprivation myopia (FDM), as it is yet to be determined whether the latter is a consequence of visual deprivation or active myopic eye growth., Methods: Hatchling chicks were reared for 2 weeks wearing a monocular translucent occluder or -10.00 D lens, with the other eye used as a control. After enucleation, eyes were processed for scanning electron microscopy., Results: Anatomical profiles of control eyes revealed significant variations in tissue thickness as a function of nasotemporal location. Both FDM and ODM eyes demonstrated similar morphological profiles of retinal thinning, cartilaginous scleral thickening, enlarged photoreceptor inner segments and decreased photoreceptor cell density towards the ora serrata. A graded differential orientation of photoreceptors existed in all eyes., Conclusion: The comparable morphological changes in FDM and ODM suggest that the response to altered visual experience is similar in both paradigms.

The topographic electroretinogram evoked by multi-focal exchange of black and white or red and green stimuli was analysed into linear and non-linear Wiener kernels. The first-order (temporally linear) response showed a biphasic waveform which inverted as the luminance ratio of the exchanged colours passed through unity (established both psychophysically and photometrically). A short latency non-linearity which was dependant on luminance contrast was observed in both chromatic and achromatic ERG. However, in the chromatic second-order response, a long-latency non-linearity, foveally prominent, with a distinct skew in power towards the nasal retina, appeared around the isoluminant point, between the points of silent substitution for the L and M-cone types. Modelling of the second-order responses showed that over a wide range of luminance ratios, the chromatic ERG is well described by a linear combination of the achromatic (contrast-dependent) component and the response at isoluminance. The difference in second-order response between coloured and black and white stimulation, at the same luminance contrast, showed that the long-latency non-linearity is recorded when the red and green cone types are operating out of phase and peaks in amplitude at a green/red luminance ratio of 0.8. This interpretation was confirmed by the lack of the long-latency non-linearity in colour-anomalous subjects (whether deficient in the L or the M-cone type). A marked similarity exists between the properties of the long-latency non-linearity and the frequency-doubled response generated in the ganglion cells of the magnocellular pathway.

The interaction between drugs which affect ON and OFF responses to light and ocular growth was investigated in 154 eyes of newly-hatched chicks raised with normal vision or monocular occlusion with regular intravitreal injections of APB (2-amino-4 phosphonobutyric acid) or PDA (cis 2,3-piperidine-dicarboxylic acid). The experimental results indicate that APB, at a dose sufficient to abolish the b-wave of the electroretinogram (but not to show extensive damage to the retinal neurons at the light microscopic level), caused a significant decrease in the axial growth of the eyes when compared with normal eyes. APB did not result in a significant difference in the growth rates of the occluded eyes compared with occluded controls. By contrast, injection of PDA into occluded eyes at a dose which reduced the response at light offset in the electroretinogram (and also affected the ON-response), caused a dramatic reduction in elongation of those eyes compared with occluded controls. Injection of PDA into eyes raised in a normal visual environment did not induce a significant difference from the growth rate of normally reared control eyes. These growth changes support the hypothesis that drugs which affect the physiological function of the retina, in particular, the strength of the ON and OFF responses, interact with the visual rearing environment to cause a consistent pattern of changes to eye growth and refractive error.

Twenty hatchling chickens were injected intravitreally every 4 days from day 2 to day 16 with dimethyl sulphoxide (DS) in one eye and DS or formoguanamine dissolved in DS (FG.DS) with or without occlusion in the other (FG.DS.MD, DS.MD, FG.DS). At day 16, the FG.DS.MD eyes failed to show the high refractive myopia and showed less axial elongation than that developed by the DS.MD eyes. Electroretinograms indicated that at the dosage used, FG.DS does not eliminate phototransduction. Light microscopy showed choroidal and retinal thinning in DS.MD and FG.DS.MD eyes but less than in FG.DS eyes, suggesting that change in choroidal thickness is unlikely to be the primary cause of form deprivation myopia.

The acuities of cells in the primary visual cortex of five tenotomized strabismic cats were measured. Previous behavioural studies have shown such animals to possess a severe amblyopia of approximately 1.5 octaves of spatial frequency, yet the acuities of both retinal ganglion and lateral geniculate X-cells are normal. The receptive fields of the cortical cells sampled were within 5 degrees of the area centralis projection. On average, the acuities of cortical cells driven by the amblyopic eye were nearly 1 octave less than those for the non-deviating eye. However, the best cell acuities for each eye were nearly the same. The relationship between ocular dominance and cell acuity was found to be different for the two eyes despite a symmetrical ocular dominance distribution. The acuity deficit for cells driven through the amblyopic eye was present at all depths along the electrode tracks. We conclude that in this model amblyopia, the initial spatial processing deficit lies in the visual cortex, and most probably in the cells of layer IV. Furthermore, the presence of a few cells driven by the amblyopic eye which can perform nearly as well as those from the fellow eye in processing high spatial frequencies gives new insight into the way in which strabismic and deprivation amblyopias differ.

The pattern of retinogeniculate connections has been examined in a range of diprotodont marsupials, including wallabies, possums, forest wombat and koala. The lateral geniculate nucleus (LGd) in most species has alternating bands of ipsilateral and contralateral retinal terminal fields, with considerable interspecific variability. The number of terminal bands of retinogeniculate input varies from eight to eleven in most species, with little binocular overlap. By contrast in one species, the feather-tailed glider, the most significant feature of LGd organisation is binocular overlap. No relationship is apparent between LGd organisation and the life-style of the animals.

The spatial resolution of 87 on-centre retinal ganglion cells was measured at different retinal eccentricities in the retina of the deprived eye of two monocularly-deprived cats. Intra-ocular recording techniques were employed in order that particular attention could be placed on ganglion cells in the region of the area centralis. The spatial cut-off frequencies of both major classes on-centre ganglion cells were comparable to those observed in normal retinas at similar retinal eccentricities. In particular there was no evidence of any loss of spatial resolution of either class of cell in the vicinity of the area centralis as has been reported in the retina of the deviating eye of strabismic cats.

Behavioural estimates of the visual acuity of the Northern Native Cat (or Northern Quoll)--Dasyurus hallucatus--were made using the Mitchell jumping stand technique. A value of 2.3-2.8 cycles per degree was obtained. This functional acuity compared well with predictions based on the peak ganglion cell density (2600 cells/mm2) determined from the retinal ganglion cell density map.

1. A convergent or divergent strabismus was induced surgically in eight kittens and a cyclotropia of about 90 deg in two additional kittens. 2. Behavioural measurements were made of the visual acuity of each eye for square-wave gratings. All eight animals that were so tested displayed a reduction of acuity in one eye relative to the other of 1.3-2.5 octaves. 3. The activity of retinal ganglion cells was recorded within the amblyopic eye of six cats, three with a convergent strabismus, two with a divergent strabismus and one with a cyclotropia. Measurements were made of the spatial resolution with 215 on-centre cells for horizontal and vertical gratings. 4. In contrast to other reports, we found the spatial resolution of ganglion cells in the amblyopic eye of the strabismic animals to be comparable to those of normal cats at all retinal eccentricities. In particular there was no evidence for a loss of resolution in the vicinity of the area centralis. 5. Measurement of the cross-sectional area of cells in the lateral geniculate nucleus (l.g.n.) revealed no evidence of cell shrinkage in laminae receiving a projection from the amblyopic eye. 6. Together, these findings lead to the conclusion that the neural deficit responsible for the strabismic amblyopia in these animals did not lie in the retina but rather at more central levels of the visual pathway.

Two preparations were used to study the developmental effects of prolonged blurring of retinal images on the acuities of retinal ganglion cells. Five kittens were raised from three weeks to six months of age with daily administration of atropine to one eye. Another two kittens were raised from three weeks to 16 weeks with a contact lens of high refractive power fitted to one eye. Behavioural estimates of the visual acuity were made for two animals from each group. Animals of both groups demonstrated an amblyopia in the experimental eye: visual acuity varied from 1.8 to 2.5 cycles per degree compared with 6.0 to 7.5 cycles per degree when using the normal eye. The spatial resolving properties were measured for retinal ganglion cells within the amblyopic eyes of two lens-reared cats and three atropinized cats. Brisk-sustained (X) cells were recorded from along the naso-temporal division. The acuities of ganglion cells from the lens-reared cats were indistinguishable from those from normal cats at comparable eccentricities. However, for the cats raised with atropine administration, sub-normal acuities were determined for retinal ganglion cells from all regions that were studied in the experimental eye. We conclude that blur of retinal images produced by external means has no effect on the resolving power of retinal ganglion cells. The lowered ganglion cell acuities encountered with the atropinized cats must be attributable to a secondary effect of the atropine administration. Organic changes in the retinal blood vessel pattern support this contention.

The influence of afferent input on the survival of target neurons in mammals has been examined by the removal of one eye of pouch young of the marsupial native cat (Dasyurus hallucatus). The ages at eye removal spanned the period of neurogenesis of the ascending visual pathway, and were earlier than the time of maximal axon number in the optic nerve. Autoradiography following the injection of tritiated proline into the intact eye of adult animals shows that the lateral geniculate nucleus contralateral to the injected eye of the earliest enucleates retains its laminated structure, despite the total absence of binocular competition throughout development. However, we find a dramatic, age-related reduction in the volume of those parts of the lateral geniculate nucleus and superior colliculus which would normally receive a contralateral-only projection from the enucleated eye. The effects of the enucleation are not restricted to the primary termination sites of the optic axons but ramify throughout a large part of the neo- and archicortex.