Early Monocular Enucleation Research Articles

Effects of early monocular enucleation on cortical spreading depression in well-nourished and malnourished adult rats.

Sensory development is a complex process that can influence physiological and pathological factors. In laterally-eyed mammals, monocular enucleation (ME) during development and the subsequent lack of external sensory stimuli can result in permanent morphological and physiological changes. Malnutrition, especially in early life, also can cause permanent morphofunctional changes due to inadequate nutrient intake in both hemispheres. This study investigated the effects of early (postnatal day 7) ME and malnutrition during the suckling period on cortical excitability in adulthood (110-140 days of life). For this, we compared the speed propagation of cortical spreading depression in the occipital and parietal cortex of malnourished and well-nourished adult rats, previously suckled small-sized litters with three pups (L3/dam) medium-sized litters with six pups (L6/dam), and large-sized litters with twelve pups (L12/dam). The CSD velocity was augmented by the ME in the contralateral side of the removed eye in the parietal and occipital cortex. These findings suggest that visual sensory input deprivation is associated with permanent functional changes in the visual pathways, which can alter cortical excitability and lead to modifications in CSD propagation.

Altered white matter structure in auditory tracts following early monocular enucleation.

Purpose: Similar to early blindness, monocular enucleation (the removal of one eye) early in life results in crossmodal behavioral and morphological adaptations. Previously it has been shown that partial visual deprivation from early monocular enucleation results in structural white matter changes throughout the visual system (Wong et al., 2018). The current study investigated structural white matter of the auditory system in adults who have undergone early monocular enucleation compared to binocular control participants. Methods: We reconstructed four auditory and audiovisual tracts of interest using probabilistic tractography and compared microstructural properties of these tracts to binocularly intact controls using standard diffusion indices. Results: Although both groups demonstrated asymmetries in indices in intrahemispheric tracts, monocular enucleation participants showed asymmetries opposite to control participants in the auditory and A1-V1 tracts. Monocular enucleation participants also demonstrated significantly lower fractional anisotropy in the audiovisual projections contralateral to the enucleated eye relative to control participants. Conclusions: Partial vision loss from early monocular enucleation results in altered structural connectivity that extends into the auditory system, beyond tracts primarily dedicated to vision.

Early monocular enucleation selectively disrupts neural development of face perception in the occipital face area

Retinoblastoma generally occurs before 5 years of age and often requires enucleation (surgical removal of one eye) of the cancerous eye. We have previously shown using behavioural methods that this disruption in binocular vision during the critical period of visual development results in impaired face perception. In this case series study, we sought to determine the underlying neural correlates of this face perception deficit by examining brain activity in regions of cortex that preferentially respond to visual images of faces and places in 6 adults who had one eye enucleated early in life due to retinoblastoma. A group of 10 binocularly-intact adult controls were recruited for comparison. Functional magnetic resonance imaging (fMRI) was conducted over two separate runs for each participant in one scanning session. Each run consisted of 6 blocks each of face, place, and object images. Region-of-interest analyses were conducted to locate face-preferential [fusiform face area (FFA), occipital face area (OFA)] and place-preferential [parahippocampal place area (PPA), transverse occipital sulcus (TOS)] regions-of-interest. Descriptive statistics are reported. Results. Enucleated adults exhibited reduced functional activation in face-preferential regions (left FFA, right OFA, left OFA), but similar activation within the face-preferential right FFA and the place-preferential regions (bilateral PPA and TOS). Conclusions. These results indicate that early monocular enucleation prevents robust development of late-maturing face processing capabilities and that this disruption is specific to face networks and not to networks supporting other visual image categories.

Monocular enucleation alters retinal waves in the surviving eye

BackgroundActivity in neurons drives afferent competition that is critical for the refinement of nascent neural circuits. In ferrets, when an eye is lost in early development, surviving retinogeniculate afferents from the spared eye spread across the thalamus in a manner that is dependent on spontaneous retinal activity. However, how this spontaneous activity, also known as retinal waves, might dynamically regulate afferent terminal targeting remains unknown.MethodsWe recorded retinal waves from retinae ex vivo using multi-electrode arrays. Retinae came from ferrets who were binocular or who had one eye surgically removed at birth. Linear mixed effects models were used to investigate the effects of early monocular enucleation on retinal wave activity.ResultsWhen an eye is removed at birth, spontaneous bursts of action potentials by retinal ganglion cells (RGCs) in the surviving eye are shorter in duration. The shortening of RGC burst duration results in decreased pairwise RGC correlations across the retina and is associated with the retinal wave-dependent spread of retinogeniculate afferents previously reported in enucleates.ConclusionOur findings show that removal of the competing eye modulates retinal waves and could underlie the dynamic regulation of competition-based refinement during retinogeniculate development.

Altered white matter structure in the visual system following early monocular enucleation.

Partial visual deprivation from early monocular enucleation (the surgical removal of one eye within the first few years of life) results in a number of long-term morphological adaptations in adult cortical and subcortical visual, auditory, and multisensory brain regions. In this study, we investigated whether early monocular enucleation also results in the altered development of white matter structure. Diffusion tensor imaging and probabilistic tractography were performed to assess potential differences in visual system white matter in adult participants who had undergone early monocular enucleation compared to binocularly intact controls. To examine the microstructural properties of these tracts, mean diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted bilaterally. Asymmetries opposite to those observed in controls were found for FA, MD, and RD in the optic radiations, the projections from primary visual cortex (V1) to the lateral geniculate nucleus (LGN), and the interhemispheric V1 projections of early monocular enucleation participants. Early monocular enucleation was also associated with significantly lower FA bidirectionally in the interhemispheric V1 projections. These differences were consistently greater for the tracts contralateral to the enucleated eye, and are consistent with the asymmetric LGN volumes and optic tract diameters previously demonstrated in this group of participants. Overall, these results indicate that early monocular enucleation has long-term effects on white matter structure in the visual pathway that results in reduced fiber organization in tracts contralateral to the enucleated eye. Hum Brain Mapp 39:133-144, 2018. © 2017 Wiley Periodicals, Inc.

Asymmetric optic tracts in a case of unilateral isolated clinical anophthalmia—A rare case report and review of literature

Anophthalmia is a rare anomaly, the prevalence being around 3 in 100,000. It is defined as the absence of ocular tissue in the orbit. It can be seen in isolation or as part of a syndrome (in 1/3rd of cases) and can be unilateral or bilateral. Clinical anophthalmia is a term used to describe cases where the orbit seems to have no eyeball but histological studies may show evidence of ocular remnants. The present study reports the gross anatomical findings in a very rare case of unilateral and isolated anophthalmia of the right side. Despite the fact that the individual had only a rudimentary right optic nerve, an optic chiasm was developed and optic tracts were seen, but, interestingly, were asymmetric in the thickness, in such a manner that the right optic tract had increased thickness than the left optic tract. The details of the findings, with a brief review of anophthalmia and the mechanisms related to the morphogenesis of the chiasm and optic neural pathways are discussed. The exact embryogenesis of the pattern described in this case report is not clear, but this report will have implications in studies of axonal guidance and development of visual apparatus. A similar appearance has been reported in a follow up MRI study of early monocular enucleation in unilateral retinoblastoma cases, but the occurrence of asymmetric optic tracts in a case of unilateral anophthalmia is, to the best knowledge of the authors, a new finding in a very rare congenital anomaly.

DTI reveals asymmetry in the optic radiations following early monocular enucleation

DTI reveals asymmetry in the optic radiations following early monocular enucleation

Prevalence of supernumerary teeth in North Indian population: A radiological study

Anophthalmia is a rare anomaly, the prevalence being around 3 in 100,000. It is defined as the absence of ocular tissue in the orbit. It can be seen in isolation or as part of a syndrome (in 1/3rd of cases) and can be unilateral or bilateral. Clinical anophthalmia is a term used to describe cases where the orbit seems to have no eyeball but histological studies may show evidence of ocular remnants. The present study reports the gross anatomical findings in a very rare case of unilateral and isolated anophthalmia of the right side. Despite the fact that the individual had only a rudimentary right optic nerve, an optic chiasm was developed and optic tracts were seen, but, interestingly, were asymmetric in the thickness, in such a manner that the right optic tract had increased thickness than the left optic tract. The details of the findings, with a brief review of anophthalmia and the mechanisms related to the morphogenesis of the chiasm and optic neural pathways are discussed. The exact embryogenesis of the pattern described in this case report is not clear, but this report will have implications in studies of axonal guidance and development of visual apparatus. A similar appearance has been reported in a follow up MRI study of early monocular enucleation in unilateral retinoblastoma cases, but the occurrence of asymmetric optic tracts in a case of unilateral anophthalmia is, to the best knowledge of the authors, a new finding in a very rare congenital anomaly.

Increased cortical surface area and gyrification following long-term survival from early monocular enucleation.

PurposeRetinoblastoma is typically diagnosed before 5 years of age and is often treated by enucleation (surgical removal) of the cancerous eye. Here, we sought to characterize morphological changes of the cortex following long-term survival from early monocular enucleation.MethodsNine adults with early right-eye enucleation (≤48 months of age) due to retinoblastoma were compared to 18 binocularly intact controls. Surface area, cortical thickness, and gyrification estimates were obtained from T1 weighted images and group differences were examined.ResultsEarly monocular enucleation was associated with increased surface area and/or gyrification in visual (i.e., V1, inferior temporal), auditory (i.e., supramarginal), and multisensory (i.e., superior temporal, inferior parietal, superior parietal) cortices compared with controls. Visual cortex increases were restricted to the right hemisphere contralateral to the remaining eye, consistent with previous subcortical data showing asymmetrical lateral geniculate nucleus volume following early monocular enucleation.ConclusionsAltered morphological development of visual, auditory, and multisensory regions occurs subsequent to long-time survival from early eye loss.

Early monocular enucleation selectively disrupts the development of neural mechanisms for face perception

Early monocular enucleation selectively disrupts the development of neural mechanisms for face perception

Altered anterior visual system development following early monocular enucleation

PurposeRetinoblastoma is a rare eye cancer that generally occurs before 5 years of age and often results in enucleation (surgical removal) of the cancerous eye. In the present study, we sought to determine the consequences of early monocular enucleation on the morphological development of the anterior visual pathway including the optic chiasm and lateral geniculate nucleus.MethodsA group of adults who had one eye enucleated early in life due to retinoblastoma was compared to binocularly intact controls. Although structural changes have previously been reported in late enucleation, we also collected data from one late enucleated participant to compare to our early enucleated participants. Measurements of the optic nerves, optic chiasm, optic tracts and lateral geniculate nuclei were evaluated from T1 weighted and proton density weighted images collected from each participant.ResultsThe early monocular enucleation group exhibited overall degeneration of the anterior visual system compared to controls. Surprisingly, however, optic tract diameter and geniculate volume decreases were less severe contralateral to the remaining eye. Consistent with previous research, the late enucleated participant showed no asymmetry and significantly larger volume decreases in both geniculate nuclei compared to controls.ConclusionsThe novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.

Impaired Face Processing in Early Monocular Deprivation from Enucleation

We investigated the effects of early monocular enucleation (ME) (surgical removal of one eye) on a high-level spatial visual ability, namely face perception. Early monocular deprivation of pattern vision from disorders such as strabismus, amblyopia, or cataract is associated with impairments in low-level spatial vision. This is inconsistent with studies of early ME that show either equivalent or enhanced low-level spatial vision compared with controls. Impairments on some aspects of face perception (i.e., feature-spacing and holistic face processing, both of which mature later in life) have been found with early pattern deprivation from congenital cataract. It is not clear whether the intact low-level spatial vision with ME will also persist with high-level face perception or whether deficits similar to those found with cataract will emerge. We tested individuals who have experienced early ME and controls on a series of high-level spatial visual tasks that measure feature-spacing, feature, and holistic face processing. The ME group were slower for feature spacing and feature tasks. Furthermore, the ME group did not exhibit the normal pattern of poorer performance on the aligned compared with misaligned composite face discrimination tasks, demonstrating a lack of the composite face effect. However, they did show the normal pattern of poorer performance on same vs. different trials on the aligned tasks. These results indicate an impairment in the feature spacing and feature aspects of face perception with ME. They also suggest a present yet, incomplete, development of holistic face processing in this group. Although the complete removal of inhibitory binocular interactions and/or the absence of binocular competition in early ME may result in cortical reorganization of the visual system and preserve low- to mid-level spatial vision, it may be insufficient for the maturation of high-level face perception.

Cortical thickening of early visual areas in early monocular enucleation

Cortical thickening of early visual areas in early monocular enucleation

Development and plasticity of the retina in the opossum Monodelphis domestica

We investigated the rate of cell proliferation and death in the retina of the Monodelphis opossum during its postnatal development and the influence of early monocular enucleation on these processes. Our results show that in the opossum, as in other marsupials, the peak of the retinal cells divisions occurs postnatally and that generation of retinal cells continues till the time of eye opening (P34), except of the marginal rim, where it continued till P60. Ganglion and amacrine cells are generated between postnatal days (P) P4 and P9, while bipolar cells and photoreceptors are generated simultaneously between P14 and P25. The peak of ganglion cell death as detected by the TUNEL method occurs around P14-19 in the center of retina. The second peak of apoptosis appears in the inner nuclear layer (INL) at P19-25. Gliogenesis takes place between P25 and P34. We also found that monocular enucleation performed during the early period of retinal development (P0-P7) did not influence proliferation, developmental apoptosis or other developmental processes in the retina of the remaining eye.

Reorganization of the uncrossed visual pathways as revealed by Fos-like immunoreactivity in rats with neonatal monocular enucleation

To elucidate the neuronal characteristics of the functional expansion in the uncrossed visual pathways (UXVPs), resulting from early monocular enucleation in rats, the feasibility of stimulus-dependent induction of the immediate early gene c-fos was examined immunohistochemically. In the UXVPs of rats with monocular enucleation at birth, patterned visual stimuli induced Fos-like immunoreactive (FLI) neurons much more densely in wide areas of the superficial layer throughout the superior colliculus (SC), and in the striate and extrastriate areas of the visual cortex (VC). In the UXVPs of rats monocularly enucleated after maturity, however, only a few stimulus-dependent FLI neurons were scattered in the restricted portions of the SC and the VC.

Contrast sensitivity in one-eyed subjects

The effects of early monocular form deprivation on the developing mammalian visual system, and the anatomical and physiological consequences of early monocular enucleation, suggest that the remaining eye of human subjects who had the other eye removed early during development might be capable of supernormal performance. To test this inference, the achromatic contrast sensitivity of the remaining eye of subjects who had the other eye removed at different ages after birth was compared with that of normal subjects tested under monocular and binocular conditions. The results show that all subjects who had an eye removed during early development had a higher contrast sensitivity than the better eye of control subjects. Furthermore, the earlier in development that the eye was removed, the lower the spatial frequency at which contrast sensitivity is enhanced compared with measurements made in the better eye of control subjects, and the larger the range of spatial frequencies over which contrast sensitivity is supernormal.

Neonatal monocular enucleation and the geniculo-cortical system in the golden hamster: shrinkage in dorsal lateral geniculate nucleus and area 17 and the effects on relay cell size and number.

We have examined the effects of neonatal monocular enucleation on the volume of the dorsal lateral geniculate nucleus (dLGN), the area of area 17, and the size and numbers of geniculate relay neurons identified by retrograde transport of HRP from cortex. Compared to values for normal animals, the only significant change contralateral to the remaining eye was an increase in relay cell radius. The effects ipsilateral to the remaining eye were more widespread: we found significant reductions in the volume of the dLGN (27% reduction), the area of striate cortex (22%), and the number (16%) and average soma radius (6%) of geniculate relay neurons. The relay neurons were also more densely packed, suggesting that other geniculate cell types were affected similarly, although this was not explicitly examined. These changes were not uniform throughout the nucleus, and as such, reflected the changes in retinal input. The greatest reduction in cell size occurred in the region of the ipsilateral dLGN receiving the most sparse retinal input subsequent to enucleation. Nor was the shrinkage of the dLGN uniform, being most apparent in the coronal plane especially along the axis orthogonal to the pia; there appeared to be little change in the anteroposterior extent. Shrinkage in area 17 ipsilateral to the remaining eye was the same (about 22%) whether it was defined by myelin staining or transneuronal transport of WGA-HRP. These results show that the transneuronal changes seen in the organization of visual cortex after early monocular enucleation in rodents are associated with only a moderate loss of geniculate relay cells.

Effect of a very early monocular enucleation upon the development of the uncrossed retinofugal pathway in ferrets

Monocular enucleations were done in ferret embryos before or during the earliest stages of development of the retinofugal pathway (E23-E26). The effects on the development of the uncrossed pathway from the surviving eye were assessed on embryonic day 30. This stage was chosen for two reasons: (1) we show that in normal development a substantial uncrossed component from the temporal crescent has developed by E30; and (2) the pathway cannot yet have been affected by the cell death that normally occurs in the retina in the perinatal period. Using DiI labelling from either the temporal crescent or the optic nerve head, we have shown that such early enucleations prevent the formation of the uncrossed pathway from the temporal crescent of the surviving eye. Enucleation at E23/24, before or during the period when the first axons reach the chiasm, prevents the formation of the uncrossed projection. The axons that would normally take an uncrossed course stall lateral to the midline of the optic chiasm. At E26, when many axons have reached the optic chiasm, but none yet come from the temporal crescent, enucleation causes a dramatic reduction in the uncrossed projection, and the complete abolition of the normal uncrossed pathway from the temporal crescent. This demonstrates that there is a requirement for an interaction between the axons of the two eyes at the optic chiasm to establish the normal formation of the uncrossed pathway at the optic chiasm.

Regulation of retinal ganglion cell axon arbor size by target availability: mechanisms of compression and expansion of the retinotectal projection.

The ability of pre- and postsynaptic populations to achieve the proper convergence ratios during development is especially critical in topographically mapped systems such as the retinotectal system. The ratio of retinal ganglion cells to their target cells in the optic tectum can be altered experimentally either by early partial tectal ablation, which results in an orderly compression of near-normal numbers of retinal projections into a smaller tectal area, or by early monocular enucleation, which results in the expansion of a reduced number of axons in a near-normal tectal volume. Our previous studies showed that changes in cell death and synaptic density consequent to these manipulations can account for only a minor component of this compensation for the population mismatch. In this study, we examine other mechanisms of population matching in the hamster retinotectal system. We used an in vitro horseradish peroxidase labeling method to trace individual retinal ganglion cell axons in superior colliculi partially ablated on the day of birth, as well as in colliculi contralateral to a monocular enucleation. We found that individual axon arbors within the partially lesioned tectum occupy a smaller area, with fewer branches and fewer terminal boutons, but preserve a normal bouton density. In contrast, ipsilaterally projecting axon arbors in monocularly enucleated animals occupy a greater area than in the normal condition, with a much larger arbor length and greater number of boutons and branches compared with normal ipsilaterally projecting cells. Alteration of axonal arborization of retinal ganglion cells is the main factor responsible for matching the retinal and tectal cell populations within the tectum. This process conserves normal electrophysiological function over a wide range of convergence ratios and may occur through strict selectivity of tectal cells for their normal number of inputs.

Prenatal disruption of binocular interactions creates novel lamination in the cat's lateral geniculate nucleus.

The elimination of retinogeniculate afferents from one eye on embryonic day 44 (E44) has pronounced effects on the formation of the cellular laminae in the cat lateral geniculate nucleus (LGN). Only two laminae form: a dorsal, "magnocellular" layer, and a ventral, "parvocellular" layer. Soma size measurements and previously reported patterns of termination of retinogeniculate axons suggest that the dorsal lamina is a coalescence of the normal A-laminae and the dorsal, magnocellular division of layer C, while the ventral layer is a composite of the parvocellular sublamina of layer C and the remaining C-laminae. This is a novel pattern of lamination in the LGN that differs from that found in the normal nucleus, not only in that there are now only two cell layers rather than the normal five, but also in that the interlaminar zone occurs in an abnormal location. This result is markedly different from that observed in other species where interlaminar zones present after early monocular enucleation are a subset of the ones which would normally be present. We suggest that, in the absence of ongoing binocular interactions, interactions between functionally distinct retinal ganglion cell classes from the remaining eye may direct the formation of cell laminae in the LGN, even when such interactions are not normally operative.