The possibility of artificial tissue or organ for the eye.
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Studies of the plasticity of retinal projections following neonatal eye ablations in rats and hamsters have demonstrated an enhanced ipsilateral projection which affects both the terminal fields and the number of ipsilaterally projecting cells. The enhancement has been attributed to an excess of bilateral branching by single optic nerve axons, but this claim was not supported by the present study. Double retrograde labels were used to quantify the ipsilateral enhancement and measure the extent of bilateral branching in hamsters with neonatal eye removals. In 19 normal Syrian golden hamster retinas the average number of bilaterally projecting retinal ganglion cells (BPRGCs) was 7.4 (SD = 3), and the average number of ipsilaterally projecting retinal ganglion cells (IPRGCs) was 1349 (SD = 478) (Hsiao, K., G. M. Sachs, and G. E. Schneider (1984) J. Neurosci. 4: 359-367). In nine retinas of hamsters with removal of one eye at birth, the average number of BPRGCs was 25.3 (SD = 9.2), and the average number of IPRGCs per retina was 2036 (SD = 414). Although the increase in BPRGCs is statistically significant, it accounted for only 2 to 3% of the 51% increase in the number of IPRGCs. Various possible mechanisms underlying the formation of the enhanced projection are enumerated, and it is concluded that the predominant mechanism is a reduction of cell death in the developing population of IPRGCs. The responses of IPRGCs and BPRGCs to early eye enucleations were also examined with respect to age at enucleation and cell size. No difference in size was found between IPRGCs and BPRGCs in monocular hamsters compared to normal hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)
We have examined whether the superficial layers of the superior colliculus (SC) provide the source of visual signals that guide the development of the auditory space map in the deeper layers. Anatomical tracing experiments with fluorescent microspheres revealed that a retinotopic map is present in the newborn ferret SC. Aspiration of the caudal region of the superficial layers of the right SC on postnatal day 0 did not cause a reorganization of this projection. Consequently, recordings made when the animals were mature showed that visual units in the remaining superficial layers in rostral SC had receptive fields that spanned a restricted region of anterior space. Auditory units recorded beneath the remaining superficial layers were tuned to corresponding anterior locations. Both the superficial layer visual map and the deeper layer auditory map were normal in the left, unoperated SC. The majority of auditory units recorded throughout the deeper layers ventral to the superficial layer lesion were also tuned to single sound directions. In this region of the SC, however, we observed much greater scatter in the distribution of preferred sound directions and a significant increase in the proportion of units with spatially ambiguous responses. The auditory representation was degraded, although many of these units were also visually responsive. Equivalent lesions of the superficial layers made in adult ferrets did not alter the topographic order in the auditory representation, suggesting that visual activity in these layers may be involved in aligning the different sensory maps in the developing SC.
The number and distribution of cells in the retinal ganglion layer have been examined in Nissl-stained wholemounts during postmetamorphic life in Xenopus laevis. Total cell number at metamorphic climax, in the 3 and 4 month juveniles and in 5 year adults were 30,000-41,000, 45,000-51,000 and 71,000-82,000 respectively. Optic axon counts of 29,000, 39,000 and 58,000 at these stages suggested that most cells counted were ganglion cells and that their number doubled during this period. Cell distribution changed after metamorphosis producing nasal and temporal regions of higher density in juveniles and adults. These results are discussed in relation to retinal growth and plasticity of retinotectal connections.
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The circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals, exhibits astroglial plasticity indicated by GFAP expression over the 24-h period. In this study, we evaluated the role of neuronal retinal input in the observed changes. Modifications of retinal input, either by rearing animals under darkness (DD) or under constant light (LL), or by suppressing afferent input (bilateral enucleation), induced drastic changes in astroglial plasticity. In enucleated animals, a dramatic decrease in GFAP expression was evident in the area of the SCN deprived of retinal projections, whereas persistence of a rhythmic variation was in those areas still exhibiting GFAP expression. By contrast, no changes in astrocytic plasticity were detected in hamsters maintained under LL. These data suggest two fundamental roles for astrocytes within the SCN: (1) to regulate and mediate glutamate released by retinal terminals throughout the neuronal network to facilitate photic signal transmission; (2) to contribute to synchronization between suprachiasmatic neurons.
Lesions in cats, rats, and monkeys that spare more than 2% of the optic tract or visual cortex cause trivial deficits on most measures of vision. Overlap in the topography of the visual system may allow the spared remnant to 'see' a wider field of vision than the physiological map predicts. We tested whether monkeys left with only the lower retinal-field portion of their striate map could see with information coming from the upper half of the retina. In 6 rhesus monkeys the ganglion fibers exiting from the lower half of both retinae were cut with a photocoagulator. Later, the portion of area 17 which, according to the electrophysiological map, controls upper retinal vision, was ablated bilaterally. The combined retinal and striate lesions overlapped to include the entire visual field. Together they produced cortical blindness. The monkeys' performance of two pattern and object tasks remained at chance throughout the survival period. A previous study has described considerable sparing of vision after combined optic tract and visual cortex lesions in cats. Differences in the lesion methods and in the anatomy of the cat and monkey visual system may explain the disagreement.
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Electrophysiological recording in primary visual cortex (VI) was performed both prior to and in the hours immediately following the creation of a discrete retinal lesion in one eye with an argon laser. Lesion projection zones (LPZs; 21-64 mm2) were defined in the visual cortex by mapping the extent of the lesion onto the topographic representation in cortex. There was no effect on neuronal responses to the unlesioned eye or on its topographic representation. However, within hours of producing the retinal lesion, receptive fields obtained from stimulation of the lesioned eye were displaced onto areas surrounding the scotoma and were enlarged compared with the corresponding field obtained through the normal eye. The proportion of such responsive recording sites increased during the experiment such that 8-11 hours post-lesion, 56% of recording sites displayed neurons responsive to the lesioned eye. This is an equivalent proportion to that previously reported with long-term recovery (three weeks to three months). Responsive neurons were evident as far as 2.5 mm inside the border of the LPZ. The reorganization of the lesioned eye representation produced binocular disparities as great as 15 degrees, suggesting interactions between sites in VI up to 5.5 mm apart.
Elevation of body temperature by 2-3 degrees C induces a 2.7 kilobase hsp70 mRNA species in the rabbit retina within 1 hr. In situ hybridization with thin sections derived from plastic-embedded tissue permitted a higher level of resolution of retinal cell types compared to procedures which involved the use of frozen tissue sections. A prominent induction of hsp70 mRNA in retinal ganglion cells was observed when an hsp70 riboprobe was utilized for in situ hybridization. These results indicate that this neuronal cell type responds rapidly to fever-like body temperatures by inducing one of the major heat shock genes.
The uncrossed retinotectal projection restricts its terminal fields to the ventral boundary of the visual layers at the rostral tectum during early post natal development. During this critical period, temporal retinal lesions in one eye induce laminar rearrangements in the uncrossed pathway of the intact eye toward the collicular surface previously occupied, almost exclusively, by the crossed retinal axon population. We have compared, using anterograde tracing techniques, the time course and magnitude of the axonal sprouting resulting from retinal lesions in neonates and adults. Early retinal lesions (within the first two post natal weeks) induced extensive and rapid plasticity of the ipsilateral projection 48 h after the lesions. On the third post natal week, similar retinal lesions induced a small reorganization of the intact eye's uncrossed projection within a 3-week survival time. Nevertheless, giving the animals a long-term survival, resulted in an increased plastic capability, suggesting that even after the critical period, intact retinal axons can respond efficiently to injury. The results suggest two phases of axonal reorganization within this subcortical pathway: a rapid plasticity within the critical period and a slow, but continuous plasticity in adulthood.
The uncrossed retinotectal projection of rats undergoes extensive axonal elimination and subsequent growth of axonal arbors in topographically appropriate territories within the first two/three postnatal weeks. Nitric oxide has been implicated in development and stabilization of synapses in the retinotectal pathway since blockade of nitric oxide synthesis disrupts the normal pattern of retinal innervation in subcortical nuclei. The present work investigated the role of arachidonic acid pathway in the development and maintenance of ipsilateral retinotectal axons. We also investigated the role of this retrograde messenger in the modulation of plasticity that follows retinal lesions in the opposite eye. Pigmented rats received systemic treatment with quinacrine, a phospholipase A2 inhibitor, indomethacin, a cyclooxygenase inhibitor, nordihydroguaiaretic acid, a 5-lipoxygenase inhibitor or vehicle during 4-8 days at various postnatal ages. Rats given a unilateral temporal retinal lesion were treated with either quinacrine or vehicle during the same period. For anterograde tracing of ipsilateral retinal projections, animals received intraocular injections of horseradish peroxidase. Before the third postnatal week no difference was observed in the laminar or topographic organization of the ipsilateral retinotectal projection between vehicle and treated rats in either normal or lesion conditions. After the third postnatal week, however, systemic blockade of phospholipase A2 or 5-lipoxygenase, but not cyclooxygenase induced sprouting of uncrossed axons throughout the collicular visual layers in unoperated rats. In retinal lesion groups, phospholipase A2 blockade increased the sprouting of uncrossed intact axons to the collicular surface in the same period. The results suggest that arachidonic acid or lipoxygenase metabolites play a role in the maintenance of the retinotectal synapses after the critical period and that the blockade of the arachidonic acid pathway induces reactive sprouting of retinal axons late in development.
During development, retinal ganglion cells undergo conspicuous structural remodeling as they gradually attain their mature morphology and connectivity. Alterations in their dendritic organization and in their axonal projections can also be achieved following early insult to their targets or their afferents. Other retinal cell types are thought not to display this same degree of developmental plasticity. The present review will consider the evidence, drawn largely from recent experimental studies in the carnivore retina, that photoreceptors also undergo structural remodeling, extending their terminals transiently into inner plexiform layer before retracting to the outer plexiform layer. The determinants of this transient targeting to the inner plexiform layer are considered, and the role of cholinergic amacrine cells is discussed. The factors triggering this retraction are also considered, including the concurrent maturational changes in outer segment formation and in the differentiation of the outer plexiform layer. These results provide new insight into the life history of the photoreceptor cell and its connectivity, and suggest a transient role for the photoreceptors in the circuitry of the inner retina during early development, prior to the onset of phototransduction.
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We have examined the following aspects of retinal development in the frog, Rana pipiens: (1) the overall pattern of cell addition to the retina; (2) the relative rate of retinal ganglion cell (RGC) accretion; and (3) the changes in RGC density during larval development. In addition, we have studied the development of the retinal projection onto the tectum by means of the anterograde transport of horseradish peroxidase (HRP) and measurements of the volume of tectal neuropil at several larval stages and in postmetamorphic frogs. We find that the addition of new cells to the retina of Rana pipiens larva is restricted to the ciliary margin and that this addition is concentric at all larval stages. Additionally, the morphometric measures of retinal and tectal growth, along with the HRP histochemistry, indicate that the retinal projection exhibits considerable plasticity during normal development. The plasticity we observe in normal development may explain why the retinotectal projection can compensate its area and volume in experimental paradigms that effect drastic changes in innervation density.
Plastic corrosion casts of the rat retinal vasculature were studied by scanning electron microscopy. This technique demonstrated the entire retinal vasculature of the rat. The retinal blood vessels supplying the rat's retina have a definite and fairly constant pattern. At the disk there are usually six main artery and vein branches that run symmetrically towards the periphery. Veins are wider and more tortuous. The characteristic arrangement of endothelial cell nuclear indentations clearly differentiates arteries from veins. Retinal arteries have side-arm and dichotomous branchings. The number of vessel branches is greater on the nasal side than on the temporal side of the retina. The vein-over-artery crossing phenomenon is more frequent than the artery-over-vein. Retinal capillaries appear tortuous and are arranged cylindrically in two layers. The superficial network of capillaries comes essentially from arterioles, while deep layer capillary networks are more regularly and densely arranged and are mainly connected with venules. The inner and the outer capillary networks have interconnections, vertical runs and short vascular bridges. Within the retina there are regional variations in capillary pattern and distribution. More regular, dense and rich capillary networks are observed in the peripheral area than at the posterior pole area. No arteriovenous shunts were seen. The study of such plastic casts makes possible a more accurate assessment of some aspects of vascular abnormalities. These findings will be helpful in further investigations of retinal vascular abnormalities.
Horizontal cell dendrites protruding into the cone pedicles in fish retina exhibit a light-dependent plasticity. In a light-adapted retina they form numerous spinules having membrane densities at their tips. These spinules disappear during dark adaptation. Experiments with light- or dark-adapted retinas which were incubated in glutamate or its agonists and antagonists, respectively, revealed that this putative cone transmitter is able to reduce the expression of spinules in a light-adapted retina. Dopamine, on the other hand, induces the formation of spinules in a dark-adapted retina and haloperidol reduces the expression in a light-adapted retina. These data suggest a control of spinules plasticity through two retinal neurotransmitter systems.