Abnormal pigmentation and unusual morphogenesis of the optic stalk may be correlated with retinal axon misguidance in embryonic Siamese cats

Studies of albino rodents have shown that an absence of pigment in the developing optic stalk may alter the position of the first retinal fibers that grow toward the brain, thereby disrupting the gross topographic relationship of fibers in the nerve (Silver and Sapiro: J. Comp. Neurol. 202:521-538, '81). The abnormalities associated with albinism are more extensive in the Siamese cat than-in previously studied species. Therefore, any abnormalities in differentiation of the stalk and axon guidance may be more readily detected. To investigate the guidance and/or misguidance of optic axons, light and electron microscope analyses were made of serial sections through the optic stalk in normally pigmented and Siamese fetal cats. On E20, before axons enter the optic stalk, the only clear morphological distinction between Siamese and normal cats is the distribution of pigment in the stalk. Pigment is found in the dorsal stalk cells of the normal cat for 200 microns from the optic disc. Although the retinal pigment epithelium of the Siamese optic stalk. By E23 axons invade the ventral optic stalk in both strains. Concurrent with the early stages of axonal exit from the retina, there is complete separation of the stalk's dorsal and ventral tiers. As the cleavage occurs, basal lamina invaginates into the zone of separation following along the plane of the old lumen. The ventral stalk fills with axons while the dorsal tier is shed gradually. In contrast, in the Siamese cat, dorsal stalk cells are not sloughed off properly and instead are incorporated ectopically into the nerve. Basal lamina invagination is irregular. Axons do not fill the Siamese stalk symmetrically but enter the region of ectopic cells, which in turn disrupts gross fiber position. Usually, in the mutant, axons originating from the retina temporal to the optic fissure are those that invade the dorsal tier of ectopic cells. The altered position of optic axons in the mutant stalk may provide an explanation for the chiasmatic misrouting of optic axons in this species.     

The early development of the optic nerve and chiasm in embryonic rat

To establish the time course and major features of the development of the optic nerve and chiasm in the embryonic rat, the growth of axons from the retina to the brain has been studied by light and electron microscopy. On embryonic day 14 (E14), the first axons are generated by retinal ganglion cells. Fascicles of axons can be detected in the optic stalk at E14.5 and in the diencephalon by E15.0. In the vitreal retina and optic fissure, large extracellular spaces resemble the oriented channels previously described in the mouse. They form approximately 12 hours before the invasion of optic axons and contain hyaluronic acid. In the optic stalk and diencephalon of the rat, similar spaces are not present, but the timed autolysis of neuroepithelial cells could provide a pathway of minimal resistance for the earliest axons. Degenerating cells are prominent in the ventral stalk and rostral diencephalon prior to the arrival of the first optic axons that preferentially invade these regions. The role of pigment in the development of visual pathways is controversial. In one strain of rat, Manchester Hooded, the retinae are heavily pigmented, but little pigment is seen at any stage in the stalk; in albinos, pigment is absent from both retina and stalk. However, the distribution of axons within the developing optic stalk is very similar in both strains, suggesting that the reduction in size of the ipsilateral pathway observed in the albino rat compared with the Manchester Hooded is not due to a lack of pigment in the optic stalk early in development. Several factors previously reported to contribute to the development of retinotopic order in other species are also present in the rat. These include the sequence in which axons grow into the stalk, and fasciculation. Intermembranous contacts observed between growth cones and adjacent tissues suggest one mechanism by which fasciculation occurs. A small group of fascicles, which may represent the ipsilateral projection, diverges from the crossing fibers on E15.5, without evidence of being deflected by any glial or other structures.     

Differential action of the albino mutation on two components of the rat's uncrossed retinofugal pathway

The development of the uncrossed retinofugal pathways in normally pigmented and albinorats, aged from embryonic day (E) 14.5 to E18.5, was investigated. Dil was placed into one optic tract and the retinal origin of the uncrossed component, as well as its course in the optic stalk, was studied. The results show that, as in the mouse, the uncrossed retinal projection has two components. The first component is seen at E15.5 in normally pigmented animals. It develops exclusively in the central parts of the retina and is normal in albino littermates. The second component, which arises from the peripheral parts of the ventrotemporal retina, is seen two days later at E17.5 in all animals but is significantly smaller in albinos than in their pigmented littermates. Studies of axons in the optic stalk labelled retrogradely with DiI placed in the optic tract indicate that the uncrossed axons have no preference for any position in the stalk except when they approach the chiasm, where they tend to accumulate at the caudal region of the stalk. The uncrossed axons intermingle with the crossed axons along the entire length of the stalk. In albino embryos, no obvious difference in the prechiasmatic course of uncrossed axons was seen at any age examined. It is concluded that the albino mutation in rats affects the late ventrotemporal component of the uncrossed pathway selectively. It does not act on the early central component. Further, the intermingling of crossed and uncrossed axons in the stalk and the apparently unaffected prechiasmatic course of uncrossed axons in albinos indicate that the albino gene has its primary action in the retina. © 1993 Wiley-Liss, Inc.     

Changes in fiber order in the optic nerve and tract of rat embryos

In order to define the extent to which retinotopic order in the optic pathways may contribute to fiber segregation at the chiasm or to the formation of central maps, the arrangement of fibers in the optic nerve and tract of rat embryos, on embryonic days 16.5 and 18.5, has been studied by placing a small granule of Dil in one of the four quadrants of the retina and tracing the filled fibers through transverse sections of the retinofugal pathway with confocal microscopy. There is a distinct quadrant-specific order in the optic stalk immediately behind the eye, with fibers from the ventral nasal, dorsal nasal, dorsal temporal, and ventral temporal retina arranged sequentially across the rostrocaudal axis of the cross section of the stalk. However, this distinct order is not maintained very far. There is a gradual increase in the degree of overlap between fibers from the different quadrants as the fibers pass towards the chiasm. The dorsal groups of fibers intermingle extensively along almost the entire length of the stalk, but the fibers from ventral sectors remain separate until they reach the prechiasmatic region, where the ventral temporal and the ventral nasal fibers spread the throughout the rostrocaudal extent of the stalk and the chiasm. The initial quadrant-specific order is completely lost at the chiasm. However, beyond the optic chiasm, the fibers are reorganized into another distinct order. In the optic tract, there is a segregation of dorsal from ventral fibers, but the nasal and temporal groups remain intermingled. The results of this study indicate that the earliest fibers in the developing optic tract are arranged according to topographical rules that differ from those obtaining behind the eye. Since all topographical order is lost between these two levels, there must be an active storing mechanism in the region where the chiasm joins the tract. Possibly this mechanism is related to the development of the dorsoventral axis of the topographic maps in the central visual targets. © 1994 Wiley-Liss, Inc.     

The retina and central projections of heterochromic rats.

The eyes and central projections of heterochromic rats, which have one pigmented (ruby) and one nonpigmented (red) eye, were studied. Both eyes in fact have no clear indication of pigment in the pigment epithelium, although in the ruby eye, pigment is present in the choroid and iris. The central projection from each eye is albino-like in the representation of the uncrossed optic pathway to the lateral geniculate body, which is best demon-strated using the autoradiographic pathway tracing technique. This suggests therefore that factors relating to the pigmentation of the pigment epithelium rather than the rest of the eye are important in producing the albino aberration.     

Retinogeniculate projections in the rabbits of the albino allelomorphic series

Retinogeniculate pathways have been studied by fiber degeneration and autoradiographic methods in rabbits that are homozygous for alleles of the albino series of genes. It has been found that albino and Himalayan rabbits, which both lack all melanin pigment in the eye, have a similar abnormality of the retinogeniculate pathway. The number of ipsilateral optic fibers going to the lateral geniculate nucleus is reduced in these rabbits, the ipsilateral projection forms a discontinuous terminal zone instead of the normal continuous zone, and some of the ipsilateral axons terminate in an inappropriate part of the nucleus, so that regions receiving a crossed input in normal rabbits receive an uncrossed input in the abnormal rabbits. Chinchilla rabbits show a slightly reduced fur pigmentation but have a normal distribution of pigment in the retinal pigment epithelium and these rabbits have normal retinogeniculate pathways. In addition, the normal retinogeniculate pathway was studied. Autoradiographic methods show that the β segment of the lateral geniculate nucleus receives a contralateral input. Hence, earlier views that this segment projects to the visual cortex but receives no retinal input, are untenable. Further, in the autoradiographic material it was not possible to identify separate ipsilateral laminae and it was concluded that in the normally pigmented rabbit the ipsilateral retinogeniculate projection forms one relatively continuous group.     

A mechanism for the guidance and topographic patterning of retinal ganglion cell axons

Three dimensional reconstruction, with the use of serial, 1-μm sections, has revealed a system of oriented intercellular spaces within the undifferentiated optic cup. These large openings appear in the marginal zone of the primitive retina and optic stalk prior to the formation of the first retinal ganglion cell axons. The spaces at the region of the optic disc form sets of long, interconnecting tunnels oriented in the direction of the stalk. The spaces at the back and rim of the cup form blind, radially arranged pockets. The extracellular tunnels of the optic disc region strictly maintain their positions in relation to the optic fissure and, thus, discrete portions of the retina become connected by continuous openings with equivalent regions in the stalk. The path taken by the earliest outgrowing optic fibers is identical to the one previously established by the intercellular tunnels. We propose that the tunnel and pocket layout may provide directional and topographic information to the first forming optic axons.     

Visual system degeneration in the glaucomatous albino quail

The peripheral (eye, retina, optic nerve) and central (primary optic tracti and centers, centrifugal visual tractus and nucleus) visual system of an imperfect albino quail mutant with a sex linked recessive gene was examined in 32 specimens ages 1 week - 16 months-hatch using various histological techniques. During the first weeks the visual system was normal and comparable in its overall organization to that found in the pigmented quail. However, the ipsilateral retinal projections were observed to be weaker in the young mutant, then completely disappeared two months after birth. Initial signs of the bupthalmos, a form of spontaneous glaucoma, appeared between the 3rd and 5th months. This was characterized by a distention of the eye linked to an increase in intraocular pressure. The pathological process was progressive and at 16 months the eye was very prominent, the anterior chamber deep and a large and globular cornea was noted. The glaucoma progressively induced different histopathological changes in the visual system including: cupping of the optic disc, degeneration of optic axons and their parent ganglion and centrifugal cells and cavernous degeneration. All of these phenomena were identifiable at about the 10th post-natal month and progressed in a relatively constant and orderly manner. The retinal projections to the nucleus ectomamillaris, ventral and lateral optic tectum and ventral pretectum were the first to degenerate. The degeneration of optic fibers attaining the dorsal pretectum and dorsal thalamus occurred later. Furthermore the retrograde degeneration in the centrifugal isthmo-optic nucleus progressed from the external to the internal pole. The mechanisms involved in the selective degeneration of centrifugal and centripetal optic fibers is discussed.     

Factors guiding optic fibers in developing Xenopus retina

We have characterized, by electron microscopy, the growth of pioneering axons from the retina into the visual pathway during early development of Xenopus laevis. The subsequent development of following fibers from the growing retinal margin as they accumulated in the ganglion cell fiber layer (GCFL) of the retina was also studied. Extracellular channels bordered by neuroepithelial cells appear in the developing retina in a dorsal to ventral gradient before any pioneering axons are seen. Pioneering axons are subsequently observed in these channels, usually surrounded by neuroepithelial cell processes. Ruthenium red treatment of embryonic retinas reveals extracellular matrix (ECM) within these retinal channels, while extracellular spaces in the proximal optic stalk, just beyond the optic disc, lack this material. ECM is also seen in optic tectum wherever ingrowing retinal and nonretinal axons are found. The channels and the ECM contained within them may provide guidance cues for pioneering retinal axons. The early association of pioneering retinal axons with neuroepithelial cell processes (putative glia) appears to be important in further development of the GCFL. The so-called following fibers of ganglion cells, arising later in development, fasciculate with pioneer axons in extracellular spaces and form fiber bundles of the GCFL on top of the layer of glial cell endfeet. It is not clear whether pioneering axons, glial cell surfaces, or both serve as guidance cues for following fiber migration.     

Distribution and trajectory of uncrossed axons in the optic nerves of pigmented and albino rats

Ipsilaterally projecting axons in the optic nerve of the pigmented rat are limited to a roughly retinotopic location within the intraorbital segment of the nerve. However, immediately rostral to the chiasm they are widely dispersed. Here, the way in which this change in distribution arises is analysed by tracing individual fibers retrogradely labelled from the optic tract with horseradish peroxidase (HRP). A comparison is made between albino and pigmented animals. It is demonstrated that the change in this distribution occurs as a consequence of two types of shift in axon trajectory in the intracranial segment. Many axons change their location in the nerve gradually throughout this segment. However, in the proximal half of this region a number of axons also make abrupt changes in their trajectory by travelling at right angles across segments of the mediolateral axis of the nerve. These were seen in both the pigmented and albino animals. Although the albino has an abnormally small ipsilateral retinofugal pathway, the distribution of ipsilateral axons in the optic nerve is very similar to that seen in pigmented animals. Consequently, it is unlikely that position in the prechiasmatic nerve is related to the chiasmatic choice made by axons in this population.     

Retinal pigment epithelial integrity is compromised in the developing albino mouse retina

In the developing murine eye, melanin synthesis in the retinal pigment epithelium (RPE) coincides with neurogenesis of retinal ganglion cells (RGCs). Disruption of pigmentation in the albino RPE is associated with delayed neurogenesis in the ventrotemporal retina, the source of ipsilateral RGCs, and a reduced ipsilateral RGC projection. To begin to unravel how melanogenesis and the RPE regulate RGC neurogenesis and cell subpopulation specification, we compared the features of albino and pigmented mouse RPE cells during the period of RGC neurogenesis (embryonic day, E, 12.5 to 18.5) when the RPE is closely apposed to developing RGC precursors. At E12.5 and E15.5, although albino and pigmented RPE cells express RPE markers Otx2 and Mitf similarly, albino RPE cells are irregularly shaped and have fewer melanosomes compared with pigmented RPE cells. The adherens junction protein P‐cadherin appears loosely distributed within the albino RPE cells rather than tightly localized on the cell membrane, as in pigmented RPE. Connexin 43 (gap junction protein) is expressed in pigmented and albino RPE cells at E13.5 but at E15.5 albino RPE cells have fewer small connexin 43 puncta, and a larger fraction of phosphorylated connexin 43 at serine 368. These results suggest that the lack of pigment in the RPE results in impaired RPE cell integrity and communication via gap junctions between RPE and neural retina during RGC neurogenesis. Our findings should pave the way for further investigation of the role of RPE in regulating RGC development toward achieving proper RGC axon decussation. J. Comp. Neurol. 524:3696–3716, 2016. © 2016 Wiley Periodicals, Inc.     

Evaluation of the influence of optic stalk melanin on the chiasmatic pathways in the developing rodent visual system.

In a number of mammalian species, fibre outgrowth in the developing retinofugal pathway is coincident with the presence of melanin in the retinal part of the optic stalk. The presence of melanin is transient in this developing system and has been proposed to play a role in the guidance of retinofugal fibres. Further, it has been suggested that this stalk melanin accounts for the differences between the size of the uncrossed retinal component in pigmented and nonpigmented strains. However, a recent study showed that there is no melanin in the optic stalk of Manchester rats during fibre outgrowth. Since such rats supposedly have a normal pigment distribution and a normal pattern of decussation at the optic chiasm, this finding appears to undermine the suggested role played by stalk melanin in establishing the laterality of retinal fibre projections in other mammalian species. The aim of this study was to re-evaluate the relationship between melanin in the stalk and the development of the retinofugal pathway in three strains of rat: the Wild type, Long Evans Hooded, and the Albino. The Albino rat, which lacks melanin-bearing cells entirely, was shown to have the smallest uncrossed projection, approximately 1,340 ipsilaterally projecting cells (ipc), whereas the Long Evans (2,760 ipc) and the Wild-type strain (2425 ipc) were found to have a larger uncrossed retinal component. In both pigmented strains, melanin was restricted to the eye cup and absent from the optic stalk throughout all stages of development.(ABSTRACT TRUNCATED AT 250 WORDS)     

Visual system of the channel catfish (Ictalurus punctatus): III. Fiber order in the optic nerve and optic tract

In channel catfish the ganglion cell axons leave the retina via a ring of approximately 13 separate optic papillae. Each papilla serves an area of retina extending from the central zone of the retina to the periphery. Papillae located at a dorsal position in the ring serve exclusively dorsal retina. Ventrally located papillae, however, have an exaggerated peripheral retinal representation, so that they serve mostly ventral retina but also some areas of peripheral retina dorsal to the nasal and temporal poles. The ganglion cell axon bundles departing from the retina via individual papillae were labelled with horseradish peroxidase, and sections of the optic pathway were examined to reveal the topographic organization of the fibers. The topographic order of the optic nerve was dissimilar to that of cichlids and goldfish. Fibers from individual papillae remained together throughout the optic nerve. Close to the optic nerve head, the papillae were arranged as a continuum around the U-shaped optic nerve, without the discontinuity in the representation of the ventral retina seen in other fish. Fibers associated with the dorsal papillae were located at the tip of the caudolateral arm of the U, and fibers from ventral papillae were on the rostromedial arm. Fibers from nasally and temporally located papillae were found on the base of the U. By the level of the optic chiasm the U shape had flattened out but retained the relative ordering of the papillae. Rotation of the nerve as it became the optic tract brought the representation of the ventral papillae to the dorsal pole of the tract, and the dorsal papillae to the ventral tract. It was only in the optic tract that rearrangement of fibers became apparent. As described above, the axons of some ganglion cells in dorsal, peripheral retina left the retina and travelled through the optic nerve with axons from extreme ventral retina. In the optic tract, these dorsal fibers joined the main body of fibers from the dorsal retina. The significance of these observations for theories of fiber rearrangement is discussed.     

Relationship of ocular pigmentation to the boundaries of dorsal and ventral retina in a nonmammalian vertebrate

The goldfish eye and retina are partitioned traditionally into dorsal and ventral sectors by a horizontal meridian that passes through the optic disc and is perpendicular to a vertical meridian that extends from the remnant of the choroid fissure through the optic disc. Axons of retinal ganglion cells (RGCs) situated above the horizontal meridian are thought to reach the optic tectum via the ventrolateral optic tract and axons of RGCs situated below the horizontal meridian are thought to reach the optic tectum via the dorsomedial optic tract. When cobaltous-lysine was applied to small temporal retinal slits that were centered on the traditional horizontal meridian, filled fibers were found in the dorsomedial, but not in the ventrolateral, optic tract (Springer and Mednick, '83). Since cobalt-filled axons should have been found in both optic tracts, the traditional horizontal meridian does not indicate the actual boundary between dorsal and ventral retina. We report here that the goldfish iris contains nasal and temporal pigmentation lines (darts) that are each located approximately 21 degrees above the traditional horizontal retinal meridian. Cobalt applied to retinal slits located just above the darts filled RGC axons in the ventrolateral optic tract and cobalt applied to retinal slits just below the darts filled RGC axons in the dorsomedial optic tract. Converging evidence for the reliability of the darts as indicators of the boundary between dorsal and ventral retina was obtained by applying cobalt to severed RGC axons along the dorsomedial edge of the tectum. Cobalt-filled RGCs were found below the nasal dart.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic control of retinal ganglion cell projections.

We have assessed the effects of 15 pigmentation mutations on the development of retinal ganglion cell projections in mice in two ways: (1) by analyzing the pattern of innervation of the ipsilateral lateral geniculate nucleus as mapped in autoradiograms of brains of animals killed 12 days after intravitreal injection of 3H-proline into one eye and (2) by determining the ratio of axonally transported radioactive protein in the contralateral and ipsilateral optic tracts after similar intravitreal injections. Analysis of the ratio of transported protein in the two optic tracts provides a new and useful assay of the degree of decussation in experimental animals. The effects of the mutations on eye pigmentation, whole eye melanin content and relative tyrosinase activity also were examined. The degree of ipsilateral innervation generally correlates with the degree of pigmentation of the retinal pigment epithelium and with tyrosinase activity. However, discrepancies have been found in ch and ce mutants. In these animals the pigment epithelium is well pigmented, and the area of ipsilateral innervation in the lateral geniculate nucleus is extensive, despite a high ratio of label in contralateral to ipsilateral optic tracts and low tyrosinase activity. Furthermore, mice heterozygous for the c2J allele have pigmentation and optic projections that are normal even though tyrosinase is reduced to 40% of normal. The few anomalous results suggest that alternative or additional factors may control optic axon projections.     

Early development of the optic nerve in the turtle Mauremys leprosa

We show the distribution of the neural and non-neural elements in the early development of the optic nerve in the freshwater turtle, Mauremys leprosa, using light and electron microscopy. The first optic axons invaded the ventral periphery of the optic stalk in close relationship to the radial neuroepithelial processes. Growth cones were thus exclusively located in the ventral margin. As development progressed, growth cones were present in ventral and dorsal regions, including the dorsal periphery, where they intermingled with mature axons. However, growth cones predominated in the ventral part and axonal profiles dorsally, reflecting a dorsal to ventral gradient of maturation. The size and morphology of growth cones depended on the developmental stage and the region of the optic nerve. At early stages, most growth cones were of irregular shape, showing abundant lamellipodia. At the following stages, they tended to be larger and more complex in the ventral third than in intermediate and dorsal portions, suggesting a differential behavior of the growth cones along the ventro-dorsal axis. The arrival of optic axons at the optic stalk involved the progressive transformation of neuroepithelial cells into glial cells. Simultaneously with the fiber invasion, an important number of cells died by apoptosis in the dorsal wall of the optic nerve. These findings are discussed in relation to the results described in the developing optic nerve of other vertebrates.     

Changes in the numbers of retinal ganglion cells and optic nerve axons in the developing albino rabbit

In albino rabbits aged from the 16th postconceptional day (16PCD) to adulthood, the number of axons in the optic nerves were estimated from sample areas totalling 1-12% of the cross-sectional area of the nerve. On the 16PCD there are about 20,000 axons in the optic stalk. The number of axons in the retrobulbar part of the optic nerve reaches a peak value of 766,000 on the 23PCD, and then decreases to about 350,000 by the 32PCD (the day of birth). The number of axons does not change between the 32PCD and 50PCD, but thereafter it slowly decreases, reaching the adult number (294,000) by the 84PCD. A similar trend is apparent in pigmented animals. Thus, on the 25PCD there are 736,000 axons in the retrobulbar part of the optic nerve and the number decreases to 428,000 by the 31PCD. In the adult pigmented rabbit there are 280,000 axons in the optic nerve. In animals younger than the 32PCD, growth cones are present, and the number of axons in the prechiasmal part of the optic nerve was 8-22% lower than in the retrobulbar part of the same nerve. These observations suggest that there is a continued outgrowth of axons from the eye towards the target nuclei. By the 32PCD, the numbers of axons in the retrobulbar and prechiasmal parts of the nerve were very similar, suggesting that by this age all axons had reached the chiasm. The numbers of retinal ganglion cells (RGCs) labelled by massive injections of horseradish peroxidase into the retino-recipient nuclei were estimated in albino rabbits aged from the 24PCD to adulthood. RGCs were counted in evenly spaced sample areas totalling 4-11% of the retinal area. On the 24PCD, the number of labelled RGCs (500,000) was lower than the number of axons in the optic nerve (probably because not all RGC axons had reached their target nuclei by this age). However, by the 27PCD the number of labelled RGCs (550,000) was very similar to the number of prechiasmal axons (568,000). At all ages thereafter, the numbers of both RGCs and axons were very similar, with adult RGC numbers (about 291,000) being reached by the 85PCD. We conclude that axon loss in the rabbit optic nerve after the 27PCD is almost certainly due to the elimination (presumably death) of the parent RGCs, and we suggest that RGC death is also the most likely cause of axon loss prior to the 27PCD.(ABSTRACT TRUNCATED AT 400 WORDS)     

Changes in axon arrangement in the retinofugal [correction of retinofungal] pathway of mouse embryos: confocal microscopy study using single- and double-dye label

The changes in quadrant-specific fiber order in the retinofugal pathway of the C57-pigmented mouse aged embryonic day 15 were investigated by using single- (1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate; DiI) and double- (N-4-4-didecylaminostyryl-N-methylpyridinium iodide; 4Di-10ASP in addition to DiI) labeling techniques. At this earliest stage of development, before any fibers arrive at their targets, retinal axons display a distinct quadrant-specific order at the optic stalk close to the eye. This order gradually disappears along the stalk and is virtually lost at the chiasm, as shown in single-label preparations. The double-label preparations, in which the population peaks of fibers from two retinal quadrants are shown simultaneously in an image, show a fiber arrangement at the chiasm that is different from the pattern seen in the single-label preparations. A distinct and consistent preferential distribution of fibers from different retinal quadrants is shown in the chiasm. Before the midline, the central part of the cross section of the chiasm is dominated by dorsal fibers, whereas the rostral and caudal parts of the chiasm are dominated by ventral nasal and ventral temporal fibers, respectively. Moreover, the double-label preparations demonstrate a major reshuffling of fiber position after the fibers cross the midline. Fibers from ventral retina are shifted gradually to a rostral position at the threshold of the optic tract, whereas fibers from dorsal retina are shifted caudally. These changes in fiber position indicate a postmidline location in the chiasm, where fibers are re-sorted in accordance with their origins in the dorsal ventral axis of the retina, and suggest a change in axon response to guidance signals when the fibers cross the midline of the chiasm. These changes in fiber order may also be related to the re-sorting of fibers according to their ages at the postmidline chiasm.     

Retinogeniculostriate projections in guinea pigs: Albino and pigmented strains compared

The retinogeniculate fibers and geniculocortical projections of pigmented and albino guinea pigs were studied by anatomical degeneration methods and by electrophysiological techniques. In one experiment, an eye was enucleated from each of six pigmented and six albino animals. Six to δ days later the animals were killed and the crossed and uncrossed retinal projections to the dorsal lateral geniculate nuclei studied in serial sections prepared by the Nauta silver method. An organized uncrossed retinogeniculate projection was invariably present in the pigmented guinea pig but was not seen in the albino. There was a consistency in the pattern of the crossed retinogeniculate projections among the pigmented guinea pigs but not among the albino animals. Between ocular enucleation and histological analyses, visually evoked responses at the cerebral cortex were recorded. Indications of an input to the striate cortex via noncrossing fibers were found only in the pigmented strain. A relatively consistent pattern of input to the contralateral striate cortex was observed in the pigmented guinea pigs, while several patterns were seen in the albinos.     

Prenatal development of the optic projection in albino and hooded rats

The development of retinofugal projections has been examined in albino and hooded rat embryos from embryonic day 16 to birth (E21.5). Horseradish peroxidase (HRP) was injected intraocularly through the uterine wall and its anterograde transport revealed with TMB and DAB. The retrograde transport of HRP or the fluorescent dyes Nuclear yellow, Fast blue and propidium iodide from optic tract, superior colliculus (SC) or lateral geniculate body (LG) injections was used to demonstrate the origin of the projections. Superficial projections to the contralateral SC were first identified at E16. A light projection to the entire medio-lateral extent of the ipsilateral SC could be detected a day later. The optic axons grow over the surface of the diencephalon at E16 and it was only at later stages that the fibers were observed to invade successively deeper parts of the LG. A superficial projection to the ipsilateral LG could first be detected at E17. Both the ipsilateral and contralateral projections grew through the entire dorso-ventral extent of the lateral geniculate body: some restriction of the axons to their normal adult termination zones could be detected by E21. No difference in the distribution of projections could be detected between the albino and pigmented rats although the projections were lighter, and possibly because of this were detected later, in the albino rats. At all the ages examined in this study labeled retinal ganglion cells were observed in the non-injected eyes after injection of label into the contralateral eye. The use of persistent fluorescent dyes showed that these retinal ganglion cells did not survive for more than 5 days postnatally. The projection to the uninjected eye came preferentially from ganglion cells in the lower nasal retina while the ipsilateral central projections came predominantly but not exclusively from the lower temporal retina of the injected eye. It appears, therefore, that the initial projections of optic axons in the rat are not limited to their normal termination zones and that the choice of pathway at the chiasm appears to be only loosely controlled.