Retinopretectal projections in albino and pigmented rabbits: an autoradiographic study

The ipsilateral and contralateral retinal projection was studied in pigmented rabbits and in 3 strains of albino rabbits by anterograde transport of [3H]proline and [3H]fucose combined with autoradiographic techniques. Special attention was paid to the terminals in the pretectal area of both the pigmented and albino strains. On the contralateral side terminal labeling was found in both pigmented and albino rabbits in the nucleus of the optic tract (NOT), the anterior pretectal nucleus (PA), the posterior pretectal nucleus (PP) and the pretectal olivary nucleus (PO). Ipsilaterally labeling was found only in the pigmented strain in small patches in the PP. Ipsilateral projection was not found in the albinos in the pretectal area. The results are in agreement with the findings of Scalia in pigmented rabbits. The absence of ipsilateral labeling in the pretectal region in albinos is in contrast with earlier findings of Giolli and Takahashi et al., in pigmented rabbits but is in agreement with the observations of Takahashi and Oyster. Since no radioactively labeled fibers were found to project to the NOT in either pigmented or albino rabbits, these results do not support the hypothesis of Collewijn that the inverted optokinetic nystagmus in albinos is due to misrouting of the ipsilateral retinal fibers to the NOT.     

Origins of crossed and uncrossed retinal projections in pigmented and albino mice

The extent of the binocular cortical field in albino mice, as revealed by recording from single cells, was almost normal; although the input from the ipsilateral eye was weaker than normal, most cells were driven from both eyes. By backfilling retinal ganglion cells from one optic tract with horseradish peroxidase we examined the origins of the retinofugal projections. Filled cells ipsilateral to the injected tract were concentrated in a crescent-shaped area bordering the inferior temporal retina. In black mice this area constituted 20% of the total retinal area, in albinos 17%. In black mice we counted nearly 1,000 labeled cell in the ipsilateral retina, or 2.6% of all cells filled in both eyes. Albinos had about one-third fewer filled cells ipsilaterally than black mice. Four percent of all ipsilaterally filled cells in black mice and 8% in albinnos were scattered outside of the crescent region. The density of ipsilaterally projecting cells was uniform throughout the crescent region in black mice, but decreased toward the central retina in albinos. In retinas contralateral to the injection up to 39,000 cells were filled—about two-thirds of the cells in the ganglion-cell layer whose cytoplasm contained conspicuous Nissl substance. Depending on classification of unfilled cells as ganglion cells or interneurons, we estimated a total 48,000 to 65,000 ganglion cells to exist in the retina. The size distribution of ipsilateraly projecting ganglion cells was similar in albinos and normals. Ipsilaterally projecting ganglion cells were on average 1.8–3 times larger in volume than contralaterally projecting ones in both types of mice. Displaced ganglion cells were relatively more common in ipsilateral retinofugal projections: 21% of all ipsilateral ganglion cells were displaced versus less than 1% of all the contralateral ganglion cells in black mice. In albinos only 13% of the ganglion cells in the ipsilateral retina were displaced. The overall reduction in ipsilaterally projecting cells in albinos was reflected twice as much in displaced ganglion cells as in normally placed ones.     

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.     

Genetic control of retinal projections in inbred strains of albino mice

Mutations in the tyrosinase gene are often associated with a misrouting of retinal ganglion cell axons at the optic chiasm. In albinos, tyrosinase activity is lost and some ganglion cell axons that would normally project into the ipsilateral optic tract instead cross midline and project into the contralateral tract. The developmental mechanisms that cause this modification in neuronal connectivity are unknown. In this study, we screened six diverse strains of albino mice (strains 129, A, AKR, BALB/c, C57BL/6-c/c, and CD-1) to discover genetically determined variations and possible gene loci that might affect the severity of the albino decussation abnormality. Ganglion cells were retrogradely labeled with horseradish peroxidase, and the ipsilaterally and contralaterally projecting cells were counted. The average number of ipsilaterally projecting ganglion cells in the six albino strains varies from 1,000 to 1,300. Despite this variation, 1.8–1.9% of the total population projects ipsilaterally in each strain. In comparison, 2.8% project ipsilaterally in the pigmented strain, C57BL/6-+/+. However, the percentage of displaced, ipsilaterally projecting cells varies substantially among albino strains-from a low of 4% in strain CD-1 to a high of nearly 10% in C57BL/6-c/c. We conclude that even with large differences in genetic background and in absolute numbers of ganglion cells, there is no appreciable variation in the magnitude of decussation error among albino mice. The consistent effect of null alleles at tyrosinase suggests a comparably tight linkage between the biochemical activity of this enzyme and the mechanisms that control decussation phenotype. © 1995 Wiley-Liss, Inc.     

Sprouting of ipsilateral retinal projections in the optic system of the albino rat

Tritiated fucose, when injected into the eye of the rat, is incorporated into glycoprotein and transported by axoplasmic flow to regions of the brain which receive retinal projections. After injection of this substance into the remaining eye of albino rats unilaterally enucleated 3 to 4 months previously, label can be observed over the medial terminal nucleus on sides ipsilateral as well as contralateral to the injected eye. In these preparations, no label could be seen over the dorsal terminal nucleus or the latral terminal nucleus of the ipsilateral side. In unenucleated rats unilaterally injected intraocularly with fucose, the presence of silver grains over the medial terminal nucleus of the ipsilateral side was not observed. These results support the existence of an ipsilateral projection into the medial terminal nucleus of the accessory optic system and provide additional evidence that retinal fibers of the adult rat are capable of sprouting in response to denervation.     

The organization of the retinal projection to the dorsal lateral geniculate nucleus in pigmented and albino rats

The retina maps over the dorsolateral and posterior surfaces of the contralateral dorsal lateral geniculate nucleus of albino and pigmented rats, such that the upper retina projects posteriorly and the lower retina projects over the dorsolateral surface. Nasal retina projects ventrolaterally and temporal retina dorsomedially. From the surface, lines of projection (demonstrated after either localised retinal or visual cortical lesions) tend to run deep and anteriorly within the nucleus. The area covered by the uncrossed optic pathway differs between pigmented and albino rats. In the pigmented animals it extends no more than 60° from the edge of the visual field represented in the crossed projection, while in albino animals it extends as far as 100° or more. The uncrossed projection in the albino strains tends to be deficient posteriorly (upper retinal representation) and dorsomedially, and the overall density is less than that found in the pigmented animals. Small lesions localised in the extreme peripheral temporal retina of both albino and pigmented rats have always produced degeneration in the contralateral as well as ipsilateral geniculate, even though some of the lesions map only as far as, or within the peripheral 20° on the contralateral colliculus. Most of these lesions in the albino rats give two patches of uncrossed degeneration in the geniculate with at least one focus of degeneration in the contralateral geniculate. Those made in the lower temporal retina of the albino rat give in addition to the uncrossed patches, two areas of crossed degeneration in the geniculate separated by about 50° in terms of visual field projection. These double projection aberrations do not occur in pigmented animals. The suggestion is offered that in albino rats the retina of each eye maps totally on the contralateral lateral geniculate nucleus. However, the vertical midline of the visual field is represented at about 40–50° from the medial edge of the nucleus. A normal (but sparse) uncrossed pathway maps lateral to this position, but also maps in duplicate medial to it. In addition, it appears that some crossed axons may also be abnormal in their termination, and project to both sides of the vertical meridian. If the above interpretation is correct, the anomalies of the albino rat may derive from a confusion of attempting both field and retinotopic maps on the same nucleus. The possibility exists that a comparable total crossed retinogeniculate projection exists in pigmented animals but that the retina temporal to the vertical midline projection is restricted in its connection to a small band on the medial border of the contralateral nucleus.     

A comparison of the initial retinal ganglion cell projection to the contralateral superior colliculus in albino and pigmented rats

Newborn albino and pigmented rats received localised Fast blue (FB) injections into the most caudal part of the contralateral superior colliculus (SC). A proportion of retinal ganglion cells (RGC's) from the temporal retina which in the adult projects exclusively to the rostral half of the colliculus are labelled by injections to the caudal colliculus in neonatal animals. The majority of these cells die during the period of naturally occurring cell death in the retina, which occurs during the first 10 postnatal days. The object of this experiment was to see whether albino rats, which have well documented abnormalities in axon pathfinding in their visual system, had a larger number of cells in temporal retina which initially project to caudal colliculus than pigmented animals. On postnatal day 2 (P2), the ratio of temporal to nasal RGCs projecting to the caudal SC is greater in albino than pigmented rats (6.2% vs 2.65%). After the wave of naturally occurring cell death, at P14, when many of the neonatal errors have been eliminated, the ratio of temporal to nasal RGC's is reduced to 1.71% for albinos versus 1.53% for pigmented rats.     

The uptake of gamma-aminobutyric acid and glutamate by synaptosomes from the visual cortex of albino and pigmented rabbits

Summary The synaptosomal uptake of glutamate and gamma aminobutyric acid [GABA] in the visual cortex of albino and pigmented rabbits was compared. GABA uptake was similar in both pigmented and albino rabbits, but glutamate uptake was greater in the pigmented rabbit. The kinetics of glutamate uptake in albino and pigmented rabbits suggested that the number of functioning glutamate synapses may be lower in the albino. The significance of this with respect to the differences in visual processing in the two types of rabbit is discussed.     

Postnatal changes in retinal ganglion cell and optic axon populations in the pigmented rat

The number of ganglion cells in the retina of the postnatal rat has been examined. We estimated both the number of axons in the optic nerve and the number of cells which can be retrogradely labelled with horseradish peroxidase from injections into the brain. In the retina of the newborn rat there are at least twice as many ganglion cells as in the adult rat. By retrograde labelling of the ganglion cells and following transection of their axons 24-48 hrs later we can find no evidence that ganglion cells withdraw their axon without degeneration of the patent cell body. We have found that the excess ganglion cells are lost over the first ten postnatal days and during this period we observe pyknotic nuclei in the ganglion cell layer. From our estimates of the total number of neurones in the ganglion cell layer and the number of ganglion cells found at different ages we conclude that the migration of amacrine cells into the ganglion cell layer occurs in the first five postnatal days.     

Enlargement of uncrossed retinal projections in the albino rat: additive effects of neonatal eye removal and thalamectomy

The present study in the albino rat investigates the effects of neonatal unilateral eye removal and/or thalamectomy upon the number of ipsilaterally projecting retinal ganglion cells (IPRGCs), using retrograde fluorescent labelling and electron microscopy. The results show that neonatal unilateral eye removal and thalamectomy result in a significant increase in the number of aberrant IPRGCs as compared to that observed in normal rats, and the effects of the two different neonatal lesions appear to be additive. These findings strongly suggest that there are at least two subpopulations of IPRGCs, which normally do not exist in mature albino rats, but which can be preserved into adulthood by neonatal enucleation or thalamectomy. The data also suggest that about 70% of the entire population of IPRGCs, most of which normally exist only transiently in neonatal retinas, can be retained in rats which receive both unilateral eye removal and thalamectomy at the neonatal stage.     

GABA content in the retina of pigmented and albino rats

Reduction of the melanin precursor DOPA associated with albinism leads to spatiotemporal disturbances in retinal neurogenesis and thus seems to be responsible for numerous neuronal alterations found in albino retinae. To investigate whether these cellular alterations are reflected in retinal neurotransmitter concentrations we compared the levels of GABA and glutamate in the retina of adult pigmented Long Evans and albino Wistar rats using reversed phase-liquid chromatography (RP-HPLC). When normalized to retinal weight, GABA levels showed a statistically insignificant trend to be lower and glutamate values to be higher in albinos than in pigmented animals. The ratio of glutamate to GABA was significantly higher in albino than in pigmented retinae. As numerous studies have shown that the balance between GABA and glutamate plays a crucial role for establishing direction selectivity, these results are discussed in relation to direction selectivity and defects in the optokinetic system of albinos.     

Retinal projections in tyrosinase-negative albino cats

Retinal projections were examined in two tyrosinase-negative albino cats using autoradiographic techniques. Cats from this colony have pink eyes; their retinal pigment epithelium, ciliary body, and iris epithelium are completely devoid of melanin pigment. Test breeding for five generations indicates that these cats are true albinos (cc). The most striking feature of the albino cats' visual pathways was a reduction in ipsilateral input which was more severe than that reported for Siamese cats. The only evidence of ipsilateral input to the laminated dorsal lateral geniculate nucleus of the albino was a small lateral normal segment and a small projection to the lateral portion of lamina C1. Ipsilateral projections to the medial interlaminar nucleus, retinal recipient zone of the pulvinar complex, ventral lateral geniculate nucleus, superior colliculus, and pretectum also were reduced. Ipsilateral projections to the suprachiasmatic nucleus appeared to be normal in the albino cats studied. Our findings indicate that, compared to the normal cat as well as to the tyrosine-positive Siamese cat, the tyrosinase-negative albino has reduced ipsilateral retinal projections. The albino cat is a model system analogous to tyrosinase-negative albinism found in mammals.     

Correlation between different types of retinal ganglion cells and their projection pattern in the albino rat

Injecting Fluoro-Gold (FG) and Evans-Blue (EB) into the right dLGN and SC in the adult albino rat, ipsilaterally projecting double-labeled retinal ganglion cells were mainly seen in the ventrotemporal crescent. They were mainly large sized cells. The ipsilaterally projecting double-labeled cells tended to have larger somata than the single- and double-labeled cells projecting to the contralateral superior colliculus and/or dorsal nucleus of the lateral geniculate body.     

Developmental changes in the distribution of retinal catecholaminergic neurones in hamsters and gerbils

Although Syrian hamsters and Mongolian gerbils are closely related, they have quite different patterns of retinal ganglion cell distribution and different patterns of retinal growth that produce their distributions. We have examined the morphology and distribution of catecholaminergic (CA) neurones in adult and developing retinae of these species in order to gain a more general understanding of the mechanisms producing cellular topographies in the retina. CA neurones were identified with an antibody to tyrosine hydroxylase (TH), the rate limiting enzyme in the production of catecholamines. In adult retinae of both hamsters and gerbils, most CA somata were located in the inner part of the inner nuclear layer (INL) and CA dendrites spread in a outer stratum of the inner plexiform layer (IPL). Their somata varied with retinal position, being largest in temporal and smallest in central retina. In hamsters, but not gerbils, a small number of CA interplexiform cells was also observed. In development, CA somata of hamster retinae were observed first in the middle and/or scleral regions of the cytoblast layer (CBL) at P (postnatal day) 8. By P12, CA somata were commonly located in the inner part of the INL and their dendrites spread into the outer region of the IPL. In developing gerbil retinae, CA somata were first observed at P6 in the middle of the CBL. Over subsequent days, they migrated into the inner part of the INL and spread their dendrites into the outer strata of the IPL. In both hamsters and gerbils, CA cells were initially concentrated in the superior temporal margin of the retina. In hamsters, this supero-temporal concentration persisted until adulthood, whereas in adult gerbils, the greatest density of CA cells was found just superior to the visual streak. These distributions were distinct from those of the ganglion cells in adult and developing retinae of each species. We discuss the role of maturational expression of TH, cell death, and retinal growth in the generation of the distinct distribution of the CA cells.     

Variation in visual acuity within pigmented,and between pigmented and albino rat strains

Many researchers assume that laboratory rats have poor vision, and accordingly, that they need not consider differences in the visual function of rats as a consequence of strain or experience. Currently, it is not specifically known whether rat domestication has negatively affected the visual function of laboratory rat strains, what the effects of strain albinism are on rat visual function, or whether there are strain differences in the visual function of laboratory rats that are independent of pigmentation. In order to address these questions, we measured psychophysically the vertical grating acuity of three pigmented (Dark Agouti, Fisher-Norway, Long-Evans) and three albino (Fisher-344, Sprague-Dawley, Wistar) strains of laboratory rats, and compared their acuity with that of wild rats. The grating thresholds of Dark Agouti, Long-Evans and wild strains clustered around 1.0 cycle/degree (c/d) and did not significantly differ from one another. Fisher-Norway rats, however, had a significantly higher threshold of 1.5 c/d. The grating thresholds of Fisher-344, Sprague-Dawley, and Wistar strains, which were clustered around 0.5 c/d, were significantly lower than those of the pigmented strains. These data demonstrate that there is significant strain variability in the visual function of laboratory rats. Domestication of Long-Evans and Dark Agouti strains does not appear to have compromised visual acuity, but in the case of Fisher-Norway rats, selective breeding may have enhanced their acuity. Strain selection associated with albinism, however, appears to have consistently impaired visual acuity. Therefore, a consideration of strain differences in visual function should accompany the selection of a rat model for behavioral tasks that involve vision, or when comparing visuo-behavioral measurements across rat strains.     

Developmental changes in olfactory bulb projections revealed by degeneration argyrophilia.

The maturation of the main and accessory olfactory bulb projections to the ventral forebrain of the golden hamster has been traced by using the Fink-Heimer silver technique to stain degenerating axons and terminal arborizations after bulbectomy at different ages between birth and 33 days. In the youngest pups, long-lasting degeneration argyrophilia (LLDA) is found in two regions of prepiriform cortex: at the level of the rostral tubercle and rostral amygdala. By five days of age the caudal region exhibiting a long-lasting degeneration reaction extends from the middle of the olfactory tubercle to the middle of the amygdala. The olfactory tubercle, medial and cortical amygdala and entorhinal cortex subsequently develop substantial LLDA at ages varying between 9 and 13 days. In a previous study (Leonard, '74b) the onset of LLDA in optic tract terminals in the superior colliculus was found to coincide with the age of eye opening and the onset of a stage of rapid snyapse formation. Since different olfactory responses appear at different times during the golden hamster pup's first two weeks of postnatal life, it seems possible that the onset of LLDA in different regions of the olfactory projection at different ages may be related to the onset of different specific olfactory functions.     

Analysis of the retinohypothalamic tract in congenic albino and pigmented rats

To determine whether differences in the retinohypothalamic tract (RHT) were related specifically to albinism, we analyzed the distribution and trajectory of this pathway in congenic F344-c/+ albino and pigmented rats using the inactive subunit of cholera toxin conjugated to horseradish peroxidase as an anterograde tracer. We found that the overall volume of the tract in the albino rats was greater than in the pigmented rats (P < 0.05). We also noted shape differences.     

GABA-immunoreactive starburst amacrine cells in pigmented and albino rats

In this study we tested whether the critical anatomical substrate for retinal direction selectivity is altered in albino mammals. We used dual immunostaining for GABA and choline acetyltransferase and quantitatively analyzed the number of double-labelled starburst amacrine cells in wild-type and albino rats. In albino rats, the percentage of ON-amacrine cells with high GABA content was significantly lower than in pigmented animals. OFF-amacrines did not significantly differ between the two rat strains. Thus, the decreased GABA content in ON-amacrine cells could reflect an altered neuronal substrate for retinal direction selectivity. These results are discussed in relation to the optokinetic deficits described in albino mammals.     

Developmental changes of pattern reversal visual evoked potentials

Analysis of developmental changes in pattern reversal visual evoked potentials (PVEPs) was performed on 141 normal children ranging in age from 1 month to 19 years 4 months. The stimulus was a black and white checkerboard pattern on a television screen, and the check edge subtended 50 min of retinal arc. The major positive peak (P2) was observed in all subjects, and the incidence of other peaks tended to increase with age. The P2 latency decreased rapidly during the first six months of life and reached a constant value after the age of 2 years. The P2 latency with monocular stimulation was significantly longer than that with binocular stimulation in most age groups. Developmental changes of the N1-P2 or P2-N2 amplitudes were unclear, and the standard deviation of the amplitude in each age was too large for clinical application. The P2 latency with binocular stimulation was shorter for females than for males only at the age of 8-11 years.