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PubMed1996

Neurochemical architecture of the normal and degenerating rat retina.

We used post-embedding immunocytochemistry to determine the cellular localization of glutamate, gamma-amino butyric acid (GABA), glycine, aspartate, glutamine, arginine, and taurine in the normal and degenerating rat retina. Müller's cell function was also evaluated by determining the uptake and degradation characteristics for glutamate. Immunocytochemical localization of amino acids in adult Royal College of Surgeons (RCS) and control rat retinas were similar with respect to cell classes. Differences in the intensity of labelling for glutamate, aspartate, glutamine, and glycine were observed in several classes of neurons, but the most prominent differences were shown by bipolar cells of the adult RCS rat retina. In addition, glutamine labelling within Müller's cells was higher in the RCS rat than the control. These changes may have occurred because of alterations in the glutamate production or degradation pathways. We tested this hypothesis by determining Müller's cells glutamate uptake and degradation characteristics in adult and postnatal day 16 RCS retinas. High affinity uptake of 3[H]-glutamate revealed an accumulation of grains over Müller's cell bodies in the adult RCS retina implying glutamate degradation anomalies. We confirmed anomalies in glutamate metabolism in RCS Müller's cells by showing that exogenously applied glutamate was degraded over a longer time course in postnatal day 16 RCS retinas, compared to control retinas. Differences in arginine immunoreactivity in adult and immature RCS retinas conform to the presumed dysfunction of Müller's cells in these degenerating retinas. The anomalies of amino acid localization, uptake and degradation lead us to conclude that Müller's cells in the RCS retina show abnormal function by postnatal day 16; an earlier time to previously reported anatomical and functional changes in this animal model of retinal degeneration.

Amino Acids↗
PubMed2004

The role of opsin expression and apoptosis in determination of cone types in human retina.

In primates, short wavelength sensitive cones (S cones) and medium- or long-wavelength-sensitive cones (L/M cones) are two separate populations. Each cone type has a different developmental timecourse, contributes to different intra-retinal circuits, and transmits different types of information to the brain. However, in fetal human retina a significant population of cones express both S and L/M opsin (S+L/M cones), raising questions about whether S+L/M cones die or change opsin expression during development. We have utilized fetal, postnatal and adult human retinae to study the immunohistochemical distribution and morphology of S+L/M cones during development. Because S cones appear to be at higher density in fetal compared to adult retinae, we used antibodies to S opsin and alpha-transducin to estimate the proportion of S-cones, and TUNEL labelling to detect apoptotic death in the L/M, S or S+L/M population during development. S cones were present in central retina from fetal week (Fwk)11 and covered the retina by Fwk20. L/M cones appeared in the foveal cone mosaic 3-4 weeks after S-opsin was first detected, and covered the retina by birth. S+L/M cones were detected in all retinae older than Fwk14. They were most numerous at the retinal eccentricity where L/M opsin was just appearing; i.e. at the 'front' of L/M opsin expression. In this region, five morphological types of cones were present. (1) Heavily labelled S cones had thick cell bodies, a thick basal axon and pedicle, and a nucleus at any level of the outer nuclear layer (ONL). (2) Heavily labelled L/M cones were wine goblet shaped with a small round cell body, a large nucleus at the outer ONL edge, and a thin axon with a prominent synaptic pedicle. (3) Goblet-shaped S+L/M cones. (4) Goblet-shaped cones lightly labelled for S-opsin. (5) Cones that were not immunoreactive to either opsin. Only type 1 S cones were present peripheral to the L/M expression front, and their labelling intensity, morphology and distribution indicates that these are the 'true blue' cones of the adult mosaic. Only type 2 L/M cones were present in the foveal cone mosaic. Types 3 and 4 were most numerous within 500-750 microm of the L/M expression front, but type 3 S+L/M cones were also scattered throughout more central regions in fetal, infant and adult retinae. S+L/M cones comprised 5-10% of opsin immunoreactive cones at the L/M front in fetal and early postnatal retinas but 0.01-0.03% throughout P8mo and adult retinae. We found no evidence of significant levels of apoptosis in L/M cones at the expression front, suggesting that this decrease was not due to cell death. The findings suggest that goblet-shaped cones destined to express L or M opsin may initially and transiently express S opsin. Near the optic disc, at Fwk17 S cone density was around 2000 cells mm(-2), which dropped 50% by Fwk20 and stabilized at around 500 cells mm(-2) by birth. Double labelling with alpha-transducin showed that throughout this period 8-10% of all cones expressed S opsin. TUNEL labelling found no significant apoptosis in the S cone population. The decrease in S cone density near the optic disc occurs in the absence of apoptosis, and is likely due to other developmental events acting on the photoreceptor layer, including displacement of cones towards the fovea.

Adult↗
PubMed1998

The embryogenesis of rod photoreceptors in the teleost fish retina, Haplochromis burtoni.

Development of the retina, like that of other tissues, occurs via an orderly sequence of cell division and differentiation, producing the functional retina. In teleost fish, however, cell division and differentiation in the retina continue throughout the life of the animal in two distinct ways. Stem cells in a circumferential germinal zone at the periphery of the retina give rise to all retinal cell types and progenitor cells located throughout the retina in the outer nuclear layer (ONL) produce new rod photoreceptors. These processes in adult retina recapitulate in space the embryonic events responsible for forming the retina. Analysis of these events in an African cichlid fish, Haplochromis burtoni, confirmed that cone photoreceptors differentiate first, followed by rod photoreceptors. Correspondingly, at the margin of the eye, cone photoreceptors differentiate nearer to the margin than do rods. Control of photoreceptor production is not understood. Here we present the time of appearance and distribution pattern of GABA and vimentin which are candidates for the control of retinal cell division and differentiation. Antibody staining reveals that both GABA and vimentin exhibit unique patterns of expression during embryonic retinal development. Vimentin immunoreactivity is evident throughout the retina in a spoke-like pattern between developmental Days 4 and 7, as both cone and rod photoreceptors are being formed. GABA is expressed in horizontal cells between Days 5 and 7, corresponding to the onset of rod differentiation in time and in position within the retina. Moreover, the wave of GABAergic staining in the horizontal cells parallels the wave of rod differentiation across the embryonic retina of H. burtoni. Thus, GABA may play a role in the development of rod photoreceptors.

Animals↗
PubMedDate not supplied

Distribution of photoreceptor types in the retina of a marsupial, the tammar wallaby (Macropus eugenii).

Mammalian retinae generally contain low numbers of short-wavelength-sensitive cones (S-cones) and higher numbers of middle- to long-wavelength-sensitive cones (M-cones). Some recent studies found topographic differences between the different photoreceptor types and in some instances between photoreceptors and ganglion cells. To investigate this question further, we constructed topographical maps of the different photoreceptors found in an Australian marsupial, the tammar wallaby. We used two polyclonal antibodies that have been shown to label S-cones (JH455) or M-cones (JH492) in a range of mammals. In the tammar wallaby, the antisera clearly distinguish two cone types. JH455 recognizes a small subset of cones (S-cones) with a density of less than 500 cells/mm2 in the ventral retina. Their density increases towards the dorsal retina to about 1600-2000 cells/mm2. JH492 recognizes all remaining cones (M-cones), but also faintly labels most cone cells recognized by JH455. The distribution of M-cones, unlike that of the S-cones, shows a clear horizontal streak of high cell density through the central retina, just like the ganglion cells. Unlike the ganglion cells, however, the M-cones do not peak in the temporal retina but show a very broad peak (12,000-18,000 cells/mm2) in the central or even slightly nasal retina. Based on our findings, the retina of the tammar can be divided into three distinct regions: firstly, the dorsal retina, which has a low ganglion and low cone cell density but a high percentage of S-cones (30%), is thought to provide good spectral sensitivity; secondly, the central horizontal band of retina, which has a high ganglion and high cone cell density and therefore provides good spatial resolution; and thirdly, the ventral retina, which has a low ganglion cell but high cone cell density with few S-cones (5%) and is therefore thought to have a high contrast sensitivity but low acuity.

Animals↗
PubMed1988

Modulation of cone horizontal cell activity in the teleost fish retina. III. Effects of prolonged darkness and dopamine on electrical coupling between horizontal cells.

The effects of prolonged darkness and dopamine on the coupling between horizontal cells in the isolated, superfused white perch retina were studied. Two assays of coupling were employed; area versus amplitude relationships (area-response curves) and the diffusion of the fluorescent dye Lucifer yellow from intracellularly injected cells to neighboring cells. In prolonged dark-adapted retinas, area-response curves were difficult to determine because of the small light responses; however, light-evoked responses did not increase in size when light spots were larger than 0.8 mm in diameter. Following the presentation of dim background illumination that partially sensitized the retina, responses to light spots of various sizes were enhanced and an area-response curve could be constructed. Subsequent presentation of moderate background illumination that more fully sensitized the retina resulted in reduced responses to small spots (less than 1.6 mm in diameter) and enhanced responses to large spot or full-field stimuli. In retinas exposed to moderate background illumination, Lucifer yellow injected intracellularly into cone horizontal cells diffused into many neighboring horizontal cells. The coupled cells were very similar in morphology, suggesting they were of the same type. In prolonged dark-adapted retinas, on the other hand, the dye was usually restricted to the injected cell and a few adjacent cells. These results indicate that coupling between cone horizontal cells is modulated by prolonged darkness and background illumination. Following dopamine (50 microM) application, in both 6-OHDA-treated and untreated retinas, changes in area-response curves of cone horizontal cells were observed just opposite to those that occurred when prolonged dark-adapted retinas were exposed to background illumination. That is, following 5 min application of dopamine to the retina, responses to small spots (less than 2 mm in diameter) increased in size while responses to larger spots decreased in amplitude compared with control responses. Following 20 min of superfusion with dopamine, the recorded responses were very small, and an accurate area-response curve could not be determined. Following dopamine application to light-sensitized retinas, Lucifer yellow was restricted to the injected cells or to the injected cell and a few neighboring cells. The results suggest that the modulation of coupling between cone horizontal cells by prolonged darkness and background illumination may be mediated by dopamine. Spatial properties of rod horizontal cells were also examined.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Photocoagulation does not ablate angiogenic markers in rabbit retina.

Panretinal photocoagulation (PRP) in rabbits produces treatment areas consisting of destroyed outer retina and intact inner retina separated by areas of normal-appearing retina. Intravenous iodoacetate produces widespread destruction of the outer retina with sparing of the inner retina, approximating total, confluent PRP. After PRP (at three weeks), intravenous injection of iodoacetate (at three weeks or four months), and in control rabbits, eyes were harvested and retinas were homogenized in a balanced salt solution. Retinal homogenates were measured for three markers of angiogenic activity: vascular endothelial cell migration, proliferation, and production of plasminogen activator. Retinas subjected to PRP or intravenous iodoacetate (at three weeks or four months) stimulated migration and proliferation above baseline levels twice as much as control retinas and stimulated plasminogen activator production by twofold to 2.5-fold. These data suggest that PRP does not eliminate the ability of the retina to produce angiogenic activity, but rather exerts its antiangiogenic effect in an indirect fashion.

Animals↗
PubMed1997

Localisation of amino acid neurotransmitters during postnatal development of the rat retina.

We used postembedding immunocytochemistry to determine the localisation of the amino acid neurotransmitters glutamate, gamma-aminobutyrate (GABA), and glycine, potential neurotransmitter precursors (aspartate and glutamine), and taurine in the rat retina during postnatal development. All amino acids investigated were present at birth; however, only the inhibitory neurotransmitters GABA and glycine displayed neuronal localisation. GABA was localised in a sparse population of amacrine cells, and glycine immunoreactivity was found in cells within the ventricular zone that appeared to migrate through the neuroblastic layer. Glutamate labelling was diffuse across the retina until postnatal day (PND) 8. Localisation of glutamine was evident within Müller's cells by PND 6, in agreement with the known age of onset of glutamine synthetase activity. Based on the findings of uptake of radiolabelled glutamate and GABA by PND 8 and changes in immunoreactivity, we propose that Müller's cells evolve at PND 6-8 from their precursor cells, the radial glial cells. Evidence for differences in glutamate turnover in the infant retina was seen on examination of aspartate and glutamine immunoreactivity. Aspartate labelling was weak until PND 11, when ganglion cells and some amacrine cells were labelled. Unlike the mature retina, a large number of amacrine cells were glutamine immunoreactive in the PND 6 retina. One reason for the observed differences in precursor pooling may be a lack of neuronal neurotransmitter release and overall low metabolic activity. We also investigated the response of the developing retina to ischaemic insult to test the physiological hypoxia model of vascular development. Our findings are consistent with the hypothesis that the developing retina has increased tolerance to ischaemic insult. Our findings suggest that, although the retina is morphologically adult like by PND 8, there are differences in neurotransmitter turnover in the immature rat retina.

Amino Acids↗
PubMed1979

Topographic organization of the projections of the retina to the pretectal region in the rat.

The pattern of projection of the retina to the pretectal region and its retinotopic organization were investigated in the rat by autoradiographic and silver impregnation techniques for axonal pathways. The endings of retinal axons form three terminal fields in the pretectum in: 1, olivary pretectal nucleus (PO), bilaterally; 2, posterior pretectal nucleus (PP), bilaterally; and 3, nucleus of the optic tract (NTO), contralaterally. The following retinotopic pattern was observed in rats surviving peripheral retinal lesions and injections of 3H-proline in the same eye, when the positions occupied by terminal degeneration in Fink-Heimer stained sections were matched with the corresponding areas deficient in radiolabel in adjacent autoradiographic sections showing the surviving parts of the terminal fields. The nasal periphery of the retina maps along the adjoining edges of PO and PP, both of which extend obliquely, in a posterolateral direction, through the entire extent of the pretectum. Both nuclei map the line of representation of the anterior midline (in the temporal retina) along their opposite edges (anterolaterally, in PO; posteromedially, in PP). This mirror-image symmetry is completed by the representation of the ventral peripheral retina separately in the rostral poles and the dorsal peripheral retina separately in the caudal poles of both nuclei. The map in NTO is vertically oriented, with the temporal retina, dorsally, the nasal retina, ventrally, the ventral retina, rostrally, and the dorsal retina caudally represented. The binocular area of the terminal field in PO is subdivided by a terminal-free zone into two parts that may process separately events in the central and lateral visual field.

Animals↗
PubMed1985

Distribution and immunoreactivity of glia in the retina of the rabbit.

Glial markers, namely antibodies to glial fibrillary acidic protein (GFAP), vimentin, galactocerebroside (GC), and 08 antigen, were used to study the occurrence and location of neuroglial cells in adult rabbit retinae. Müllerian glia were vimentin-positive, lacked detectable amounts of GFAP, and were found in all parts of the rabbit retina. The neuronal A-type horizontal cells were labeled by vimentin antibody only in the superior retina and at the medullary rays but not in the inferior retina. They lacked GFAP in all regions. Astroglia showing GFAP and vimentin immunoreactivity were absent from most of the superior and inferior retina, being found only in the myelinated area of the ganglion cell axon bundles, the medullary rays. Thus the rabbit retina differs from the retinae of all mammals studied to date by this restriction of astroglia to just one area. The medullary rays, which are known to be myelinated, were labeled by the antibodies to GC and 08 antigen. Boycott and Hopkins ('84) found, using whole-mounted rabbit retinae stained by the reduced silver method of Richardson, that all neurons in the ganglion cell layer of the rabbit retina have a cilium, while cells that have only a diplosome are either neuroglia or microglia. By using this criterion as a basis to differentiate between neurons and glia, the absence of neuroglia from the nerve fiber layer outside the medullary rays was confirmed in the same silver-stained material. Thus, the data obtained from immunocytochemistry and conventional silver staining agree closely. It has been concluded that, at least in the adult, significant lengths of ganglion cell axons extend without astroglial sheaths.

Animals↗
PubMed1991

Expression of glial fibrillary acidic protein by Müller cells in rd chick retina.

Accumulation of glial fibrillary acidic protein (GFAP) in Müller cells has been observed in retinas of several mammalian species secondary to genetically induced degeneration and neuronal injury. In the present series of experiments, I have examined the effects of the rd (retinal degeneration) mutation on the expression of GFAP in retinas of chicks homozygous for the mutation (rd/rd) prior to and following the onset of photoreceptor degeneration, which first appears approximately 7 days posthatch (7 dph). Carrier (+/rd) and wild-type (+/+) retinas served as controls. Retinas taken from 1, 7, 21, and 33 dph rd/rd, +/rd, and +/+ chicks were analyzed for the presence of GFAP by immunocytochemical and SDS-PAGE/Western blot techniques. The following immunocytochemical observations were made: (1) GFAP immunostaining was limited to and located throughout the Müller cells. (2) The intensity of GFAP immunostaining increased with age in all three retina types in tissue sections, as well as on immunoblots. (3) The distribution of GFAP staining within rd/rd Müller cells following the onset of degeneration was slightly different from that observed in +/+ and +/rd retinas and was distinguished by increased staining of the cell bodies and the cell processes forming the outer limiting membrane. The results of these experiments show that Müller cells in chick retina contain GFAP. In addition, they suggest that, in contrast to Müller cells in degenerating mammalian retina, Müller cells in rd chick retina do not accumulate large amounts of GFAP in response to degeneration.

Animals↗
PubMed1992

Neurons of the human retina: a Golgi study.

Golgi techniques have been applied to post mortem specimens of human retina. Analysis was possible on 150 human retinas processed and viewed by light microscopy as wholemounts. Camera lucida drawings and photography were used to classify the impregnated neurons into 3 types of horizontal cell, 9 types of bipolar cell, 24 basic types of amacrine cell, a single type of interplexiform cell, and 18 types of ganglion cell. We have distinguished two types of midget bipolar cell: fmB (flat) and imB (invaginating). In central retina, both types are typically single-headed, each clearly contacting a single cone. Peripherally, they may be two- or even three-headed, obviously contacting more than one cone. Two types of small-field diffuse cone bipolars occurring as flat and invaginating varieties are found across the entire retina from fovea to far periphery. The single rod bipolar type appears about 1 mm from the fovea and increases in dendritic tree diameter from there into the far periphery. The putative "ON-center" blue cone bipolar and the giant bistratified bipolar first described by Mariani are also present in human retina and we add two previously undescribed bipolar cell types: a putative giant diffuse invaginating and a candidate "OFF-center" blue cone bipolar. Taking into account the variation of cell size with eccentricity at all points on the retina, we observed three distinct varieties of horizontal cell. The HI is the well known, long-axon-bearing cell of Polyak. HII is the more recently described multibranched, wavy-axoned horizontal cell. The third variety, HIII, introduced here, has been separated from the HI type on morphological criteria of having a larger, more asymmetrical dendritic field and in contacting 30% more cones than the HI at any point on the retina. Amacrine cells proved to be most diverse in morphology. Many of the amacrine cell types that have been described in cat retina (Kolb et al., '81: Vision Res. 21; 1081-1114) were seen in this study. Where there are no equivalent cells in cat, we have adopted the descriptive terminology used by Mariani in monkey retina. Thus eight varieties of small-field amacrines (under 100 microns dendritic trees), eight varieties of medium-field cells (100-500 microns dendritic span), and eight large-field varieties (over 500 microns dendritic trees) have been classified. Often a broadly described variety of amacrine cell can be subdivided into as many as three subtypes dependent on stratification levels of their dendrites in the inner plexiform layer.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Role of the neural retina in newt (Notophthalmus viridescens) lens regeneration in vitro.

Removal of the lens from the eye of an adult newt (Notophthalmus viridescens) is followed by regeneration of a new lens from the dorsal iris epithelial cells at the pupillary margin. This process is dependent upon the neural retina for its normal completion in vivo and in vitro. To examine the relationship between the retina and lens regeneration, we have conducted experiments that delimit the time period during which the retinal presence is critical (in vivo) and have investigated the influence of extracts of the retina on the progress of regeneration (in vitro). In vivo, removal of the retina at day 11 seriously retards further progression of regeneration while removal of the retina at day 15 does not retard regeneration significantly. This defines a "critical period" in regeneration of the lens during which the retina is required. Explantation of regenerates 11 or 12 days after lentectomy to organ culture medium enriched with either crude retinal homogenate or extracts prepared from chick or bovine retinas according to Courty et al. ('85, Biochimie, 67:265-269) reveals that the progress of regeneration can be supported in culture by the crude extract. This is the first demonstration of complete iris-lens transformation in culture in the presence of retinal extract. It is possible that the retina acts indirectly by promoting passage of the iris epithelial cells through the critical number of mitoses required before redifferentiation into lens cells can occur (as proposed by Yamada, '77, Monogr. Dev. Biol., 13:126). It is also possible that the retina acts by directly instructing the iris cells to redifferentiate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Effects of exogenous FGF-1 treatment on regeneration of the lens and the neural retina in the newt, Notophthalmus viridescens.

Experiments were designed to compare the effects of recombinant newt fibroblast growth factor-1 (rnFGF-1) and recombinant human glial growth factor (rhGGF) on lens and retina regeneration in the eyes of adult newts. Both eyes were retinectomized and lentectomized. Beginning 3 days after the operation, one eye was given either 0.1 microg of rnFGF-1 or 0.1 microg of rhGGF in 1 microl of phosphate-buffered saline (PBS) per injection, three per week. Contralateral operated eyes served as controls and were treated with PBS alone or were not injected. In eyes that were not injected, injected with PBS alone, or with PBS containing rhGGF, regeneration of both the retina and the lens proceeded normally as described in the literature. In these control eyes, the entire retinal pigmented epithelium (RPE) depigmented/dedifferentiated and a retina rudiment formed from which a new retina regenerated by the end of the experiment at day 41 post-operation. Likewise, only a small area of dorsal iris depigmented/dedifferentiated and formed a lens vesicle from which a lens subsequently regenerated. The vitreous remained relatively free of loose cells. In eyes given rnFGF-1, the RPE depigmented/dedifferentiated and formed what appeared to be a retina rudiment but a new retina did not regenerate. Instead, vesicles were seen associated with the retina rudiment. In eyes given rnFGF-1, both the dorsal iris and ventral iris depigmented/dedifferentiated and lens regeneration occurred but the new lenses had abnormal fiber cells and the lens epithelium was very thin or absent. In addition, ectopic lenses usually regenerated in rnFGF-1-treated eyes. An abundance of loose cells were present in the vitreous of rnFGF-1-treated eyes associated largely with the RPE and the dorsal and ventral irises. The results are consistent with the view that the timely expression of FGFs is involved in the depigmentation/dedifferentiation of the RPE and dorsal iris and is necessary for proper regeneration of the lens and neural retina. Continued presence of FGF results in continued and excessive dedifferentiation, resulting in the lack of retina regeneration and abnormal lens regeneration.

Animals↗
PubMed1982

Development of the crayfish retina: a light and electron microscopic study.

The development of the crayfish retina was examined in embryos and first, second and third instars with both and light and electron microscope. Light microscopic observations indicate that differentiation begins at the posterior portion of the optic disc and progresses in an anterior direction. Development of screening pigment, dioptric elements, and rhabdoms all parallel this posterior to anterior gradient in the retina. Tracer studies in early embryos reveal that the retina is separated from the proximal neuropil regions by a distinct vascular space. This observation suggests that the source of new cells for the retina may not be the more proximal cell proliferation zone as previously indicated. It is proposed that mitotic activity within the retina and/or differentiation of cells from the anterior surface layer of the eye may be sources for addition of new cells to the retina. Proto-ommatidial clusters of seven retinula cells occur very early at the posterior region of the embryonic retina. Initially the receptor cells extend throughout the entire thickness of the retina, but later they withdraw from beneath the cornea to occupy only the proximal portion of the retina. Microvilli of the rhabdom arise from the centrally opposed membranes of the retinula cells in each cell cluster. Each new microvillus contains a core of fine filaments which extend out into the cytoplasm at its base. As development of the microvilli continues, the core filaments appear to be lost or altered, but the cytoplasmic bundles at the base of the microvilli persist.

Animals↗
PubMed1993

Synaptic and photoreceptor components in retinal pigment epithelial cell transplanted retinas of Royal College of Surgeons dystrophic rats.

Plexiform layer synaptic and photoreceptor cell components were investigated in retinas of Royal College of Surgeons (RCS) dystrophic rats transplanted with normal retinal pigment epithelial (RPE) cells by immunocytochemistry using previously characterized monoclonal antibodies. In retinas of normal adult rats and RPE-cell transplanted retinas of 4 month-old RCS rats, HNK-1, a marker for a carbohydrate of the neural cell adhesion molecule (N-CAM), was detected immunocytochemically in the inner and outer plexiform layers and ganglion cell bodies and their axons. HNK-1 was also detected in the inner plexiform layer of nontreated retinas of 4 month-old RCS rats, but was reduced to scattered patches in the outer plexiform layer. In addition, immunoreactivity for the SVP-38 antibody recognizing synaptophysin was found in both plexiform layers of normal adult rat retinas and RPE-transplanted retinas of 4 month-old RCS rats. Furthermore, photoreceptor cell bodies and their inner and outer segments were immunostained for the opsin monoclonal antibody RET-P1 in retinas of normal adult rats and RPE-cell transplanted retinas of 4 month-old RCS rats. However, in nontreated retinas of 4-month-old RCS rats, only immunostained debris material was detected. These results strongly suggest that normal RPE transplants not only rescue photoreceptor cells in RCS rats, but also maintain an essential functional capacity, in this case, synaptic components in the plexiform layers.

Animals↗
PubMed2002

Retina dorsal/ventral patterning by Xenopus TBX3.

Although it is well known that patterning in the retina of vertebrates is essential for retina formation and for the retinotopic projection of axons in the embryo, knowledge of molecular and cellular mechanisms of retina patterning is limited. We have previously identified the Xenopus Tbx3 gene (XTbx3) which is expressed in the dorsal retina but not in the ventral retina in Xenopus embryos [H. Li, C. Tierney, L. Wen, J. Y. Wu, and Y. Rao (1997) Development 124, 603-615; M.-L. He, L. Wen, C. E. Campbell, J. Y. Wu, and Y. Rao (1999) Proc. Natl. Acad. Sci. USA 96, 10212-10217]. Dosage-sensitive phenotypes in humans suggest that the manipulation of the amount and location of its products could be informative for understanding its normal function. Here we report that ectopic expression of Tbx3 by mRNA injection suppressed formation of the ventral retina. Furthermore, Tbx3 injection led to inhibition of molecular markers for the ventral retina including Pax-2 and netrin, indicating that Tbx3 plays an important role in retina dorsal/ventral patterning in vertebrates by inhibition of gene expression for ventral retina specification.

Animals↗
PubMed1999

Animal-vegetal asymmetries influence the earliest steps in retina fate commitment in Xenopus.

An individual retina descends from a restricted and invariant group of nine animal blastomeres at the 32-cell stage. We tested which molecular signaling pathways are responsible for the competence of animal blastomeres to contribute to the retina. Inactivation of activin/Vg1 or fibroblast growth factor (FGF) signaling by expression of dominant-negative receptors does not prevent an animal blastomere from contributing to the retina. However, increasing bone morphogenetic protein (BMP) signaling in the retina-producing blastomeres significantly reduces their contribution. Conversely, reducing BMP signaling by expression of a dominant-negative BMP receptor or Noggin allows other animal blastomeres to contribute to the retina. Thus, the initial step in the retinal lineage is regulated by position within the BMP/Noggin field of epidermal versus neural induction. Vegetal tier blastomeres, in contrast, cannot contribute to the retina even when given access to the appropriate position and signaling fields by transplantation to the dorsal animal pole. We tested whether expression of molecules within the mesoderm inducing (activin, FGF), mesoderm-modifying (Wnt), or neural-inducing (BMP, Noggin) pathways impart a retinal fate on vegetal cell descendants. None of these, several of which induce secondary head structures, caused vegetal cells to contribute to retina. This was true even if the injected blastomeres were transplanted to the dorsal animal pole. Two pathways that specifically induce head tissues also were investigated. The simultaneous blockade of Wnt and BMP signaling, which results in the formation of a complete secondary axis with head and eyes, did not cause the vegetal clone to give rise to retina. However, Cerberus, a secreted protein that also induces an ectopic head with eyes, redirected vegetal progeny into the retina. These experiments indicate that vegetal blastomere incompetence to express a retinal fate is not due to a lack of components of known signaling pathways, but relies on a specific pathway of head induction.

Activins↗
PubMed1997

Mechanical injury increases bFGF and CNTF mRNA expression in the mouse retina.

We characterized the survival-factor response of the normal mouse retina to mechanical injury by examining the expression of mRNAs for basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), and their receptors, FGF receptor-1 (FGFR-1) and CNTF receptor alpha (CNTFR-alpha). The retina was injured by making an incision through the choroid and retinal pigment epithelium that penetrated the subretinal space of each eye of an adult BALB/c mouse. Retinas were taken 6 hr, 12 hr, 1, 2, 4, 7, 10 and 16 days post-injury. Control animals were without injury. Northern blot analysis was performed to determine bFGF, CNTF and their receptor mRNA levels. A significant increase in bFGF and CNTF mRNAs was observed after injury, along with an increase in glial fibrillary acidic protein (GFAP) expression. More than 2-fold of upregulation of bFGF mRNA was seen as early as 6 hr after injury. This increase reached a maximum of more than 5-fold at day 2 post-injury and then declined slowly, and was still about 2.5-fold of the control level by day 16. Expression of CNTF showed a small increase of about 1.6-fold at 6 hr after injury. The upregulation reached a peak level of about 2.7-fold at day 4 after injury, then declined to control level by day 16. There was only a very small increase in FGFR-1 at 6, 12 and 24 hr after injury, and no significant increases in FGFR-1 at time points longer than 1 day post-injury. Expression of GFAP followed a time course similar to that of bFGF. We conclude that mechanical injury induces bFGF, CNTF, and GFAP expression in the mouse retina with time courses similar to the upregulation of these molecules in rat retina. Compared to the upregulation in rat retina, however, the injury-induced upregulation of bFGF and GFAP is much less in the mouse retina. In addition, there was only a very small induction of FGFR-1 expression in the mouse retina. These findings may explain, at least in part, the lack of injury-induced photoreceptor protection in the mouse retina.

Animals↗