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T van Veen

Publications and source records attributed to T van Veen.

At least 19 recordsLinked to original sources

Reversed ratio of color-specific cones in rabbit retinal cell transplants.

Recently, we have reported on the emergence of various retinal cell types in embryonic rabbit retina transplanted to adult rabbits. When comparing the relative numbers of the spectrally different cone types in the transplants to those in the host or age-matched control retinas, a surprising shift was observed. While in the normal rabbit retina the middle-wavelength-sensitive (M) cones are considerably more abundant than the short-wave-sensitive (S) cones, the S/M cone ratio was found to be the opposite in the graft. The number of rosettes containing only S-cones in high density was found to be considerably higher than that of M-cone rich rosettes. The number of S-cones also exceeded that of the M-cones in each rosette that contained both cell types. Our results were obtained from the systematic immunocytochemical analysis of 15 different transplants derived from transplantations of embryonic rabbit retinas into adult hosts of the same species. The emergence and proportion of the two cone types were followed between 14 and 63 days after transplantation (between 29 and 78 postconceptional days of the donor tissue). Sections from various parts of the transplants were reacted with the monoclonal antibodies COS-1 and OS-2, specific for the middle- and short-wavelength-sensitive cones, respectively. The explanation for the reverse cone ratio in these transplants is not known yet, however, the observed phenomenon may indicate differences between the specification of the two basic cone types.

Animals

Different patterns of retinal cone topography in two genera of rodents, Mus and Apodemus.

Recently, we have reported the peculiar topographic separation of shortwave- and middlewave-sensitive (S and M) cones in the retina of the common house mouse (Mus musculus) and in a number of inbred laboratory mouse strains derived from the same species. In an attempt to follow the phylogeny of the complementary cone fields, we have investigated the retina of other mouse-like rodents. Two monoclonal anti-visual pigment antibodies, OS-2 and COS-1, specific to the S and M cones, respectively, have been used to identify the two cone types. Immunocytochemistry on retinal sections and on whole-mount preparations have shown that, as in the house mouse, the two cone types in the mound builder mouse (Mus spicilegus) occupy opposite halves of the retina. In contrast, in the wood mouse (Apodemus sylvaticus), both cone types are scattered uniformly across the whole retinal surface. Another distinguishing feature between the two genera is the frequency of the S cones. Whereas their density in the Mus species is above 7,000/mm2 in the S-field, the maximum density of the S cones in A. sylvaticus is one order of magnitude smaller. In another species of this genus (the herb field mouse, A. microps), the S cones are completely missing.

Animals

An early decrease in interphotoreceptor retinoid-binding protein gene expression in Abyssinian cats homozygous for hereditary rod-cone degeneration.

Levels of interphotoreceptor retinoid-binding protein (IRBP) protein and message in retinas of Abyssinian cats homozygous for progressive rod-cone degeneration were determined at early ages, well before the onset of clinical retinal degeneration. IRBP gene expression was assessed by immunochemical quantitation of IRBP protein, and by Northern blotting and slot-blotting of total RNA using a human IRBP cDNA probe. Morphology was assessed by electron microscopy and immunocytochemistry. Levels of both IRBP protein and message in affected Abyssinian cat retinas were significantly reduced below normal as early as 4 weeks of age at the earliest stage of retinal disorientation. Opsin mRNA was more abundant in affected Abyssinian cat retinas than in control retinas. This was at least 1 year before the onset of clinical symptoms. The reduction in IRBP gene expression to levels significantly below normal well before the onset of retinal degeneration in affected Abyssinian cat retinas indicates that this represents a primary defect or at least an early problem that could itself cause adverse effects.

Animals

Two different visual pigments in one retinal cone cell.

The retina of the mouse, rabbit, and guinea pig is divided into a superior area dominated by green-sensitive (M) cones and an inferior area in which cones possess practically only short wavelength-sensitive (S) photopigments. The present study shows that the transitional zone between these retinal areas is populated by cones labeled by both the M and S cone photopigment-specific antibodies COS-1 and OS-2. It is concluded that the overwhelming majority of the transitional cones express both visual pigments. A small population of the transitional cones was strongly labeled exclusively by OS-2 (genuine S cones). The results indicate that, in contrast to the generally accepted idea of one visual pigment per one cone cell, cones of certain mammalian species can express different opsins simultaneously under natural conditions. We speculate that the coexpression may be due to the overlapping of regulatory factors determining the M and S fields.

Animals

Myofibrillar Ca2+ sensitization predominantly enhances function and mechanical efficiency of stunned myocardium.

BACKGROUND: Myocardial stunning is characterized not only by a decreased regional postischemic function but also by a relatively high oxygen consumption (ie, decreased mechanical efficiency). Several lines of evidence suggest that the underlying mechanism may involve a decreased sensitivity of the myofibrils to calcium, but in vivo evidence is lacking. We therefore evaluated this hypothesis in vivo using EMD 60263, a calcium-sensitizing agent, which is devoid of any phosphodiesterase-inhibiting properties. METHODS AND RESULTS: We first established the effect of two consecutive doses of EMD 60263 (0.75 and 1.5 mg/kg i.v., n = 7), administered at 15-minute intervals, on segment length shortening (SLS), external work index (EW; the area inside the left ventricular pressure-segment length loop), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) in anesthetized pigs with normal myocardium. After the highest dose of EMD 60263, SLS in the distribution area of the left anterior descending coronary artery (LADCA) increased from 13 +/- 1% at baseline to 17 +/- 1% (P < .05). However, EW, MVO2, and EW/MVO2 were not significantly affected (123 +/- 10%, 98 +/- 9%, and 85 +/- 13% of baseline, respectively). In 14 other anesthetized pigs, myocardial stunning was induced by two sequences of 10 minutes of LADCA occlusion and 30 minutes of myocardial reperfusion. After induction of stunning, the two doses of EMD 60263 (n = 7) or saline (3 and 6 mL, n = 7) were infused. In the distribution area of the LADCA, the stunning protocol caused decreases in SLS from 16 +/- 1% to 8 +/- 1% (P < .05) and in EW to 49 +/- 5% of baseline (P < .05), whereas MVO2 was only minimally affected (P > .05). Consequently, mechanical efficiency decreased to 59 +/- 8% of baseline (P < .05). Saline infusion did not affect any of these regional myocardial variables, but after administration of EMD 60263 SLS recovered dose-dependently to 15 +/- 2% after the highest dose of the drug. EW and mechanical efficiency also recovered dose-dependently to 89 +/- 4% (P < .05 versus stunning) and to 88 +/- 7% (NS versus baseline) of baseline, respectively. In the not-stunned segment, SLS increased from 15 +/- 2% (at baseline) to 18 +/- 2% (after the highest dose), and EW per beat was not changed significantly. An adrenergic mode of action of EMD 60263 was excluded by blocking the alpha- and beta-adrenergic receptors with phentolamine and propranolol, respectively, 15 minutes before administration of EMD 60263 (ie, 15 minutes into the second reperfusion period) in five additional experiments. In these experiments the EMD 60263-induced increases in SLS and EW were not attenuated. Because EMD 60263 decreased heart rate from 106 +/- 4 to 76 +/- 3 beats per minute (P < .05) in the animals with stunned myocardium, we performed five experiments with the specific negative chronotropic compound zatebradine (UL-FS 49, 0.1 to 0.5 mg/kg) to rule out bradycardia as a factor contributing to the effects of EMD 60263. These zatebradine doses lowered heart rate from 116 +/- 5 to 55 +/- 1 beats per minute (P < .05) but had no effect on SLS of stunned and not-stunned myocardium. CONCLUSIONS: Calcium sensitization affects function and mechanical efficiency of stunned myocardium more profoundly than of not-stunned myocardium, lending support to the hypothesis that Ca2+ desensitization of the myofibrils is involved in myocardial stunning.

Animals

Expression of phototransduction cascade genes in the ground squirrel retina.

PURPOSE: This study describes the expression and distribution of phototransduction cascade gene products in the cone-dominant retina of the ground squirrel Spermophilus tridecemlineatus. METHODS: Messenger RNA expression was studied by blot hybridization, and the distribution of the gene products was investigated by immunocytochemistry. RESULTS: RNA blot hybridization showed messages for the alpha 2, beta 1, and beta 3 subunits of transducin but was negative for rhodopsin, alpha 1-transducin, and the alpha, beta, and gamma subunits of cyclic guanosine monophosphate (cGMP) phosphodiesterase. Immunocytochemical labeling indicated that the approximate ratio of the photoreceptor types in ground squirrel retina is 90.6% for green cones, 6.3% for rod-like cells, and 3.1% for blue cones. Rod-like cells were immunopositive for rhodopsin and blue opsin. All photoreceptor elements were labeled by antibodies against alpha 1-transducin (which recognizes both the alpha 1 and alpha 2 isoforms), beta 3-transducin, and the rod gamma subunit of phosphodiesterase, whereas no cells were labeled by antibodies against the rod alpha and beta subunits of phosphodiesterase or against the rod cGMP-gated cation channel. Rod-like cells and blue cones were stained by antibodies against beta 1-transducin. CONCLUSIONS: The authors demonstrate new cone-like traits in the biochemical make-up of rod-like cells, and a distribution of the transducin beta subunit in the ground squirrel is different from that found in other mammals.

Animals

Selective development of one cone photoreceptor type in retinal organ culture.

PURPOSE: The authors have established an organ culture method in which the the postnatal development and the structural integrity of the mouse retina can be maintained for at least 6 weeks. Additionally, they have examined the emergence and in vitro morphogenesis of the photoreceptors and the development of insoluble components of the interphotoreceptor matrix. METHODS: Neural retinas and retinal pigment epithelia from 48-hour-old C3H ++/++ mice were cultured. At various ages, the tissues were fixed and cryosectioned or wholemounted. Photoreceptor development was studied by immunocytochemistry with visual pigment antibodies and by lectin cytochemistry. The ultrastructure of the photoreceptors was studied by electron microscopy. RESULTS: Immunopositive rods and short-wave sensitive cones were detectable as early as 3 days after explantation. From this time on, matrix domains around cones were also identifiable and labelled with peanut agglutinin lectin. However, the antibody specific to the middle-wave sensitive cone pigment failed to recognize any cones throughout the 6-week culture period. CONCLUSIONS: Both basic photoreceptor types appeared and developed in this organ culture system according to a timetable comparable to normal in vivo development. Surprisingly, under these circumstances, one of the two cone pigments was not expressed by any photoreceptors.

Animals

Expression of soluble phototransduction-associated proteins in ground squirrel retina.

PURPOSE: This study describes the expression and distribution of arrestin, phosducin, and recoverin in the cone-dominant retina of the ground squirrel Spermophilus tridecemlineatus. METHODS: mRNA expression was studied by blot hybridization of ground squirrel retinal RNA, with human and murine RNA as controls. The distribution of the gene products in the ground squirrel retina was investigated by immunocytochemistry using radial and consecutive tangential sections. RESULTS: Northern blot hybridization showed messages for arrestin (1.9 kb), phosducin (1.4 kb), and recoverin (1.2 kb) in ground squirrel retinal RNA. Both controls showed transcripts of the same or similar sizes. Rod-like cells and blue cones were stained by antibodies against arrestin and phosducin. The arrestin antiserum stained the whole cell bodies, most intensely in the myoid region, whereas phosducin immunoreactivity was confined to the outer and inner segments, which were stained with approximately equal intensity. The strongest immunoreaction was found in the photoreceptor plasma membrane. Recoverin antibodies recognized the entire soma of all photoreceptor cells. The myoid region and the synaptic pedicles were most heavily stained. No light-dependent migration was observed with either antiserum in any photoreceptor type. CONCLUSION: The presence of arrestin immunoreactivity in rod-like cells and blue cones is consistent with previous reports on other mammals. However, it has not been reported previously that phosducin immunoreactivity is distributed in the same way. The colocalization of arrestin and phosducin in rod-like cells and blue cones is yet another trait distinguishing blue cones from red and green cones.

Animals

Complementary cone fields of the rabbit retina.

PURPOSE: Complementary cone fields have been considered a unique feature of the mouse retina. In an attempt to map the arrangement of the color-specific cones in other mammals, the authors investigated the rabbit, a commonly used experimental animal for vision research. METHODS: For the identification of the different cone types immunocytochemistry was used with two monoclonal antibodies, each specific to the middle- to long-wave (red-green) and short-wave (blue) sensitive visual pigments, respectively. RESULTS: The major part of the retinal surface, including the visual streak, exhibited a dominance of M (middle-wave sensitive) cones (6 to 13,000/mm2) versus S (short-wave sensitive) cones (1 to 2,500/mm2). In contrast, the lower 5% to 6% of the total retinal area showed a complete lack of green cones and a high density of blue cones (11,000/mm2). The authors designate this crescent-like area the blue streak of the rabbit retina. CONCLUSION: In addition to the visual streak primarily abundant in green cones, there is a specialized area of the rabbit retina that is densely and exclusively populated with blue cones. Although the relative extension of this peculiar cone field is considerably smaller than the S-field of the mouse retina, its position is similar in that it occupies the lowermost part of the retina. The functional implication of this area is unknown.

Animals

Spatial and temporal differences between the expression of short- and middle-wave sensitive cone pigments in the mouse retina: a developmental study.

In an earlier study we found a topographic separation of middlewave-sensitive (M) and shortwave-sensitive (S) cones in the adult mouse retina. In the present study we investigated the development of the two colour-specific cone types to see whether there is also a temporal difference between the expression of the specific cone visual pigments. Using two anti-cone visual pigment antibodies, COS-1 and OS-2, we compared the densities of immunopositive cone outer segments on retinal whole mounts derived from mice of various ages. The first detectable cone outer segments were the S-cones which appeared in the inferior half of the retina on postnatal day 4. At this stage, the density of the S-cones was very low (30-40 cones/retina) but increased steadily on the following days to reach a value comparable to that of adults by P30 (18,000/mm2). This cone type always remained much more abundant in the lower part of the retina throughout the whole retinal development. In the superior half of the retina, a few S-cones appeared from postnatal day 7; however, their number always remained about one order of magnitude lower than in the inferior part. In contrast, M-cone outer segments were not identifiable earlier than postnatal day 11 and were confined exclusively to the superior part of the retina during the whole developmental process. On postnatal day 12, their density was 1,900/mm2 and increased to a value of 11,000/mm2 by postnatal day 30, which represented the adult stage. As shown by comparison of isodensity lines derived from immunocytochemical reactions of whole mount retinas, the two cone types occupied complementary halves of the mouse retina with maximum density centres located in opposite retinal quadrants. We conclude that 1) in contrast to the primate retina, mouse S-cones precede the M-cones in their development, and 2) the spatial arrangements of the two cone types is maintained throughout the whole differentiation process.

Animals

Hyperplastic neuroretinopathy and disorder of pigment epithelial cells precede accelerated retinal degeneration in the SJL/N mouse.

We have found a complex eye disease in the SJL/N mouse. This animal is closely related to the SJL/J mouse, which is homozygous for retinal degeneration (rd) and which also suffers from extraocular reticulum cell sarcomas at around 200 days of age. In the SJL/N animal, a high incidence of subretinal tumor is present at 9 days after birth. Furthermore, we have observed an extensive neuroretinal hyperplasia, a phenomenon that is termed "hyperplastic neuroretinopathy", and that is probably the consequence of elevated levels of cytokines in the animals. In addition to these anomalies, the SJL/N mouse shows progressive dystrophy of the retinal pigment epithelium (RPE) from day 4 onwards, and accelerated photoreceptor cell degeneration is completed by day 16. The early RPE dystrophy appears to be a secondary autoimmune disease, since cells in this structure and in the choroid develop MHC class II antigens, whereas we suspect that the accelerated photoreceptor cell loss is induced by a soluble toxic agent. The F1 progeny derived from cross-breeding the SJL/N and Balb/c +/+ strains also shows a high incidence of subretinal tumor and hyperplastic neuroretinopathy, but neither the RPE dystrophy nor retinal degeneration.

Age Factors

Diethylene glycol distearate (DGD): a versatile embedding medium for retinal cytochemistry.

Embedment in diethylene glycol distearate (DGD) was shown to be highly desirable and versatile for retinal cytochemical studies, including in situ hybridization, immuno- and lectin cytochemistry. This method allows for preservation of fine tissue detail as well as good reaction sensitivity. It appears to be more suitable than most other methods currently used for light microscopic retinal cytochemistry.

Animals

Photoreceptor-specific protein expression of mouse retina in organ culture and retardation of rd degeneration in vitro by a combination of basic fibroblast and nerve growth factors.

Previously we have presented the morphological features of a neonatal mouse retinal explant kept in culture for 3 to 4 weeks. To further evaluate the organotypic parameters of the tissue we have examined the presence of opsin, S-antigen, and interphotoreceptor retinoid-binding protein (IRBP) in the same experimental paradigm, using light microscopic immunocytochemistry. In vitro, opsin and S-antigen staining is found in photoreceptor somata from genetically normal explants and those derived from mice with the rd or the rds mutation. When present, inner and outer segments label more intensely. No IRBP staining has been found in cell bodies of any genotype. However, some labeling is found in the plexiform layers and in the inner segments. The results indicate that photoreceptor proteins are continuously produced in vitro. This further establishes the organotypic nature of the retinal explant in culture. The administration of growth factors to these explants has been investigated. Neither basic fibroblast growth factor nor nerve growth factor alone has affected the explants phenotype. However, the combination of these proteins has significantly retarded rd cell loss in vitro.

Animals

Difference in PNA label intensity between short- and middle-wavelength sensitive cones in the ground squirrel retina.

PURPOSE: Peanut agglutinin lectin (PNA) is known for its selective binding to cone cells and to the cone domains of the interphotoreceptor matrix. In the current study, the authors investigated whether there is any difference in PNA binding between color-specific cones of the cone-dominant ground squirrel. METHODS: Consecutive serial sections of the retina of Spermophilus tridecemlineatus were reacted alternately with PNA and antivisual pigment antibodies. The PNA labels associated with short- and middle-wavelength-sensitive cones (S-cones and M-cones, respectively) were compared with fluorescent lectin cytochemistry. RESULTS: Although all rod-like cells were left unstained, the cones exhibited a specific lectin label. There was, however, a significant difference between the two cone types; the intensity of the ring-like PNA label in the matrix sheath around S-cones significantly exceeded that of the M-cones. CONCLUSIONS: The difference in PNA label intensity indicates a difference in the composition of the matrix sheaths surrounding the two respective cone types. To the authors' knowledge, this is the first report on lectin-cytochemical discrimination of cone matrix sheaths and the first lectin study in the ground squirrel retina leading to the observation that PNA can distinguish the three characteristic photoreceptor types in this animal. In this respect, the rod-like cells of the ground squirrel retina were shown to be no different from rod cells of other species.

Animals

Structural changes of the interphotoreceptor matrix in an inherited retinal degeneration: a lectin cytochemical study of progressive rod-cone degeneration.

PURPOSE: In the retinal disorder progressive rod-cone degeneration (prcd) in miniature poodle dogs, the photoreceptor layer degenerates slowly in the course of 5 to 7 years. Components of the interphotoreceptor matrix form a continuous extracellular lattice around photoreceptors. The purpose was to study the photoreceptor cell-matrix interactions during the disease and degeneration phases. Because degeneration rate was slower in cones, the authors also wanted to investigate whether there was a link between the degeneration and the photoreceptor-specific interphotoreceptor matrix domains. METHODS: Rod- and cone-specific interphotoreceptor matrix domains were examined during two periods: before morphological signs of disease had appeared and during the degenerative stages. Two lectin probes were used; wheat germ agglutinin and peanut agglutinin. By their affinity for terminal carbohydrates, the lectins visually separated the two photoreceptor-specific domains and allowed follow-up of the fate of the rod and cone matrices separately. RESULTS: Before and during the course of disease, the lectin distribution in rod and cone domains remained normal, however, in the degenerative phase of the disease, there were structural changes in the matrix domains. The matrix connections between the individual domains was disrupted and single domains were formed. Cone domains and, to a lesser degree rod domains, were thickened around the inner and outer segments. CONCLUSIONS: The changes occurring in the photoreceptor-specific domains were indicative of structural adaptation to cell death and to degenerative conditions. There was no evidence of an active involvement of the interphotoreceptor matrix components studied in the disease process.

Animals

Rod and cone specific domains in the interphotoreceptor matrix.

The insoluble matrix domain of the interphotoreceptor matrix (IPM) from normal dog, cat, and mouse retinae were characterized using lectin cytochemistry. The lectins WGA (wheat germ agglutinin) and PNA (peanut agglutinin) were used to label interphotoreceptor matrix microdomains in cryosections of retinal tissue and in extracted insoluble matrix. Retinal cryosections and extracted matrix were examined by epifluorescence microscopy and scanning confocal laser microscopy, the latter allowed for the removal of all background fluorescence and gave increased resolution. The insoluble matrix was extracted as a continuous sheet that was comprised of two photoreceptor-specific matrix domains distinguished both by the size of the domains, and by differential binding of WGA and PNA lectins. Each domain encloses a photoreceptor inner and outer segment. Individual rod-associated domains were connected into a hexagonal lattice and this pattern was regularly interrupted by the larger cone-associated domains which have 8-10 surrounding rod domains. The PNA lectin primarily labeled the cone-associated matrix with faint binding to the rod matrix; the WGA lectin labeled both the rod- and cone-associated matrix.

Animals

Photoreceptor degeneration and loss of immunoreactive GABA in the Abyssinian cat retina.

GABA (gamma-amino butyric acid) and its synthesizing enzyme, GAD (glutamate decarboxylase; EC 4.1.1.15) were localized in the retina of Abyssinian cats homozygous for a recessively inherited retinal degenerative disorder which in several respects is similar to the human disease, retinitis pigmentosa. Clinically normal mongrel cats and heterozygous Abyssinian cats were studied for comparison. The GABA and GAD immunoreactive neurons of the heterozygous or young homozygous (clinically unaffected animals) had the same distribution and morphology as normal mongrel European type cats. The neuronal GABA immunoreactivity in both the inner and outer parts of the retina gradually disappeared in the course of the disease, with little or no loss of GAD immunoreactive neurons. Early in the disease, the changes were most severe in patches in the mid periphery of the eye and then spread both centrally and peripherally. Loss of photoreceptors was a prerequisite for the loss of GABA immunoreactivity. The observations show that retinal changes are not limited to the photoreceptors. The GABA loss is not likely to be due to a loss of neurons, because of the persistence of GAD immunoreactive neurons.

Animal Husbandry