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At least 595 records · Page 33Linked to original sources
PubMed2003

Somatostatin inhibits potassium-evoked glutamate release by activation of the sst(2) somatostatin receptor in the mouse retina.

In the mammalian retina, somatostatin (SRIF-14) acts through distinct receptor subtypes (sst(1-5)). Among them, sst(2) has been localized to numerous retinal cells, including photoreceptors and rod bipolar cells (RBCs). The specific role of sst(2) in the retina is largely undetermined. In this study, we characterized retinas of mice with targeted deletion of sst(2) (sst(2) KO) and we investigated functions of sst(2) in respect to its possible modulation of glutamate (GLU) release, as measured by HPLC. In contrast with wild-type (WT) mice, sst(2) mRNA and sst(2A) immunoreactivity were no longer detectable in the retina of sst(2) KO mice. In retinal explants of WT mice, SRIF and its analogue octreotide that displays high selectivity for sst(2), similarly reduced the evoked release of GLU without affecting its basal level. In sst(2) KO retinas, SRIF or octreotide did not affect GLU release indicating that they act at sst(2). Unexpectedly, the compound CYN-154806, although introduced as the first potent sst(2) antagonist, reduced the evoked release of GLU with equipotency to SRIF and octreotide. Its inhibitory effect was no longer observed in sst(2) KO retinas, indicating that this substance acts at sst(2) receptors as an agonist. In conclusion, SRIF controls evoked release of GLU through sst(2) receptors and this control may represent part of a mechanism by which SRIF regulates GLU concentration in the retina.

Animals↗
PubMed2003

Benzodiazepine and kainate receptor binding sites in the RCS rat retina.

BACKGROUND: The effect of age and photoreceptor degeneration on the kainate subtype of glutamate receptors and on the benzodiazepine-sensitive gamma-aminobutyric acid-A receptors (GABA(A)) in normal and RCS (Royal College of Surgeons) rats were investigated. METHODS: [(3)H]Kainate and [(3)H]flunitrazepam were used as radioligands for kainate and GABA(A)/benzodiazepine()receptors, respectively, using the quantitative receptor autoradiography technique. RESULTS: In both normal and RCS rat retina we observed that [(3)Eta]flunitrazepam and [(3)Eta]kainate binding levels were several times higher in inner plexiform layer (IPL) than in outer plexiform layer (OPL) at all four ages studied (P17, P35, P60 and P180). Age-related changes in receptor binding were observed in normal rat retina: [(3)Eta]flunitrazepam binding showed a significant decrease of 25% between P17 and P60 in IPL,and [(3)Eta]kainate binding showed significant decreases between P17 and P35 in both synaptic layers (71% in IPL and 63% in OPL). Degeneration-related changes in benzodiazepine and kainate receptor binding were observed in RCS rat retina. In IPL, [(3)Eta]flunitrazepam and [(3)Eta]kainate binding levels were higher than in normal retina at P35 (by 24% and 86%, respectively). In OPL, [(3)Eta]flunitrazepam binding was higher in RCS than in normal retina on P35 (74%) and also on P60 (62%). CONCLUSIONS: The results indicate that postnatal changes occur in kainate and benzodiazepine receptor binding sites in OPL and IPL of the rat retina up to 6 months of age. The data also suggest that the receptor binding changes observed in the RCS retina could be a consequence of the primary photoreceptor degeneration.

Animals↗
PubMed2006

Subthreshold transpupillary thermotherapy of the retina and experimental choroidal neovascularization in a rat model.

PURPOSE: To study the effect of subthreshold transpupillary thermotherapy (TTT) on the retina and experimental choroidal neovascularization (CNV) in the rat. METHODS: Subthreshold TTT was performed on normal Brown Norway rats or those with krypton laser-induced CNV and appropriate controls with an 810-nm diode laser coupled to a slit lamp. At different intervals after TTT, fundus fluorescence angiography (FFA) and histopathological examinations were performed. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was used to detect apoptosis. Immunohistochemistry was used to detect heat shock protein 70 (Hsp70) expression. RESULTS: In normal retina, edema and whitening was found on day 1 after TTT. Different degrees of hyperfluorescence could be seen on FFA. Obvious retina damage, especially in the outer layers, was observed by histology in all the lesions that appeared whitened. In the CNV there was congestion and less damage in the overlying retina than in normal retina on day 1 after TTT. Apoptosis was detected in all retinal layers and CNV lesions by TUNEL. In normal eyes, after TTT, Hsp70 expression was increased in the inner layers of the retina and some of the cells in the choroid. Hsp70 was also increased in laser-induced CNV. Two weeks after TTT, the CNV showed a tendency for fibrosis by Masson staining. FFA did not show much change in the CNV lesions 2 weeks after TTT. CONCLUSION: Subthreshold TTT has adverse effects on the overlying retina and thus is likely to cause significant functional and morphological long-term sequelae. Subthreshold TTT can cause apoptosis in laser-induced CNV in rats.

Animals↗
PubMed2001

Retina-sparing laser treatment of occult CNV by vitrectomy and localised detachment of the macula.

BACKGROUND: Occult choroidal neovascularisation (CNV) was treated by a novel surgical approach. In order to spare the retina during laser photocoagulation of occult CNV, the retina was detached by subretinal infusion of a ringer solution. After localised detachment of the neural retina the CNV was transretinally coagulated by an endoprobe of a diode laser. METHODS: Twelve patients with occult CNV were treated in such a way. The mean duration of follow-up was 3.5 +/- 1.6 months. After 4 weeks fluorescein angiography and indocyanine green angiography were performed in all patients. Laser exposure time was 1.1 +/- 0.7 s and laser energy was 1.2 +/- 0.7 W. RESULTS: In 10 of 12 patients the retina could be successfully detached and performed. In all cases the retina remained unchanged during laser photocoagulation. After 5 days subtle RPE atrophy and after 1 month obvious RPE atrophy was found. After 4 weeks, in 8 of 10 cases the CNV was completely occluded and no late leakage was found. Three months after operation, retinal atrophy could be seen in all cases. Visual acuity was lower in 6 and unchanged in 4 of 10 patients. CONCLUSION: Despite acute sparing of the neural retina the long-term effects are not better than after conventional laser photocoagulation, because secondary atrophy of the retina develops.

Aged↗
PubMed2005

Brain-derived neurotrophic factor modulates the dopaminergic network in the rat retina after axotomy.

Dopaminergic cells in the retina express the receptor for brain-derived neurotrophic factor (BDNF), which is the neurotrophic factor that influences the plasticity of synapses in the central nervous system. We sought to determine whether BDNF influences the network of dopaminergic amacrine cells in the axotomized rat retina, by immunocytochemistry with an anti-tyrosine hydroxylase (TH) antiserum. In the control retina, we found two types of TH-immunoreactive amacrine cells, type I and type II, in the inner nuclear layer adjacent to the inner plexiform layer (IPL). The type I amacrine cell varicosities formed ring-like structures in contact with AII amacrine cell somata in stratum 1 of the IPL. In the axotomized retinas, TH-labeled processes formed loose networks of fibers, unlike the dense networks in the control retina, and the ring-like structures were disrupted. In the axotomized retinas treated with BDNF, strong TH-immunoreactive varicosities were present in stratum 1 of the IPL and formed ring-like structures. Our data suggest that BDNF affects the expression of TH immunoreactivity in the axotomized rat retina and may therefore influence the retinal dopaminergic system.

Amacrine Cells↗
PubMed1998

High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance.

Glutamate is the major excitatory neurotransmitter of the mammalian retina and glutamate uptake is essential for normal transmission at glutamatergic synapses. The reverse transcriptase-polymerase chain reaction (RT-PCR) has revealed the presence of three different high-affinity glutamate transporters in the rat retina, viz. GLAST-1, GLT-1 and EAAC-1. No message has been found in the retina for EAAT-4, a transporter recently cloned from human brain. By using membrane vesicle preparations of total rat retina, we show that glutamate uptake in the retina is a high-affinity electrogenic sodium-dependent transport process driven by the transmembrane sodium ion gradient. Autoradiography of intact and dissociated rat retinae indicates that glutamate uptake by Müller glial cells dominates total retinal glutamate transport and that this uptake is strongly influenced by the activity of glutamine synthetase. RT-PCR, immunoblotting and immunohistochemistry have revealed that Müller cells express only GLAST-1. The Km for glutamate of GLAST-1 is 2.1+/-0.4 microM. This study suggests a major role for the Müller cell glutamate transporter GLAST-1 in retinal transmitter clearance. By regulating the extracellular glutamate concentration, the action of GLAST-1 in Müller cells may extend beyond the protection of neurons from excitotoxicity; we suggest a mechanism by which Müller cell glutamate transport might play an active role in shaping the time course of excitatory transmission in the retina.

ATP-Binding Cassette Transporters↗
PubMed2001

Onset and time course of apoptosis in the developing zebrafish retina.

In mammalian development, apoptosis spreads over the retina in consecutive waves and induces a remarkable amount of cell loss. No evidence for such consecutive waves has been revealed in the fish retina so far. As the zebrafish is of growing importance as a model for retinal development and for degenerative retinal diseases, we examined the onset and time course of apoptosis in the developing zebrafish retina and in adult fish. We found that apoptosis peaked in the ganglion cell layer (GCL) and inner nuclear layer (INL) in early developmental stages (3-4 days post-fertilization; dpf) followed by a second, but clearly smaller wave at 6-7dpf. Apoptosis in the outer nuclear layer (ONL) started at 5dpf and peaked at 7dpf. This late-onset high peak of apoptosis of photoreceptors is different from that of all other species examined to date. With 1.09% of cells in the GCL and 1.10% in the ONL being apoptotic, the rate of apoptosis in the developing zebrafish retina was conspicuously lower than that observed in other vertebrates (up to 50% in GCL). During development (2-21dpf), apoptotic waves were most obvious in the central retina, whereas in the periphery near the marginal zone (MZ), apoptosis was much lower; in adult animals, practically no apoptosis was present in the central retina but it still occurred near the MZ. Our data show that the onset and time course of apoptosis in the GCL and INL of the zebrafish is comparable with other vertebrates; however, the amount of apoptosis is clearly reduced. Thus, apoptosis in the zebrafish retina may serve more as a mechanism for the fine tuning of the retinal neuronal network after mitotic waves during development or in remaining mitotic areas than as a mechanism for eliminating large numbers of excess cells.

Animals↗
PubMedDate not supplied

Quantitative analyses of mRNA and protein levels of neurotrophin-3 in the rat retina during postnatal development and aging.

PURPOSE: In this study, we sought to elucidate changes in the levels of neurotrophin-3 (NT-3) in the rat retina throughout postnatal development and aging. METHODS: We demonstrated NT-3 localization in the retina by immunohistochemistry. Protein and mRNA levels of NT-3 were quantified by enzyme-linked immunosorbant assay and semiquantitative reverse transcriptase-polymerase chain reaction, respectively. NT-3 protein levels were assayed in the various regions of the central nervous system. Age-associated changes in protein and mRNA levels of NT-3 in the retinas were assessed. RESULTS: NT-3-immunoreactivity localized in the ganglion cell layer, inner nuclear layer, and outer nuclear layer. NT-3 content in the retina was relatively high in the examined regions of the central nervous system. Retinal NT-3 protein levels decreased after eye opening, whereas mRNA levels were constant. Both mRNA and protein levels of NT-3 in the retinas of aged animals remained constant. CONCLUSIONS: Our observations suggest that NT-3 regulation in the retina is independent of increasing visual stimuli after eye opening. Stable expression of NT-3 in the adult retina suggests a possible role in the maintenance of the retinal environment throughout later life.

Aging↗
PubMedDate not supplied

Contribution of nitric oxide-producing cells in normal and diabetic rat retina.

PURPOSE: To examine the immunohistochemical localization of L-arginine and L-citrulline and determine where and how nitric oxide (NO) is produced in the normal and streptozotocin (STZ)-induced diabetic rat retinas. METHODS: NO is produced when L-arginine is changed to L-citrulline by NO synthase (NOS). In normal and STZ-induced diabetic rats, using an immunohistochemical method, we examined the retinal distribution of L-arginine and L-citrulline after intracardiac perfusion. We studied the distribution of NOS after immersed fixation and analyzed the number of neuronal NOS (nNOS)-positive neurons. RESULTS: We observed L-arginine localization in the internal limiting membrane (ILM), the ganglion cell layer (GCL), and the inner nuclear layer (INL). L-Arginine immunoreactivity in the diabetic rat retinas was found in the inner plexiform layer (IPL), as well as in the normal retina. L-Citrulline immunoreactivity in the normal and diabetic retinas was observed in the ILM, the GCL, the IPL, and the INL. nNOS staining in the normal and diabetic rat retinas was observed in the GCL, the IPL and the INL. The number of nNOS-positive amacrine cells was less in the diabetic rat retinas. CONCLUSION: NO might be produced in the GCL and amacrine cells, which show immunoreactivity to L-arginine, L-citrulline, and nNOS. In the early stage of diabetic retinopathy in STZ rat retinas, diabetes disturbed the function of the nNOS-positive amacrine cells and reduced NO production via nNOS.

Amacrine Cells↗
PubMed1982

Reduction in numbers of large ganglion cells in cat retina following intravitreous injection of antibodies.

Antibodies were prepared against large ganglion cells isolated from bovine retina and injected into the vitreous chamber of 1 eye in 6 adult cats. The other eye of each cat received either a control pre-immune gamma-globulin injection or was untreated. After a survival time of 9-86 days, ganglion cell density was assessed from Nissl-stained retinal whole-mounts. In each cat, there were fewer large ganglion cells (alpha-cells) in the immunoglobulin-injected retina than in the control retina. The reduction in large ganglion cells occurred in patches adjacent to areas of approximately normal large ganglion cell density. Counts of the number of large ganglion cells in both eyes of the 6 cats indicated that the immunoglobulin injected eyes had from 8% to 61% (mean 32%) fewer large ganglion cells than the paired control eyes. This was significantly greater than the difference in the number of large ganglion cells between pairs of normal or control-injected eyes. The magnitude of the effect was not related to the survival time following the immunoglobulin injection. Cell size measures of all ganglion cells in selected areas of retina indicated that the small ganglion cells were unaffected by the antibodies. However, there was a suggestion that the largest of the medium size ganglion cells were affected in addition to the large ganglion cells. Counts of total ganglion cells per unit area in affected regions of retina revealed a reduced overall density, suggesting that the ganglion cells were lost rather than decreased in size. These results indicate that antibodies to the large ganglion cells can be used to reduce the number of large ganglion cells (alpha-cells) in the cat retina. Since these cells correspond to the Y-cell functional class of ganglion cells in the cat retina, the antibodies may provide a useful tool for studying Y-cell function in the visual pathways.

Animals↗
PubMed1987

D1 dopamine receptors in the rat retina: effect of dark adaptation and chronic blockade by SCH 23390.

Chronic administration of SCH 23390 (0.03 mg/kg s.c., three times daily), a selective D1 dopamine (DA) receptor blocker, markedly increased the [3H]SCH 23390 binding in the rat retina. As revealed by the Scatchard plot analysis of saturation data from retinal homogenates, chronic SCH 23390 increased the total number of binding sites by 34% when compared to tissue from solvent-treated rats but failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. The up-regulation of [3H]SCH 23390 binding sites was paralleled by an increase in the sensitivity of retina DA-sensitive adenylate cyclase. In fact, DA (5 X 10(-6) M to 10(-4) M) produced a higher accumulation of cyclic AMP (from 58 to 128%) in the retina of SCH 23390-treated rats as compared to the accumulation (from 35 to 80%) found in tissue from solvent-treated rats. Since dark adaptation decreases dopaminergic function in the rat retina, the influence of environmental lighting on [3H]SCH 23390 binding and DA-sensitive adenylate cyclase activity was studied. After 4 h of dark adaptation the density of [3H]SCH 23390 binding sites was higher (32%) than that from light-adapted rats. On the other hand, dark adaptation failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. Moreover, DA elicited a greater stimulation of adenylate cyclase activity in homogenates of retina from dark-adapted rats. Thus, the maximum adenylate cyclase response to DA resulted higher in the retina of dark-adapted rats (152%) than that found in the retina of light-adapted animals (97%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1990

Desensitization of the dopaminergic system in bovine retina following incubation with high potassium.

The effect of potassium depolarization on dopamine D1 receptor activity in bovine retina was investigated. Preincubation of bovine retinas in buffer containing high KCl (56 mM) as compared to a low KCl control buffer resulted in a significant decrease in dopamine-stimulated adenylate cyclase activity with no change in basal or GTP-stimulated adenylate cyclase activity. The apparent Vmax for dopamine was decreased from 102 +/- 15 pmol/min/mg protein in retinas preincubated in high KCl to 71 +/- 11 pmol/min/mg protein in control retinas (n = 5). The apparent Ka for dopamine stimulation of the enzyme did not change. The potassium-induced desensitization could be blocked by preincubation with the dopamine antagonist cis-flupenthixol suggesting that the desensitization was caused by the release of dopamine. The rapid desensitization was not accompanied by a change in D1 receptor density as assessed by binding of [3H]SCH23390 nor in agonist binding as assessed by competition of the selective D1 agonist, SKF38393, for [3H]SCH23390 binding. The potassium-induced desensitization was mimicked by preincubation of retinas in control medium containing isobutylmethylxanthine or dibutyryl cyclic AMP. Incubation of retinas in 56 mM KCl also led to a decrease in activation of adenylate cyclase by vasoactive intestinal polypeptide. These results strongly suggest that potassium depolarization leads to a very rapid heterologous desensitization of adenylate cyclase in bovine retinas.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Distribution of immunoreactivity to protein kinase C in the turtle retina.

Immunocytochemical staining procedures using the HRP-complexed antibody to protein kinase C (PKC) have been carried out on the turtle retina. Wholemounts and frozen sections of retina have been studied by light microscopy to evaluate PKC immunoreactivity after stimulation of the retina with light and neurotransmitters known to be active in the vertebrate retina. The most dramatically stained sites are cone synaptic pedicles and bipolar cells under all conditions. Ganglion cells stain weakly under certain conditions. Applying the antibody to a 'control' retina under dark adapted conditions results in uniform background staining of both hyperpolarizing and depolarizing bipolar pathways, while stimulating the retina with K+ under dim light conditions results in discretely stained bipolar cells and a prominent band of staining in stratum 4 of the inner plexiform layer. Stronger stimulation of bipolar cells with their terminals contributing to strata 3 and 4 and the continuous dominant band in stratum 4 can be elicited with incubation of the retina in neurotransmitter agonists, GABA and dopamine. Incubation with dopamine, in particular, brings out the putative dopaminergic amacrine cell. The only condition in which a strong band in stratum 2 can be demonstrated is under stimulation with a flashing bar of spot of light. Thus K+ and neurotransmitter stimulation elicit PKC staining in neurons contributing to the ON or depolarizing sublamina of the IPL, while intermittent flashing light stimulus is required to elicit PKC staining in the OFF or hyperpolarizing sublamina of the IPL.

Animals↗
PubMed1990

A new type of wide-field horizontal cell, presumably linked to blue cones, in rabbit retina.

Horizontal cells of vertebrate retina play an important role in the formation of visual receptive field surrounds of bipolar cells, and hence in the centre-surround receptive field organization of retinal ganglion cells. In some retinas, horizontal cells also play a major functional role in the first stage of colour-coding of visual stimuli. We have identified a new type of horizontal cell, called 'type C', in rabbit retina, which unlike type A and type B horizontal cells, contacts only a small fraction of cone photoreceptors, possibly blue cones. The multiple, sparsely branched axons of type C cells are well-positioned to contact bipolar dendrites in a feedforward manner. In summary, we propose (1) that the presence in rabbit retina of 3 types of cone horizontal cell, A, B, and C, may represent a more common pattern in mammalian retinae, shared with many non-mammalian retinas which contain colour-coded neurons, (2) that type C cells connect principally to blue cones, and (3) that type C cells are more common in retinas, such as those of squirrels, and to a lesser extent rabbits, in which blue cones play a major role in the colour coding of visual signals.

Animals↗
PubMed1992

Effects of lesions of the optic nerve, optic tectum and nervus terminalis on rod precursor proliferation in the goldfish retina.

Teleost retinas grow throughout life by proliferation of neuroblasts at the retinal margin and dedicated rod precursors in the outer nuclear layer. Mechanisms regulating this proliferation are largely unknown. Previous investigators observed that rod precursor replication, as detected by incorporation of radioactive thymidine into cells of the outer nuclear layer, is enhanced after optic nerve crush. We attempted to determine whether this was due to severing of the retinopetal (nervus terminalis, n.t.) or retinofugal (retinal ganglion cell) axons in the optic nerve of the goldfish, Carassius auratus. In the first series of experiments, we ablated unilaterally the optic nerve, olfactory bulb (containing n.t. ganglia), or optic tectum (containing retinal ganglion cell axons and n.t. collaterals). Rod precursor proliferation increased dramatically in both retinas as soon as 5 days after surgery; in addition, the numbers of dividing cells were greater in the ipsilateral retina 10-15 days after optic nerve crush or tectal ablation and in the contralateral retina 20-25 days after olfactory bulb ablation. These observations are not accounted for by the known projections of retinal ganglion cells, but are consistent with the projections of the n.t. In the second series of experiments, n.t. projections to the brain and retina were severed bilaterally 7-8 weeks before the unilateral optic nerve crush or hemitectal ablation. Rod precursor proliferation increased as before, but the quantities of dividing cells were always equal in both retinas. We conclude that the n.t. may modulate rod proliferation locally and that injury to (some) brain regions may cause release of mitogens that affect rod precursors in both retinas.

Animals↗
PubMed1993

Distribution of parvalbumin immunoreactivity in the vertebrate retina.

Parvalbumin, a calcium-binding protein thought to buffer intracellular calcium, is expressed in selected neuronal and non-neuronal cell populations. We used a well-characterized antibody directed against parvalbumin to investigate the distribution of parvalbumin in the retina of twelve vertebrate species to evaluate patterns of cellular expression for recurrent functional features. Parvalbumin immunoreactivity was displayed by subpopulations of ganglion, amacrine, bipolar and horizontal cells in different species-specific combinations. In the pigeon retina, subpopulations of amacrine, ganglion and bipolar cells were immunoreactive for parvalbumin. Parvalbumin immunoreactive bipolar cells in this species were mostly confined to the temporal dorsal region of the retina. In the owl, no immunoreactive amacrine cells were found, but many bipolar cells displayed parvalbumin immunoreactivity. In the teleost retina, amacrine and ganglion cells were found to be immunoreactive for parvalbumin. A high degree of species-specific variation was encountered in the mammalian retina. The most consistent finding within this class was that subpopulations of parvalbumin-immunoreactive amacrine cells were consistently observed in every species. In the rabbit, horizontal and ganglion cells displaying parvalbumin immunoreactivity were also seen. In rodents (hamster, ground squirrel), parvalbumin immunoreactivity was displayed by subpopulations of amacrine cells and, in the squirrel, by some ganglion cells as well. In the cat and in the baboon retina, parvalbumin immunoreactivity was found in horizontal cells, ganglion cells and a subpopulation of amacrine cells. The distribution of parvalbumin immunoreactive neurons in the vertebrate retinae studied showed no systematic correlation with phylogenetic proximity. The expression of parvalbumin within the systems of retinal neurons may therefore reflect the functional needs of different visual behaviors.

Animals↗
PubMed1996

Circadian regulation of hydroxyindole-O-methyltransferase mRNA levels in rat pineal and retina.

Hydroxyindole-O-methyltransferase (HIOMT, EC 2.1.1.4) catalyzes the methylation of acetylserotonin to complete the synthesis of melatonin in the pineal and retina. A complete 1728 nucleotide cDNA encoding rat pineal HIOMT was isolated, characterized, and used to evaluate day/night levels of HIOMT mRNA. As previously reported for HIOMT enzyme activity, HIOMT mRNA levels were also greater in the pineal than in the retina. Northern blot analysis and in situ hybridization were useful for detection of HIOMT mRNA in the pineal but not the retina, whereas the reverse transcriptase-polymerase chain reaction or RNase protection assay revealed transcripts for HIOMT both in the pineal and retina. Investigating HIOMT mRNA levels in rat pineal and retina at 6 time-points throughout a 24 h period revealed higher levels of HIOMT message during darkness. The daily fluctuation in HIOMT mRNA persisted in constant darkness, verifying an endogenous circadian rhythm both in the pineal and retina. In mammalian pineals, sympathetic innervation, synthesizing norepinephrine that activates beta (beta) adrenergic receptors, entrain several circadian bodily functions through the synthesis and release of melatonin. A single injection of the beta-adrenergic agonist, isoproterenol, induced a dramatic increase of HIOMT mRNA levels in the light-adapted pineal, in vivo. Moreover, a single injection of the beta-adrenergic antagonist, propranolol, prevented the nocturnal increase of pineal HIOMT mRNA. Using a combination of methods, it has been shown that the level of HIOMT mRNA fluctuates daily in both the pineal gland and retina. This day/night rhythm can be modulated either by beta receptor agonists or antagonists when applied appropriately during the circadian cycle, suggesting that the mRNA changes in HIOMT may be controlled at the transcriptional level.

Acetylserotonin O-Methyltransferase↗
PubMed1986

Axonal pathfinding in organ-cultured embryonic avian retinae.

Eye cups from stage 14-28 (E2 to E5) chick and quail embryos consisting of neural retina, lens, and vitreous body were cultured for 1 or 2 days. These eyes expanded by proliferation of the retinal cells and the surface areas of the retinae increased several-fold. The area covered by ganglion cells and axons also expanded in vitro. [3H]Thymidine labeling showed extensive proliferation of the neuroepithelial cells including the formation of new ganglion cells. Culturing eyes from embryos before stage 17 results, as in vivo, in the generation of the first ganglion cells of the retina, but unlike in the in vivo situation, the outgrowing axons always formed a random fiber net in the central portion of the retina. A defined axonal pattern identical to the in vivo developed only in specimens from embryos of stage 17 and older. Some aberrant axons, however, were also observed at the retinal periphery in specimens from embryos of more advanced stages (20-24), but only during the second day of culturing. Axons in retinae from embryos of stages 23 to 26 heading toward the optic fissure often crossed the fissure and, in contrast to the situation in vivo, invaded the opposite retinal side. These axons of wrong polarity followed the pathways of axons growing centripetally but in reverse direction. This suggests that the polarity of growing nerve fibers and their course are determined by different factors. Culturing the eyes of embryos from stages 20 to 25 in the presence of antibodies showed that the antibodies penetrated the entire retina with 6 hr. Neither anti-N-CAM nor the T-61 antibody--both recognizing membrane proteins of retinal cells--affected the growth of the eyes in vitro. The development of the axonal pattern in vitro was not affected by incubation with N-CAM-antibodies at concentrations up to 500 micron/ml, whereas the T-61 antibody which is known to block neurite extention in vitro (S. Henke-Fahle, W. Reckhaus, and R. Babiel (l984). "Developmental Neuroscience: Physiological, Pharmacological, and Clinical Aspects," pp. 393-398. Elsevier, Amsterdam/New York) showed inhibition of axonal growth in retina cultures at 50 micron/ml. These results indicate that the eye cultures can be used as a test system for antibodies against antigens which could be involved in axon extension and neurite pathfinding in situ.

Animals↗