Immunoreactive pinopsin in pineal and retinal photoreceptors of various vertebrates

Studies of severe hypoxemic events, defined as an arterial oxygen saturation < 80% greater than 4 s in spontaneously breathing infants, have been limited. The purpose of our study was to examine the distribution of respiratory events that lead to a fall in oximetrically measured oxygen saturation by using breathing patterns, heart rate, and validated pulse oximetry analysis. A total of 161 hypoxemic events were detected in 18 of 30 premature infants studied. Using an inductive plethysmographic based monitor, a total of 460 h of cardiorespiratory monitor recordings were analyzed. Hypoxemic events were categorized as being the direct result of apnea (duration longer than 15 s) or pauses (duration 4-14 s) with either unchanged or lower end-expiratory lung volumes compared with the preevent breaths. The breaths in the preevent period were analyzed for volume, timing, and thoracoabdominal coordination indices. Forty of the 161 events (25%) were associated with apnea of which 80% (31/40) had a mixed/obstructive basis. Ninety-four of the 161 severe hypoxemic events (58%) were associated with pauses with unchanged end-expiratory lung volume. Twenty-two of the 161 events (14%) showed pauses with lower end-expiratory lung volume. There were 5/161 events (3%) with severe hypoxemia in which no pause was observed. Comparison of the preevent periods in each category showed significant differences for only percent tidal volume from initial calibration and arterial oxygen saturation. Sixty-two percent (100/161) of severe hypoxemic events were preceded by hypopneic values of percent tidal volume. Seventy-five percent (40/161) of these hypoxemic events and their etiology would have gone undetected using respiratory monitoring from impedance pneumograms and ECGs. The varied basis for these events underscores the importance of analyzing detailed respiratory wave forms along with movement-free signal of arterial oxygen saturation and ECG, to formulate appropriate intervention strategies.     

Circadian clock functions localized in xenopus retinal photoreceptors

A circadian oscillator that regulates visual function is located somewhere within the vertebrate eye. To determine whether circadian rhythmicity is generated by retinal photoreceptors, we isolated and cultured photoreceptor layers from Xenopus retina. On average, 94% of the viable cells in these preparations were rod or cone photoreceptors. Photoreceptor layers produced melatonin rhythmically, with an average period of 24.3 hr, in constant darkness. The phase of the melatonin rhythm was reset by in vitro exposure of the photoreceptor layers to cycles of either light or quinpirole, a D2 dopamine receptor agonist. These data indicate that other parts of the eye are not necessary for generation or entrainment of retinal circadian melatonin rhythms and suggest that rod and/or cone photoreceptors are circadian clock cells.     

Simplified ganglioside composition of photoreceptors compared to other retinal neurons

PURPOSE: The quantitative and qualitative ganglioside composition of retinal photoreceptor cells is unknown. The aim of this study was to analyze the lipid, especially ganglioside, make-up of photoreceptors compared to other retinal cells. METHODS: Retinas from adult normal rats were mechanically separated into outer (photoreceptors) and inner (other retinal neurons and glia) halves be planar vibratome sectioning. Total lipids were extracted, and each fraction (neural, phospholipids, and glycosphingolipids) was eluted sequentially by column chromatography and quantitated through high-performance thin layer chromatogram analysis. Similar analyses were performed on entire retinas from adult normal rats, adult dystrophic rats lacking photoreceptors (RCS-rdy-p+ strain), and isolated photoreceptor outer segments. RESULTS: Whereas phospholipids were distributed equally between the two halves, inner retina contained significantly more cholesterol (68% total) and gangliosides (74% total) than outer retina on a unit protein basis. The distribution on a percent molar basis of specific gangliosides also was significantly different between the two halves: Outer retina was dominated by GD3 (45% total ganglioside) and contained only trace amounts (<4%) of complex species (GT1b and GQ1b); inner retina was more typical of mature brain tissue exhibiting substantial amounts (approximately 25%) of more complex species. These data were supported by lipid compositional analyses of mutant photoreceptor-less retina. However, isolated outer segments resembled whole retina in containing higher levels of complex gangliosides. CONCLUSIONS: These data indicate that, compared to other central nervous system-derived neurons, photoreceptor cell body membranes exhibit a highly unusual simplified ganglioside composition. Such an unusual neuronal lipid composition may reflect structural adaptations to their specialized function.     

Cellular and molecular regulation of serotonin N-acetyltransferase activity in chicken retinal photoreceptors

Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and large changes in the activity of this enzyme appear to regulate the rhythm in melatonin synthesis. Recent advances have made it possible to study the mRNA encoding chicken AA-NAT, which has only been detected in the retina and pineal gland. Within the retina, AA-NAT mRNA is expressed primarily in photoreceptors. The levels of chicken retinal AA-NAT mRNA and activity exhibit 24-hour rhythms with peaks at night. These rhythms appear to reflect circadian clock control of AA-NAT mRNA abundance and independent effects of light and darkness on both mRNA levels and enzyme activity. The effects of darkness and light may occur through alterations in cAMP-dependent protein phosphorylation, which increases AA-NAT activity in photoreceptor cell cultures. The cAMP-dependent increase of AA-NAT enzyme activity reflects, at least in part, increased mRNA levels and inhibition of enzyme inactivation by a posttranslational mechanism. This review discusses a hypothetical model for the cellular and molecular regulation of AA-NAT activity by circadian oscillators and light in chicken retinal photoreceptor cells.     

Molecular properties of the cGMP-gated channel of rod photoreceptors

The cGMP-gated channel of the rod photoreceptor cell plays a key role in phototransduction by controlling the flow of Na+ and Ca2+ into the outer segment in response to light-induced changes in cGMP concentrations. The rod channel is composed of two homologous subunits designated as alpha and beta. Each subunit contains a core region of six putative membrane spanning segments, a cGMP binding domain, a voltage sensor-like motif and a pore region. In addition the beta-subunit contains an extended N-terminal region that is identical in sequence to a previously cloned retinal glutamic acid rich protein called GARP. Three spliced variants of GARP (the GARP part of the beta channel subunit; full length free GARP; and a truncated form of GARP) are expressed in rod cells and localized within the outer segments. Immunoaffinity chromatography has been used to purify the channel from detergent solubilized rod outer segments. A significant fraction of the rod Na+/Ca(2+)-K+ exchanger copurifies with the channel as measured by western blotting suggesting that the channel can interact with the exchanger under certain conditions.     

Effects of animal age on the responses along the outer segment of retinal rod photoreceptors

The aim of the present study was to determine whether the response gradient, known to exist along a rod outer segment, is influenced by age and developmental changes. Since intense light flashes saturate the responses of retinal rods and the time the response remains saturated increases from base to tip of the rod outer segment, one can use this difference in saturation times as a measure of the response gradient. During development and before sexual maturity (about one year postmetamorphosis) the differences between base and tip decreased, and this correlated with an acceleration of the light response in Xenopus laevis rods. The gradient along the rod outer segment then stabilized, while the response kinetics slowed and remained at a lower level. We conclude that photoreceptor responses and hence visual performance are affected by developmental changes.     

The melatonin antagonist luzindole protects retinal photoreceptors from light damage in the rat

PURPOSE: Systemic administration of melatonin can increase retinal light damage in the rat. The role of retinal melatonin receptors in modulating light-damage susceptibility was investigated by intravitreally injecting the melatonin receptor antagonist luzindole into rats. METHODS: Nine Sprague-Dawley albino rats 8 to 9 weeks of age were kept in 50 lux cyclic light for at least 7 days before receiving an intravitreal injection of 1 microl 1 mM luzindole in one eye and 1 microl vehicle in the other eye. The injection was given just before the beginning of the normal 12-hour dark phase. At the end of this dark period, animals were exposed to constant light of 2500 lux for 48 hours. Animals were returned to dim cyclic light for 7 days, and dark-adapted electroretinograms (ERGs) were then recorded from the two eyes simultaneously. The eyes were processed for retinal morphology. Photoreceptor nuclei were counted in the outer nuclear layer (ONL), and the thickness of the ONL and that of the rod outer-segment plus inner-segment layer were measured at several points along sections through the vertical meridian. Two age-matched control rats were maintained in dim cyclic light but received no injections. RESULTS: Luzindole-treated eyes had ERG b-wave thresholds of 2.7 +/- 0.5 (mean +/- SEM) log candela (cd)/m2 lower than the fellow eyes injected with vehicle (P < 0.001), and the maximum b-wave amplitude was 1.0 +/- 0.2 log microV greater in luzindole-treated eyes (P < 0.001). Thresholds of the scotopic threshold response were 0.5 +/- 0.1 log cd/m2 lower than those in vehicle-injected eyes (P < 0.05). Luzindole-treated eyes on average had twice as many photoreceptor cells remaining (P < 0.005). In some areas, several rows of photoreceptor nuclei and outer segments remained in the luzindole-treated eye, whereas the fellow control eye showed cells only occasionally and no outer segments. CONCLUSIONS: Eyes pretreated with the melatonin receptor competitive antagonist luzindole before the dark phase preceding constant light exposure were substantially protected from light damage to the retinal photoreceptors. These results implicate the intraocular melatonin-dopamine system in the regulation of light-damage susceptibility.     

Physical properties of the retinal receptor and response of retinal receptors.

The author reviews studies of the waveguide characteristics of retinal receptors. These properties are present in human photoreceptors. Some of the possible roles played by these physical properties are discussed, with emphasis placed upon color-vision mechanisms at the receptor level. The author also considers approaches toward the determination of the role(s) played by the waveguide properties, by the photosensitive pigments, and by "other" mechanisms in the coding of the signal at the detector level. He describes his initial experiments directed toward the development of an indicator of response (or marker) in single mammalian retinal receptors. (629 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ca2+ induces an increase in cGMP-phosphodiesterase activity in squid retinal photoreceptors

In this paper we describe a rapid, isocratic high performance liquid chromatography (HPLC) method for the study of radioactive fatty acid incorporation into complex lipids of human erythrocytes, which allows the simultaneous separation of the major phospholipid classes and long-chain acylcarnitines. The lipid extract of erythrocytes pulsed with radioactive fatty acids was injected into an HPLC system equipped with a silica column. The individual components eluted were monitored by ultraviolet absorption and radioactive emission. With respect to the UV profile, the radioactive profile showed an additional peak between phosphatidyl-choline and phosphatidylethanolamine, which was identified as long-chain acylcarnitine by different experimental approaches. The radioactivity recovered in the long-chain acylcarnitines contains essential information enabling definition of acyl trafficking in red cells.     

Optical basicity and the thermodynamic properties of slags

Metallurgical and Materials Transactions B -     

The effect of peripherin/rds haploinsufficiency on rod and cone photoreceptors

Haploinsufficiency because of a null mutation in the gene encoding peripherin/rds has been thought to be the primary defect associated with the photoreceptor degeneration seen in the retinal degeneration slow (rds) mouse. We have compared the effects of this haploinsufficiency on rod and cone photoreceptors by measuring the levels of rod- and cone-specific gene expression, by determining the relative rates of rod and cone degeneration, and by electroretinography. These analyses were performed at ages before and after the onset of degeneration of the photoreceptor cells. The data were consistent in demonstrating that measures for cone photoreceptors are relatively spared in comparison to comparable measures for rod photoreceptors. Blue cones were retained in higher number than red/green cones for the first 3 months of the degeneration. Our results indicate that the haploinsufficiency present in rds/+ mice has a greater impact on the rod than on the cone photoreceptor, a finding that likely reflects the tight regulation of peripherin/rds and the need for two functional alleles to assemble the structure of the rod outer segment and/or differences between the ultrastructure of the rod and cone outer segments.     

Fourth module of Xenopus interphotoreceptor retinoid-binding protein: activity in retinoid transfer between the retinal pigment epithelium and rod photoreceptors

PURPOSE: Interphotoreceptor retinoid-binding protein (IRBP), an extracellular protein believed to support the exchange of retinoids between the neural retina and retinal pigment epithelium (RPE) in the vertebrate eye, exhibits a modular, i.e., repeat, structure. The present study was undertaken to determine whether an individual module of IRBP has activity in retinoid transfer between the RPE and rod photoreceptors. METHODS: The retinoid transfer activity of a recombinant protein corresponding to the fourth module of Xenopus laevis IRBP (X4IRBP) was examined in two ways. First, X4IRBP was tested for its ability to support the regeneration of porphyropsin in detached/reattached Xenopus retina/RPE-eyecups. Following illumination and removal of native IRBP, Xenopus eyecups supplemented with 42 microM X4IRBP or (as a control) Ringer's solution were incubated in darkness and then analyzed for regenerated porphyropsin. Second, toad (Bufo marinus) RPE-eyecup preparations were used to evaluate X4IRBP's ability to promote the release of 11-cis retinal from the RPE. RESULTS: The regeneration of porphyropsin in X4IRBP-supplemented Xenopus retina/RPE-eyecups (0.45 +/- 0.04 nmol; mean +/- SEM, n = 11) exceeded that in controls (0.13 +/- 0.02 nmol, n = 11). For promoting the release of 11-cis retinal from the toad RPE, 42 microM X4IRBP was more effective than equimolar bovine serum albumin although considerably less than that of 26 microM native bovine IRBP. CONCLUSIONS: The results indicate a low but significant activity of IRBP's fourth module in reactions relevant to retinoid exchange.