The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones

Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones

Chromophore supply rate-limits mammalian photoreceptor dark adaptation

Efficient regeneration of visual pigment following its destruction by light is critical for the function of mammalian photoreceptors. Here, we show that misexpression of a subset of cone genes in the rd7 mouse hybrid rods enables them to access the normally cone-specific retina visual cycle. The rapid supply of chromophore by the retina visual cycle dramatically accelerated the mouse rod dark adaptation. At the same time, the competition between rods and cones for retina-derived chromophore slowed cone dark adaptation, indicating that the cone specificity of the retina visual cycle is key for rapid cone dark adaptation. Our findings demonstrate that mammalian photoreceptor dark adaptation is dominated by the supply of chromophore. Misexpression of cone genes in rods may represent a novel approach to treating visual disorders associated with mutations of visual cycle proteins or with reduced retinal pigment epithelium function due to aging

Optics of cone photoreceptors in the chicken (Gallus gallus domesticus)

Vision is the primary sensory modality of birds, and its importance is evident in the sophistication of their visual systems. Coloured oil droplets in the cone photoreceptors represent an adaptation in the avian retina, acting as long-pass colour filters. However, we currently lack understanding of how the optical properties and morphology of component structures (e.g. oil droplet, mitochondrial ellipsoid and outer segment) of the cone photoreceptor influence the transmission of light into the outer segment and the ultimate effect they have on receptor sensitivity. In this study, we use data from microspectrophotometry, digital holographic microscopy and electron microscopy to inform electromagnetic models of avian cone photoreceptors to quantitatively investigate the integrated optical function of the cell. We find that pigmented oil droplets primarily function as spectral filters, not light collection devices, although the mitochondrial ellipsoid improves optical coupling between the inner segment and oil droplet. In contrast, unpigmented droplets found in violet-sensitive cones double sensitivity at its peak relative to other cone types. Oil droplets and ellipsoids both narrow the angular sensitivity of single cone photoreceptors, but not as strongly as those in human cones

Whole-grain products and whole grain types are associated with lower all-cause and cause-specific mortality in the Scandinavian HELGA cohort

No study has yet investigated the intake of different types of whole grain (WG) in relation to all-cause and cause-specific mortality in a healthy population. The aim of the present study was to investigate the intake of WG products and WG types in relation to all-cause and cause-specific mortality in a large Scandinavian HELGA cohort that, in 1992–8, included 120 010 cohort members aged 30–64 years from the Norwegian Women and Cancer Study, the Northern Sweden Health and Disease Study, and the Danish Diet Cancer and Health Study. Participants filled in a FFQ from which data on the intake of WG products were extracted. The estimation of daily intake of WG cereal types was based on country-specific products and recipes. Mortality rate ratios (MRR) and 95 % CI were estimated using the Cox proportional hazards model. A total of 3658 women and 4181 men died during the follow-up (end of follow-up was 15 April 2008 in the Danish sub-cohort, 15 December 2009 in the Norwegian sub-cohort and 15 February 2009 in the Swedish sub-cohort). In the analyses of continuous WG variables, we found lower all-cause mortality with higher intake of total WG products (women: MRR 0·89 (95 % CI 0·86, 0·91); men: MRR 0·89 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, intake of breakfast cereals and non-white bread was associated with lower mortality. We also found lower all-cause mortality with total intake of different WG types (women: MRR 0·88 (95 % CI 0·86, 0·92); men: MRR 0·88 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, WG oat, rye and wheat were associated with lower mortality. The associations were found in both women and men and for different causes of deaths. In the analyses of quartiles of WG intake in relation to all-cause mortality, we found lower mortality in the highest quartile compared with the lowest for breakfast cereals, non-white bread, total WG products, oat, rye (only men), wheat and total WG types. The MRR for highestv.lowest quartile of intake of total WG products was 0·68 (95 % CI 0·62, 0·75,Ptrend over quartiles&lt; 0·0001) for women and 0·75 (95 % CI 0·68, 0·81,Ptrend over quartiles&lt; 0·0001) for men. The MRR for highestv.lowest quartile of intake of total WG types was 0·74 (95 % CI 0·67, 0·81,Ptrend over quartiles&lt; 0·0001) for women and 0·75 (95 % CI 0·68, 0·82,Ptrend over quartiles&lt; 0·0001) for men. Despite lower statistical power, the analyses of cause-specific mortality according to quartiles of WG intake supported these results. In conclusion, higher intake of WG products and WG types was associated with lower mortality among participants in the HELGA cohort. The study indicates that intake of WG is an important aspect of diet in preventing early death in Scandinavia.</jats:p

Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds

Color vision in birds is mediated by four types of cone photoreceptors whose maximal sensitivities (λmax) are evenly spaced across the light spectrum. In the course of avian evolution, the λmax of the most shortwave-sensitive cone, SWS1, has switched between violet (λmax > 400 nm) and ultraviolet (λmax < 380 nm) multiple times. This shift of the SWS1 opsin is accompanied by a corresponding short-wavelength shift in the spectrally adjacent SWS2 cone. Here, we show that SWS2 cone spectral tuning is mediated by modulating the ratio of two apocarotenoids, galloxanthin and 11',12'-dihydrogalloxanthin, which act as intracellular spectral filters in this cell type. We propose an enzymatic pathway that mediates the differential production of these apocarotenoids in the avian retina, and we use color vision modeling to demonstrate how correlated evolution of spectral tuning is necessary to achieve even sampling of the light spectrum and thereby maintain near-optimal color discrimination

Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods

Photoactivation of vertebrate rhodopsin converts it to the physiologically active Meta II (R*) state, which triggers the rod light response. Meta II is rapidly inactivated by the phosphorylation of C-terminal serine and threonine residues by G-protein receptor kinase (Grk1) and subsequent binding of arrestin 1 (Arr1). Meta II exists in equilibrium with the more stable inactive form of rhodopsin, Meta III. Dark adaptation of rods requires the complete thermal decay of Meta II/Meta III into opsin and all-trans retinal and the subsequent regeneration of rhodopsin with 11-cis retinal chromophore. In this study, we examine the regulation of Meta III decay by Grk1 and Arr1 in intact mouse rods and their effect on rod dark adaptation. We measure the rates of Meta III decay in isolated retinas of wild-type (WT), Grk1-deficient (Grk1(−/−)), Arr1-deficient (Arr1(−/−)), and Arr1-overexpressing (Arr1(ox)) mice. We find that in WT mouse rods, Meta III peaks ∼6 min after rhodopsin activation and decays with a time constant (τ) of 17 min. Meta III decay slows in Arr1(−/−) rods (τ of ∼27 min), whereas it accelerates in Arr1(ox) rods (τ of ∼8 min) and Grk1(−/−) rods (τ of ∼13 min). In all cases, regeneration of rhodopsin with exogenous 11-cis retinal is rate limited by the decay of Meta III. Notably, the kinetics of rod dark adaptation in vivo is also modulated by the levels of Arr1 and Grk1. We conclude that, in addition to their well-established roles in Meta II inactivation, Grk1 and Arr1 can modulate the kinetics of Meta III decay and rod dark adaptation in vivo

Ommatidial adaptations for vision in nocturnal insects

Nocturnal vision is a demanding task for insects with small eyes. As it gets dimmer the noise imposed by the stochastic nature of photon arrival makes vision unreliable. Despite this, there are quite a number of animal species that are active at night and apparently see well. In this thesis I show that the compound eyes of nocturnal insects are sufficiently flexible to adapt to the particular window of intensities in which the species is active. These ommatidial adaptations for vision in nocturnal insects are found in the optics and morphology of the eye (Chapters I - III) and in the physiology of the photoreceptors (Chapters IV & V). I have also discovered that the various visual adaptations that optimise sensitivity in a compound eye, and thus adapt the eye for a crepuscular or nocturnal lifestyle, do not contribute equally in different groups of insects. The crepuscular Caligo memnon has evolved large eyes with large facets but retained a reasonably high spatial and temporal resolution. In the nocturnal bee Megalopta genalis, the eyes and facets are enlarged, the rhabdoms are wide and the spatial and temporal acuity very poor compared to diurnal insects. In addition to this, M. genalis has a high gain of transduction present in its photoreceptors. The nocturnal dung beetle Onitis aygulus has refracting superposition eyes and increases optical sensitivity by possessing a wide superposition aperture. In addition, this beetle has slow photoreceptors with high gain. Thus, there are a variety of solutions to improve visual sensitivity and reliability in dim light. Exactly which solution evolved in which group most likely depends on constraints imposed by different phylogenetic histories, developmental constraints and different selection pressures due to different life styles

Visual sensitivity in the crepuscular owl butterfly Caligo memnon and the diurnal blue morpho Morpho peleides: a clue to explain the evolution of nocturnal apposition eyes?

Insects active in dim light, such as moths and many beetles, normally have superposition compound eyes to increase photon capture. But there are nocturnal and crepuscular insects - such as some species of bees, wasps and butterflies - that have apposition compound eyes. These are likely to have adaptations - including large eye and facet size and coarsened spatial and temporal resolution - that improve their sensitivity and thus their visual reliability. Is this also true for crepuscular insects that are active at intermediate intensities? To test this hypothesis, the visual performance of two closely related butterflies, the diurnal blue morpho Morpho peleides and the crepuscular owl butterfly Caligo memnon, were compared. Compared to the diurnal M. peleides, the crepuscular C. memnon does not appear to be adapted to a nocturnal lifestyle in terms of spatial resolution: the interommatidial angle Delta is similar in both species, and acceptance angles, Deltarho, are only marginally larger in C. memnon. Moreover, temporal resolution is only a little coarser in C. memnon compared to M. peleides. Using a model for sensitivity, we found that the eyes of C. memnon are about four times as light-sensitive as those of M. peleides in the frontal visual field, much of this difference being due to the larger facet diameters found in C. memnon. In summary, greater visual sensitivity has evolved in C. memnon than in M. peleides, showing that adaptations that improve sensitivity can be found not only in nocturnal apposition eyes, but also on a smaller scale in crepuscular apposition eyes