Reduction of All-trans Retinal to All-trans Retinol in the Outer Segments of Frog and Mouse Rod Photoreceptors

Chen, Chunhe; Tsina, Efthymia; Cornwall, M. Carter; Crouch, Rosalie K.; Vijayaraghavan, Sukumar; Koutalos, Yiannis

doi:10.1529/biophysj.104.054254

Cited by 65 publications

(88 citation statements)

References 42 publications

(53 reference statements)

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“…7). Elegant studies of retinoid processing in retina slices and isolated photoreceptor cells have shown that all-trans-retinol formation localizes to the outer segments during recovery from bleaching (40,58). Of the RDH isoforms known to be expressed in retina, only RDH8 has been localized to the outer segments (51,57).…”

Section: Discussionmentioning

confidence: 99%

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Chrispell¹,

Feathers

Kane

et al. 2009

Journal of Biological Chemistry

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RDH12 mutations are responsible for early-onset autosomal recessive retinal dystrophy, which results in profound retinal pathology and severe visual handicap in patients. To investigate the function of RDH12 within the network of retinoid dehydrogenases/reductases (RDHs) present in retina, we studied the retinal phenotype of Rdh12-deficient mice. In vivo rates of alltrans-retinal reduction and 11-cis-retinal formation during recovery from bleaching were similar in Rdh12-deficient and wild-type mice matched for an Rpe65 polymorphism that impacts visual cycle efficiency. However, retinal homogenates from Rdh12-deficient mice exhibited markedly decreased capacity to reduce exogenous retinaldehydes in vitro. Furthermore, in vivo levels of the bisretinoid compound diretinoid-pyridinium-ethanolamine (A2E) were increased in Rdh12-deficient mice of various genetic backgrounds. Conversely, in vivo levels of retinoic acid and total retinol were significantly decreased. Rdh12 transcript levels in wild-type mice homozygous for the Rpe65-Leu 450 polymorphism were greater than in Rpe65-Met 450 mice and increased during postnatal development in wild-type mice and Nrl-deficient mice having an all-cone retina. Rdh12-deficient mice did not exhibit increased retinal degeneration relative to wild-type mice at advanced ages, when bred on the lightsensitive BALB/c background, or when heterozygous for a null allele of superoxide dismutase 2 (Sod2 ؉/؊ ). Our findings suggest that a critical function of RDH12 is the reduction of all-trans-retinal that exceeds the reductive capacity of the photoreceptor outer segments.RDH12 is a major disease gene for Leber congenital amaurosis, with RDH12 mutations responsible for approximately 2% of cases of childhood-onset severe autosomal recessive retinal dystrophy (1-4). Affected individuals experience poor vision in early life, which progressively declines with age as a result of both rod and cone degeneration (5). Analyses of retinal organization and visual function in patients with mutations in RDH12 or RPE65, another Leber congenital amaurosis gene involved in retinoid metabolism, show distinctly different pathologies associated with defects in each gene that will be important to consider when developing targeted forms of therapy (6).RDH12 encodes a member of the family of short chain dehydrogenases/reductases that catalyze oxidation and reduction reactions involved in various aspects of metabolism (reviewed in Refs. 7 and 8). In the photoreceptor cells and retinal pigment epithelium (RPE), 3 the interconversion of oxidized and reduced retinoids by RDH enzymes is an important feature of the visual cycle, the process responsible for the conversion of vitamin A (all-trans-retinol) to 11-cis-retinal, the chromophore of the visual pigments (reviewed in Ref. 9). On the basis of in vitro assays showing reactivity toward retinaldehyde substrates and expression in photoreceptor cells, RDH12 was initially proposed to function in the reduction of all-trans-retinal released by bleached visual pigments (10...

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Section: Discussionmentioning

confidence: 99%

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Chrispell¹,

Feathers

Kane

et al. 2009

Journal of Biological Chemistry

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“…Fluorescence imaging experiments on isolated frog rod photoreceptor cells were carried out with slight modifications of previous procedures (23). Chambers containing dark-adapted cells were placed on the stage of an inverted Zeiss Axiovert 100 microscope (Carl Zeiss, Thornwood, NY) and imaged with a Zeiss 40× Plan Neofluar oil immersion objective lens (N.A.…”

Section: Methodsmentioning

confidence: 99%

“…Retinol fluorescence was excited with 360 nm light using a Xenon continuous arc light source from Sutter Instrument Company (Novato, CA), and the fluorescence image (emission >420 nm) was acquired with a Hamamatsu CCD camera (Hamamatsu Photonics, Hamamatsu-City, Japan). Only metabolically competent cells (23,26) were used for retinol fluorescence imaging experiments. Most of the cells are expected to be the rhodopsin-containing "red" rods, which comprise the overwhelming majority of the rod population in frog retinas (27).…”

Section: Methodsmentioning

confidence: 99%

“…Image acquisition and analysis were carried out using the Intelligent Imaging Innovations (Denver, CO) software. The increase in the outer segment fluorescence after rhodopsin bleaching is due to retinol (23). Fluorescence intensity was measured over defined regions of interest (ROI) contained in the outer segment and background.…”

Section: Methodsmentioning

confidence: 99%

“…One, in contrast to larval salamander photoreceptors that contain two types of chromophore (based on vitamins A 1 and A 2 ) and in widely varying ratios (24), frog rods contain a single, vitamin A 1 -based chromophore. Two, the metabolic supply of NADPH is not limiting for the formation of all-trans retinol in the case of frog rods (23), allowing a simplified analysis and direct comparisons between biochemical and physiological data. This has further allowed us to properly characterize the removal of all-trans retinol by different lipophilic carriers.…”

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confidence: 99%

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Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Blakeley

Cornwall

et al. 2007

Biochemistry

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Light detection by vertebrate rod photoreceptor outer segments results in the destruction of the visual pigment, rhodopsin, as its retinyl moiety is photoisomerized from 11-cis to all-trans. The regeneration of rhodopsin is necessary for vision and begins with the release of the all-trans retinal and its reduction to all-trans retinol. Retinol is then transported out of the rod outer segment for further processing. We used fluorescence imaging to monitor retinol fluorescence and quantify the kinetics of its formation and clearance after rhodopsin bleaching in the outer segments of living isolated frog (Rana pipiens) rod photoreceptors. We independently measured the release of all-trans retinal from bleached rhodopsin in frog rod outer segment membranes and the rate of all-trans retinol removal by the lipophilic carriers interphotoreceptor retinoid binding protein (IRBP) and serum albumin. We find that the kinetics of all-trans retinol formation in frog rod outer segments after rhodopsin bleaching are to a good first approximation determined by the kinetics of all-trans retinal release from the bleached pigment. For the physiological concentrations of carriers, the rate of retinol removal from the outer segment is determined by the IRBP concentration, while the effect of serum albumin is negligible. The results indicate the presence of a specific interaction between IRBP and rod outer segment, probably mediated by a receptor. The effect of different concentrations of IRBP on the rate of retinol removal shows no cooperativity and has an EC 50 of 40 μmol/L.The vertebrate cells responsible for vision are the rod and cone photoreceptors of the retina that convert incoming light to an electrical signal. This conversion takes place in the photoreceptor outer segments, which are full of membrane disks containing the visual pigment, and, in a physiologically important arrangement, are enveloped by the retinal pigment epithelium (RPE). The visual pigment is composed of a chromophore, 11-cis retinal, attached to an integral membrane protein, opsin. The detection of light begins with the absorption of incoming photons by the visual pigment. An absorbed photon isomerizes the chromophore † Supported by NIH/NEI grants EY14850 (YK), EY04939 (RKC) , NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript moiety from 11-cis to all-trans bringing about a conformational change that initiates a cascade of reactions culminating in membrane potential change. The recovery of the cell from light involves the deactivation of the intermediates activated by light, and the reestablishment of membrane potential (1,2). However, the isomerized chromophore, all-trans retinal, remains. For vision to be possible, it is essential that the visual pigment regenerate: that is, the alltrans retinal has to be removed, and fresh 11-cis retinal has to be provided to combine with opsin and reform the visual pigment. The reactions regenerating the pigment are known as the Visual Cycle (3-5).In the case of the rod photoreceptors, t...

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Influence of Arrestin on the Photodecay of Bovine Rhodopsin

et al. 2015

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Continued activation of the photocycle of the dim-light receptor rhodopsin leads to accumulation of all-trans-retinal in rod outer segments (ROS). This accumulation can damage the photoreceptor cell. For retinal homeostasis, deactivation processes are initiated in which the release of retinal is delayed. One of the processes involves binding of arrestin to rhodopsin. Here, we investigate the interaction of pre-activated truncated bovine visual arrestin (Tr) with rhodopsin in 1,2diheptanoyl-sn-glycero-3-phosphocholine (DHPC) micelles by solution NMR techniques and flash photolysis spectroscopy. Our results show that formation of the rhodopsin-arrestin complex markedly influences partitioning in the decay kinetics of rhodopsin that involves the simultaneous formation of meta II state and meta III state from the meta I state. Binding of Tr leads to an increase of meta III state population and consequently to a ~2-fold slower release of all-transretinal from rhodopsin.

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Reduction of All-trans Retinal to All-trans Retinol in the Outer Segments of Frog and Mouse Rod Photoreceptors

Cited by 65 publications

References 42 publications

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Influence of Arrestin on the Photodecay of Bovine Rhodopsin

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