Intra-retinal visual cycle required for rapid and complete cone dark adaptation

Wang, Jinshan; Estevez, Maureen E.; Cornwall, M. Carter; Kefalov, Vladimir J.

doi:10.1038/nn.2258

Cited by 118 publications

(137 citation statements)

References 34 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…Even in humans, there is likely enough transmitted blue light in full sunlight for OPN5 to signal, because OPN5's sensitivity at the human blue cone pigment's λ max of 430 nm is only one log-unit lower than at its own λ max of 380 nm [based on heterologous expression (13,16)]. The cis-retinal required by OPN5 as a chromophore (13, 16) could potentially be accessed in the inner retina in the same way as by ipRGCs, possibly from the Müller glial cells (41). For corneal OPN5, interphotoreceptor retinoid-binding protein in the aqueous and vitreous humors (42) could potentially transport cis-retinal via diffusion from the retina.…”

Section: Discussionmentioning

confidence: 99%

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

Buhr

Yue

Ren

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

125

181

View full text Add to dashboard Cite

The molecular circadian clocks in the mammalian retina are locally synchronized by environmental light cycles independent of the suprachiasmatic nuclei (SCN) in the brain. Unexpectedly, this entrainment does not require rods, cones, or melanopsin (OPN4), possibly suggesting the involvement of another retinal photopigment. Here, we show that the ex vivo mouse retinal rhythm is most sensitive to short-wavelength light but that this photoentrainment requires neither the short-wavelength-sensitive cone pigment [S-pigment or cone opsin (OPN1SW)] nor encephalopsin (OPN3). However, retinas lacking neuropsin (OPN5) fail to photoentrain, even though other visual functions appear largely normal. Initial evidence suggests that OPN5 is expressed in select retinal ganglion cells. Remarkably, the mouse corneal circadian rhythm is also photoentrainable ex vivo, and this photoentrainment likewise requires OPN5. Our findings reveal a light-sensing function for mammalian OPN5, until now an orphan opsin.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

Buhr

Yue

Ren

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

125

181

View full text Add to dashboard Cite

show abstract

“…First, it should show higher catalytic efficiency toward 11-cis-ROL versus 9-cis-ROL, 13-cis-ROL, and all-trans-ROL substrates. Second, it should be expressed in Müller cells, which also express CRALBP (19) and DES1 (11), and are the cellular loci of the noncanonical visual cycle (9,10). Finally, the enzyme should show cooperativity with DES1 for conversion of all-trans-ROL to 11-cis-RP.…”

Section: Discussionmentioning

confidence: 99%

“…A second visual cycle is present in Müller cells of the retina, providing 11-cis-ROL to cones (9)(10)(11). Cones, but not rods, can use 11-cis-ROL as a chromophore precursor to regenerate bleached opsin pigments (10,12,13).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of the 11- cis- specific retinyl-ester synthase in retinal Müller cells as multifunctional O- acyltransferase (MFAT)

Kaylor¹,

Cook²,

Makshanoff³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.L ight perception begins with the absorption of a photon by an opsin pigment in the membranous outer segment (OS) of a rod or cone photoreceptor cell. The light-absorbing chromophore in most vertebrate opsins is 11-cis-retinaldehyde (11-cis-RAL). Photon capture isomerizes the 11-cis-RAL to all-trans-retinaldehyde (all-trans-RAL), inducing conformational changes in the protein that lead to its active meta-II state. After a brief period of signaling through the transduction cascade, meta II decays to yield apo-opsin and free all-trans-RAL. Light sensitivity is restored to the apo-opsin when it combines with 11-cis-RAL to regenerate the pigment. Conversion of all-trans-RAL to 11-cis-RAL is carried out by a multistep enzyme pathway called the visual cycle, located in cells of the retinal pigment epithelium (RPE) (1, 2). The retinoid isomerase in this pathway is Rpe65, which converts an all-transretinyl ester (all-trans-RE), such as all-trans-retinyl palmitate (alltrans-RP), to 11-cis-retinol (11-cis-ROL) and a free fatty acid (3-5). Retinyl esters are synthesized in RPE cells by lecithin:retinol acyl transferase (LRAT), which transfers a fatty acid from phosphatidylcholine to retinol (6, ...

show abstract

“…3. This is partly due to a relatively large reservoir of chromophore in the large outer segment volume but may also reflect the ability of Müller cells to regenerate 11-cis-retinal for cones 12 .…”

Section: Amphibian Saline Presynaptic Pipette Postsynaptic Pipettementioning

confidence: 99%

Simultaneous Whole-cell Recordings from Photoreceptors and Second-order Neurons in an Amphibian Retinal Slice Preparation

Hook

Thoreson

2013

JoVE

View full text Add to dashboard Cite

One of the central tasks in retinal neuroscience is to understand the circuitry of retinal neurons and how those connections are responsible for shaping the signals transmitted to the brain. Photons are detected in the retina by rod and cone photoreceptors, which convert that energy into an electrical signal, transmitting it to other retinal neurons, where it is processed and communicated to central targets in the brain via the optic nerve. Important early insights into retinal circuitry and visual processing came from the histological studies of Cajal 1,2 and, later, from electrophysiological recordings of the spiking activity of retinal ganglion cells -the output cells of the retina 3,4 .A detailed understanding of visual processing in the retina requires an understanding of the signaling at each step in the pathway from photoreceptor to retinal ganglion cell. However, many retinal cell types are buried deep in the tissue and therefore relatively inaccessible for electrophysiological recording. This limitation can be overcome by working with vertical slices, in which cells residing within each of the retinal layers are clearly visible and accessible for electrophysiological recording.Here, we describe a method for making vertical sections of retinas from larval tiger salamanders (Ambystoma tigrinum). While this preparation was originally developed for recordings with sharp microelectrodes 5,6 , we describe a method for dual whole-cell voltage clamp recordings from photoreceptors and second-order horizontal and bipolar cells in which we manipulate the photoreceptor's membrane potential while simultaneously recording post-synaptic responses in horizontal or bipolar cells. The photoreceptors of the tiger salamander are considerably larger than those of mammalian species, making this an ideal preparation in which to undertake this technically challenging experimental approach. These experiments are described with an eye toward probing the signaling properties of the synaptic ribbon -a specialized synaptic structure found in a only a handful of neurons, including rod and cone photoreceptors, that is well suited for maintaining a high rate of tonic neurotransmitter release 7,8 -and how it contributes to the unique signaling properties of this first retinal synapse. Video LinkThe video component of this article can be found at https://www.jove.com/video/50007/ Protocol Retinal Slices Preparation1. Assemble the chamber (design illustrated in Figure 1). Place two beads of vacuum grease, spaced ~8-10 mm apart, across the recording chamber to form a channel for superfusate and in which to embed the retinal slices. Add a second bead of grease a few millimeters farther out beyond each of these two beads of grease to act as a levee and limit spillover. Place a small triangular piece of KimWipe at the end of the chamber to ensure fluid contact with the reference electrode. 2. Press a piece of nitrocellulose membrane (~ 5 x 10 mm; 0.8 μm pores) flat against the glass microscope slide into two small beads of vacuum gre...

show abstract

Intra-retinal visual cycle required for rapid and complete cone dark adaptation

Cited by 118 publications

References 34 publications

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

Identification of the 11- cis- specific retinyl-ester synthase in retinal Müller cells as multifunctional O- acyltransferase (MFAT)

Simultaneous Whole-cell Recordings from Photoreceptors and Second-order Neurons in an Amphibian Retinal Slice Preparation

Contact Info

Product

Resources

About