scholarly journals Imaging outer segment renewal in living human cone photoreceptors

2010 ◽  
Vol 18 (5) ◽  
pp. 5257 ◽  
Author(s):  
Ravi S. Jonnal ◽  
Jason R. Besecker ◽  
Jack C. Derby ◽  
Omer P. Kocaoglu ◽  
Barry Cense ◽  
...  
Keyword(s):  
Outer Segment ◽  
Cone Photoreceptors

PRCD is Concentrated at the Base of Photoreceptor Outer Segments and is Involved in Outer Segment Disc Formation

2019 ◽  
Author(s):  
Gilad Allon ◽  
Irit Mann ◽  
Lital Remez ◽  
Elisabeth Sehn ◽  
Leah Rizel ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Knockout Mice ◽  
Outer Segment ◽  
Mouse Retina ◽  
Cone Photoreceptors ◽  
Photoreceptor Outer Segment ◽  
Photoreceptor Outer Segments ◽  
Outer Segments ◽  
Rod And Cone Photoreceptors ◽  
Disc Formation

Abstract Mutations of the PRCD gene are associated with rod-cone degeneration in both dogs and humans. Prcd is expressed in the mouse eye as early as embryonic day 14. In the adult mouse retina PRCD is expressed in the outer segments of both rod and cone photoreceptors. Immunoelectron microscopy revealed that PRCD is located at the outer segment rim, and that it is highly concentrated at the base of the outer segment. Prcd-knockout mice present with progressive retinal degeneration, starting at 20 weeks of age and onwards. This process is reflected by a significant and progressive reduction of both scotopic and photopic electroretinographic responses, and by thinning of the retina, and specifically of the outer nuclear layer, indicating photoreceptor loss. Electron microscopy revealed severe damage to photoreceptor outer segments, which is associated with immigration of microglia cells to the Prcd-knockout retina, and accumulation of vesicles in the inter-photoreceptor space. Phagocytosis of photoreceptor outer segment discs by the retinal pigmented epithelium is severely reduced. Our data show that Prcd-knockout mice serve as a good model for retinal degeneration caused by PRCD mutations in humans. Our findings in these mice support the involvement of PRCD in outer segment disc formation of both rod and cone photoreceptors. Furthermore, they suggest a feedback mechanism which coordinates the rate of photoreceptor outer segment disc formation, shedding and phagocytosis. This study has important implications for understanding the function of PRCD in the retina, as well as for future development of treatment modalities for PRCD-deficiency in humans.

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

2015 ◽  
Vol 12 (111) ◽  
pp. 20150591 ◽  
Author(s):  
David Wilby ◽  
Matthew B. Toomey ◽  
Peter Olsson ◽  
Rikard Frederiksen ◽  
M. Carter Cornwall ◽  
...  
Keyword(s):  
Outer Segment ◽  
Sensory Modality ◽  
Digital Holographic Microscopy ◽  
Cone Photoreceptors ◽  
Oil Droplets ◽  
Oil Droplet ◽  
Integrated Optical ◽  
Single Cone ◽  
Holographic Microscopy ◽  
Electromagnetic Models

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.

scholarly journals Light-dependent Changes in Outer Segment Free-Ca2+ Concentration in Salamander Cone Photoreceptors

1999 ◽  
Vol 113 (2) ◽  
pp. 267-277 ◽  
Author(s):  
A.P. Sampath ◽  
H.R. Matthews ◽  
M.C. Cornwall ◽  
J. Bandarchi ◽  
G.L. Fain
Keyword(s):  
Outer Segment ◽  
Light Sensitivity ◽  
Repeated Measurements ◽  
Cone Photoreceptors ◽  
Time Constants ◽  
Background Light ◽  
Circulating Current ◽  
Simultaneous Measurements ◽  
Confocal Technique

Simultaneous measurements of photocurrent and outer segment Ca2+ were made from isolated salamander cone photoreceptors. While recording the photocurrent from the inner segment, which was drawn into a suction pipette, a laser spot confocal technique was employed to evoke fluorescence from the outer segment of a cone loaded with the Ca2+ indicator fluo-3. When a dark-adapted cone was exposed to the intense illumination of the laser, the circulating current was completely suppressed and fluo-3 fluorescence rapidly declined. In the more numerous red-sensitive cones this light-induced decay in fluo-3 fluorescence was best fitted as the sum of two decaying exponentials with time constants of 43 ± 2.4 and 640 ± 55 ms (mean ± SEM, n = 25) and unequal amplitudes: the faster component was 1.7-fold larger than the slower. In blue-sensitive cones, the decay in fluorescence was slower, with time constants of 140 ± 30 and 1,400 ± 300 ms, and nearly equal amplitudes. Calibration of fluo-3 fluorescence in situ from red-sensitive cones allowed the calculation of the free-Ca2+ concentration, yielding values of 410 ± 37 nM in the dark-adapted outer segment and 5.5 ± 2.4 nM after saturating illumination (mean ± SEM, n = 8). Photopigment bleaching by the laser resulted in a considerable reduction in light sensitivity and a maintained decrease in outer segment Ca2+ concentration. When the photopigment was regenerated by applying exogenous 11-cis-retinal, both the light sensitivity and fluo-3 fluorescence recovered rapidly to near dark-adapted levels. Regeneration of the photopigment allowed repeated measurements of fluo-3 fluorescence to be made from a single red-sensitive cone during adaptation to steady light over a range of intensities. These measurements demonstrated that the outer segment Ca2+ concentration declines in a graded manner during adaptation to background light, varying linearly with the magnitude of the circulating current.

scholarly journals Time Course and Ca2+ Dependence of Sensitivity Modulation in Cyclic Gmp-Gated Currents of Intact Cone Photoreceptors

2000 ◽  
Vol 116 (4) ◽  
pp. 521-534 ◽  
Author(s):  
Tatiana I. Rebrik ◽  
Ekaterina A. Kotelnikova ◽  
Juan I. Korenbrot
Keyword(s):  
Outer Segment ◽  
Time Course ◽  
Membrane Conductance ◽  
Cell Voltage ◽  
Mean Value ◽  
Current Amplitude ◽  
Cone Photoreceptors ◽  
First Order ◽  
Time To Peak ◽  
Pseudo First Order

We determined the Ca2+ dependence and time course of the modulation of ligand sensitivity in cGMP-gated currents of intact cone photoreceptors. In electro-permeabilized single cones isolated from striped bass, we measured outer segment current amplitude as a function of cGMP or 8Br-cGMP concentrations in the presence of various Ca2+ levels. The dependence of current amplitude on nucleotide concentration is well described by the Hill function with values of K1/2, the ligand concentration that half-saturates current, that, in turn, depend on Ca2+. K1/2 increases as Ca2+ rises, and this dependence is well described by a modified Michaelis-Menten function, indicating that modulation arises from the interaction of Ca2+ with a single site without apparent cooperativity. CaKm, the Michaelis-Menten constant for Ca2+ concentration is 857 ± 68 nM for cGMP and 863 ± 51 for 8Br-cGMP. In single cones under whole-cell voltage clamp, we simultaneously measured changes in membrane current and outer segment free Ca2+ caused by sudden Ca2+ sequestration attained by uncaging diazo-2. In the presence of constant 8Br-cGMP, 15 μΜ, Ca2+ concentration decrease was complete within 50 ms and membrane conductance was enhanced 2.33 ± 0.95-fold with a mean time to peak of 1.25 ± 0.23 s. We developed a model that assumes channel modulation is a pseudo–first-order process kinetically limited by free Ca2+. Based on the experimentally measured changes in Ca2+ concentration, model simulations match experimental data well by assigning the pseudo-first-order time constant a mean value of 0.40 ± 0.14 s. Thus, Ca2+-dependent ligand modulation occurs over the concentration range of the normal, dark-adapted cone. Its time course suggests that its functional effects are important in the recovery of the cone photoresponse to a flash of light and during the response to steps of light, when cones adapt.

scholarly journals Oncostatin M Protects Rod and Cone Photoreceptors and Promotes Regeneration of Cone Outer Segment in a Rat Model of Retinal Degeneration

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18282 ◽  
Author(s):  
Xin Xia ◽  
Yiwen Li ◽  
Deqiang Huang ◽  
Zhengying Wang ◽  
Lingyu Luo ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Rat Model ◽  
Outer Segment ◽  
Oncostatin M ◽  
Cone Photoreceptors ◽  
Rod And Cone Photoreceptors

scholarly journals Functional Characterization and Molecular Cloning of the K+-dependent Na+/Ca2+ Exchanger in Intact Retinal Cone Photoreceptors

2006 ◽  
Vol 129 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Christophe Paillart ◽  
Robert J. Winkfein ◽  
Paul P.M. Schnetkamp ◽  
Juan I. Korenbrot
Keyword(s):  
Outer Segment ◽  
Splice Variants ◽  
Functional Characterization ◽  
Cone Photoreceptors ◽  
Single Class ◽  
Rod Photoreceptors ◽  
Reverse Mode ◽  
Single Cone ◽  
Polymerase Chain ◽  
Retinal Cone

Light-dependent changes in cytoplasmic free Ca2+ are much faster in the outer segment of cone than rod photoreceptors in the vertebrate retina. In the limit, this rate is determined by the activity of an electrogenic Na+/Ca2+ exchanger located in the outer segment plasma membrane. We investigate the functional properties of the exchanger activity in intact, single cone photoreceptors isolated from striped bass retina. Exchanger function is characterized through analysis both of the electrogenic exchanger current and cytoplasmic free Ca2+ measured with optical probes. The exchanger in cones is K+ dependent and operates both in forward and reverse modes. In the reverse mode, the K+ dependence of the exchanger is described by binding to a single site with K1/2 about 3.6 mM. From the retina of the fish we cloned exchanger molecules bassNCKX1 and bassNCKX2. BassNCKX1 is a single class of molecules, homologous to exchangers previously cloned from mammalian rods. BassNCKX2 exists in four splice variants that differ from each other by small sequence differences in the single, large cytoplasmic loop characteristic of these molecules. We used RT-PCR (reverse transcriptase polymerase chain reaction) of individual cells to identify the exchanger molecule specifically expressed in bass single and twin cone photoreceptors. Each and every one of the four bassNCKX2 splice variants is expressed in both single and twin cones indistinguishably. BassNCKX1 is not expressed in cones and, by exclusion, it is likely to be an exchanger expressed in rods.

scholarly journals In Intact Cone Photoreceptors, a Ca2+-dependent, Diffusible Factor Modulates the cGMP-gated Ion Channels Differently than in Rods

1998 ◽  
Vol 112 (5) ◽  
pp. 537-548 ◽  
Author(s):  
Tatiana I. Rebrik ◽  
Juan I. Korenbrot
Keyword(s):  
Ion Channels ◽  
Outer Segment ◽  
Divalent Cations ◽  
Cone Photoreceptors ◽  
Intact Cells ◽  
Channel Modulation ◽  
Dependent Change ◽  
Diffusible Factor ◽  
The Difference ◽  
Gated Ion Channels

We investigated the modulation of cGMP-gated ion channels in single cone photoreceptors isolated from a fish retina. A new method allowed us to record currents from an intact outer segment while controlling its cytoplasmic composition by superfusion of the electropermeabilized inner segment. The sensitivity of the channels to agonists in the intact outer segment differs from that measured in membrane patches detached from the same cell. This sensitivity, measured as the ligand concentration necessary to activate half-maximal currents, K1/2, also increases as Ca2+ concentration decreases. In electropermeabilized cones, K1/2 for cGMP is 335.5 ± 64.4 μM in the presence of 20 μM Ca2+, and 84.3 ± 12.6 μM in its absence. For 8Br-cGMP, K1/2 is 72.7 ± 11.3 μM in the presence of 20 μM Ca2+ and 15.3 ± 4.5 μM in its absence. The Ca2+-dependent change in agonist sensitivity is larger in extent than that measured in rods. In electropermeabilized tiger salamander rods, K1/2 for 8Br-cGMP is 17.9 ± 3.8 μM in the presence of 20 μM Ca2+ and 7.2 ± 1.2 μM in its absence. The Ca2+-dependent modulation is reversible in intact cone outer segments, but is progressively lost in the absence of divalent cations, suggesting that it is mediated by a diffusible factor. Comparison of data in intact cells and detached membrane fragments from cones indicates that this factor is not calmodulin. At 40 μM 8Br-cGMP, the Ca2+-dependent change in sensitivity in cones is half-maximal at KCa = 286 ± 66 nM Ca2+. In rods, by contrast, KCa is ∼50 nM Ca2+. The difference in magnitude and Ca2+ dependence of channel modulation between photoreceptor types suggests that this modulation may play a more significant role in the regulation of photocurrent gain in cones than in rods.

scholarly journals Three-dimensional composition of the photoreceptor cone layers in healthy eyes using adaptive-optics optical coherence tomography (AO-OCT)

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245293
Author(s):  
Adrian Reumueller ◽  
Lorenz Wassermann ◽  
Matthias Salas ◽  
Markus Schranz ◽  
Valentin Hacker ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Adaptive Optics ◽  
Outer Segment ◽  
Three Dimensional ◽  
Optical Coherence ◽  
Cone Photoreceptors ◽  
Cone Mosaic ◽  
Automated Technique ◽  
Healthy Eyes ◽  
Cone Density

Purpose To assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT). Methods Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different planes: the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST) and full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements. Results Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC > .99). Conclusions In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology.

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