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1

Macular pigment and visual acuity in Stargardt macular dystrophy  

Microsoft Academic Search

Purpose. To test the hypothesis that macular pigment reflects foveal cone function and possibly the presence of foveal cones in recessive Stargardt macular dystrophy. Methods. Sixteen patients (32 eyes) diagnosed to have Stargardt macular dystrophy by clinical criteria were studied with a scanning laser ophthalmoscope (SLO) comparing argon laser blue (488 nm), green (514), helium-neon laser red (633 nm) and

Xinyuan Zhang; János Hargitai; Jaana Tammur; Amy Hutchinson; Rando Allikmets; Stanley Chang; Peter Gouras

2002-01-01

2

Macular pigments: their characteristics and putative role  

Microsoft Academic Search

The macular pigments (MP) absorb light in the blue-green region of the visible spectrum and comprise two carotenoids, lutein and zeaxanthin. In humans the concentration of MP varies widely across the normal population. There are two (not mutually exclusive) proposed roles for MP: to improve visual function and to act as an antioxidant and protect the macula from damage by

Nigel P. Davies; Antony B. Morland

3

Macular Pigment and Its Contribution to Vision  

PubMed Central

Three dietary carotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the central retina (macula), where they are collectively referred to as macular pigment (MP). MP’s pre-receptoral absorption of blue light and consequential attenuation of the effects of chromatic aberration and light scatter are important for optimal visual function. Furthermore, antioxidant activity of MP’s constituent carotenoids and the same blue light-filtering properties underlie the rationale for its putative protective role for age-related macular degeneration (AMD). Supplementation with L, Z and MZ augments MP and enhances visual performance in diseased and non-diseased eyes, and may reduce risk of AMD development and/or progression. PMID:23760061

Loskutova, Ekaterina; Nolan, John; Howard, Alan; Beatty, Stephen

2013-01-01

4

Macular pigment optical density in a midwestern sample  

Microsoft Academic Search

ObjectiveTo assess the distribution of the macular pigments (MPs) lutein (L) and zeaxanthin (Z) in a healthy sample more representative of the general population than past studies and to determine which dietary factors and personal characteristics might explain the large interindividual differences in the density of these MPs.

Thomas A Ciulla; Joanne Curran-Celantano; Dale A Cooper; Billy R Hammond; Ronald P Danis; Linda M Pratt; Karen A Riccardi; Thomas G Filloon

2001-01-01

5

A One Year Study of the Macular Pigment: The Effect of 140 Days of a Lutein Supplement  

Microsoft Academic Search

A low density of macular pigment may represent a risk factor for age-related macular degeneration (AMD) by permitting greater blue light damage. This study was carried out to determine the effects on macular pigment optical density of dietary supplementation with lutein, one of the pigment constituents. Two subjects consumed lutein esters, equivalent to 30 mg of free lutein per day,

JOHN T LANDRUM; RICHARD A BONE; HILDA JOA; MARK D KILBURN; LINDA L MOORE; KATHLEEN E SPRAGUE

1997-01-01

6

Two-wavelength fundus autofluorescence and macular pigment optical density imaging in diabetic macular oedema  

PubMed Central

Purpose To evaluate the application of 488 and 514?nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features. Patients and Methods A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514?nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference. Results Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488?nm FAF, 0.63 for 514?nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488?nm FAF; 55.2 and 94.8% for 514?nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488?nm FAF and MPOD imaging, DMO was better visualised in comparison with 514?nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts. Conclusion MPOD imaging, and particularly its combination with 488?nm and 514?nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula. PMID:22699976

Waldstein, S M; Hickey, D; Mahmud, I; Kiire, C A; Charbel Issa, P; Chong, N V

2012-01-01

7

Macular Pigment Optical Density Measured by Heterochromatic Modulation Photometry  

PubMed Central

Purpose To psychophysically determine macular pigment optical density (MPOD) employing the heterochromatic modulation photometry (HMP) paradigm by estimating 460 nm absorption at central and peripheral retinal locations. Methods For the HMP measurements, two lights (B: 460 nm and R: 660 nm) were presented in a test field and were modulated in counterphase at medium or high frequencies. The contrasts of the two lights were varied in tandem to determine flicker detection thresholds. Detection thresholds were measured for different R:B modulation ratios. The modulation ratio with minimal sensitivity (maximal threshold) is the point of equiluminance. Measurements were performed in 25 normal subjects (11 male, 14 female; age: 30±11 years, mean ± sd) using an eight channel LED stimulator with Maxwellian view optics. The results were compared with those from two published techniques – one based on heterochromatic flicker photometry (Macular Densitometer) and the other on fundus reflectometry (MPR). Results We were able to estimate MPOD with HMP using a modified theoretical model that was fitted to the HMP data. The resultant MPODHMP values correlated significantly with the MPODMPR values and with the MPODHFP values obtained at 0.25° and 0.5° retinal eccentricity. Conclusions HMP is a flicker-based method with measurements taken at a constant mean chromaticity and luminance. The data can be well fit by a model that allows all data points to contribute to the photometric equality estimate. Therefore, we think that HMP may be a useful method for MPOD measurements, in basic and clinical vision experiments. PMID:25354049

Huchzermeyer, Cord; Schlomberg, Juliane; Welge-Lüssen, Ulrich; Berendschot, Tos T. J. M.; Pokorny, Joel; Kremers, Jan

2014-01-01

8

Staging of Macular Telangiectasia: Power-Doppler Optical Coherence Tomography and Macular Pigment Optical Density  

PubMed Central

Purpose. Two methods were used to study the stages of macular telangiectasia (MacTel): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. Methods. Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. Results. Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. Conclusions. PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel. PMID:23716628

Chin, Eric K.; Kim, Dae Yu; Hunter, Allan A.; Pilli, Suman; Wilson, Machelle; Zawadzki, Robert J.; Werner, John S.; Park, Susanna S.

2013-01-01

9

Measuring macular pigment optical density in vivo: a review of techniques  

Microsoft Academic Search

Background  Macular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related\\u000a macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in\\u000a vivo.\\u000a \\u000a \\u000a \\u000a \\u000a Method  A systematic literature search was undertaken to identify all available papers that have used in vivo MPOD techniques. The\\u000a papers were

Olivia Howells; Frank Eperjesi; Hannah Bartlett

2011-01-01

10

Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study  

Microsoft Academic Search

BACKGROUNDSubthreshold (retinal pigment epithelium) photocoagulation is a new photocoagulation method, which treats the retinal pigment epithelium (RPE) and avoids damage to the neural retina. The initial results in this prospective pilot study on various macular diseases are presented.METHODS12 patients with diabetic maculopathy (group I), 10 with soft drusen (group II), and four with central serous retinopathy (CSR) (group III) were

Johann Roider; Ralf Brinkmann; Christopher Wirbelauer; Horst Laqua; Reginald Birngruber

2000-01-01

11

Bimodal spatial distribution of macular pigment: evidence of a gender relationship  

NASA Astrophysics Data System (ADS)

The spatial distribution of the optical density of the human macular pigment measured by two-wavelength autofluorescence imaging exhibits in over half of the subjects an annulus of higher density superimposed on a central exponential-like distribution. This annulus is located at about 0.7° from the fovea. Women have broader distributions than men, and they are more likely to exhibit this bimodal distribution. Maxwell's spot reported by subjects matches the measured distribution of their pigment. Evidence that the shape of the foveal depression may be gender related leads us to hypothesize that differences in macular pigment distribution are related to anatomical differences in the shape of the foveal depression.

Delori, François C.; Goger, Douglas G.; Keilhauer, Claudia; Salvetti, Paola; Staurenghi, Giovanni

2006-03-01

12

Studies on the Singlet Oxygen Scavenging Mechanism of Human Macular Pigment  

PubMed Central

It is thought that direct quenching of singlet oxygen and scavenging free radicals by macular pigment carotenoids is a major mechanism for their beneficial effects against light-induced oxidative stress. Corresponding data from human tissue remains unavailable, however. In the studies reported here, electron paramagnetic resonance (EPR) spectroscopy was used to measure light-induced singlet oxygen generation in postmortem human macula and retinal pigment epithelium/choroid (RPE/choroid). Under white-light illumination, production of singlet oxygen was detected in RPE/choroid but not in macular tissue, and we show that exogenously added macular carotenoids can quench RPE/choroid singlet oxygen. When the singlet oxygen quenching ability of the macular carotenoids was investigated in solution, it was shown that a mixture of meso-zeaxanthin, zeaxanthin, and lutein in a ratio of 1:1:1 can quench more singlet oxygen than the individual carotenoids at the same total concentration. PMID:20678467

Li, Binxing; Ahmed, Faisal; Bernstein, Paul S.

2010-01-01

13

Macular translocation with 360° retinotomy for management of retinal pigment epithelial tear: long-term results  

Microsoft Academic Search

BackgroundTo determine long-term functional and morphological changes after full macular translocation (FMT) with 360° retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF)-modulating therapy.MethodsWe retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent

A. Polito; M. Cereda; F. Romanelli; G. Pertile

2010-01-01

14

Macular pigment optical density spatial distribution measured in a subject with oculocutaneous albinism  

PubMed Central

Purpose Previous studies of macular pigment optical density (MPOD) distribution in individuals with oculocutaneous albinism (OCA) have primarily used objective measurement techniques including fundus reflectometry and autofluorescence. We report here on a subject with OCA and their corresponding MPOD distribution assessed through heterochromatic flicker photometry (HFP). Methods A subject with a history of OCA presented with an ocular history including strabismus surgery of the LE with persistent amblyopia and mild, latent nystagmus. Best corrected visual acuity was 20/25- RE and 20/40- LE. Spectral domain optical coherence tomography (SD-OCT) and fundus photography were also obtained. Evaluation of MPOD spatial distribution up to 8 degrees eccentricity from the fovea was performed using HFP. Results SD-OCT indicated a persistence of multiple inner retinal layers within the foveal region in the RE and LE including symmetric foveal thickening consistent with foveal hypoplasia. Fundus photography showed mild retinal pigmented epithelial (RPE) hypopigmentation and a poorly demarcated macula. OriginPro 9 was used to plot MPOD spatial distribution of the subject and a 33-subject sample. The OCA subject demonstrated a foveal MPOD of 0.10 with undetectable levels at 6 degrees eccentricity. The study sample showed a mean foveal MPOD of 0.34 and mean 6 degree eccentricity values of 0.03. Conclusions Consistent with previous macular pigment (MP) studies of OCA, overall MPOD is reduced in our subject. Mild phenotypic expression of OCA with high functional visual acuity may represent a Henle fiber layer amenable to additional MP deposition. Further study of MP supplementation in OCA patients is warranted. PMID:25323647

Putnam, Christopher M.; Bland, Pauline J.

2014-01-01

15

The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation, inflammation and oxidation: pilot studies in healthy volunteers.  

PubMed

The aim of the present study was to compare the effect of lutein- and zeaxanthin-rich foods and supplements on macular pigment level (MPL) and serological markers of endothelial activation, inflammation and oxidation in healthy volunteers. We conducted two 8-week intervention studies. Study 1 (n 52) subjects were randomised to receive either carrot juice (a carotene-rich food) or spinach powder (a lutein- and zeaxanthin-rich food) for 8 weeks. Study 2 subjects (n 75) received supplements containing lutein and zeaxanthin, ?-carotene, or placebo for 8 weeks in a randomised, double-blind, placebo-controlled trial. MPL, serum concentrations of lipid-soluble antioxidants, inter-cellular adhesion molecule 1, vascular cell adhesion molecule 1, C-reactive protein and F2-isoprostane levels were assessed at baseline and post-intervention in both studies. In these intervention studies, no effects on MPL or markers of endothelial activation, inflammation or oxidation were observed. However, the change in serum lutein and zeaxanthin was associated or tended to be associated with the change in MPL in those receiving lutein- and zeaxanthin-rich foods (lutein r 0.40, P = 0.05; zeaxanthin r 0.30, P = 0.14) or the lutein and zeaxanthin supplement (lutein r 0.43, P = 0.03; zeaxanthin r 0.22, P = 0.28). In both studies, the change in MPL was associated with baseline MPL (food study r - 0.54, P < 0.001; supplement study r - 0.40, P < 0.001). We conclude that this 8-week supplementation with lutein and zeaxanthin, whether as foods or as supplements, had no significant effect on MPL or serological markers of endothelial activation, inflammation and oxidation in healthy volunteers, but may improve MPL in the highest serum responders and in those with initially low MPL. PMID:22313522

Graydon, Ryan; Hogg, Ruth E; Chakravarthy, Usha; Young, Ian S; Woodside, Jayne V

2012-07-01

16

Full-thickness macular hole formation associated with pigment epithelial detachment: link or coincidence?  

PubMed

To report two cases of full-thickness macular hole (FTMH) formation associated with pigment epithelial detachment (PED). Two patients presenting with visual loss and metamorphopsia were evaluated with fundal fluorescein angiography (FFA) and optical coherence tomography (OCT). Case 1: Fundus examination and FFA revealed a small subfoveal PED. Subsequent serial OCT elucidated the progressive formation of a FTMH. Case 2: Fundus examination and FFA revealed a small PED and changes suggestive of central serous retinopathy (CSR). Subsequent OCT illustrated a FTMH with an underlying small PED at the base of the hole. It is possible that, in at least some cases of macular hole formation, there may be a causative link with PED. To my knowledge, this is the first report of full-thickness macular hole formation associated with pigment epithelial detachment. PMID:20517636

Cazabon, Sunildath

2010-12-01

17

N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have ele- vated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochon- dria, disruption of retinal metabolism, and vision impair- ment or loss. As a possible model for iron-induced AMD, we investigated

Ludmila A. Voloboueva; David W. Killilea; Hani Atamna; Bruce N. Ames

2007-01-01

18

Influence of macular pigment and melanin on incident early AMD in a white population  

Microsoft Academic Search

Background  The protective effect of macular pigment (MP) and melanin against age-related macular degeneration (AMD) is still controversial\\u000a from cross-sectional studies. In an attempt to clarify this issue, we performed a population-based longitudinal study.\\u000a \\u000a \\u000a \\u000a Methods  MP optical density (MPOD) and melanin optical density (MOD) data were collected during the second follow-up phase of the Rotterdam\\u000a Study in 1999 in a random subset

Martijn J. Kanis; Tos T. J. M. Berendschot; Dirk van Norren

2007-01-01

19

Autofluorescence imaging of macular pigment: influence and correction of ocular media opacities.  

PubMed

The healthy adult human retina contains in its macular region a high concentration of blue-light absorbing carotenoid compounds, known as macular pigment (MP). Consisting of the carotenoids lutein, zeaxanthin, and meso-zeaxanthin, the MP is thought to shield the vulnerable tissue layers in the retina from lightinduced damage through its function as an optical attenuator and to protect the tissue cells within its immediate vicinity through its function as a potent antioxidant. Autofluorescence imaging (AFI) is emerging as a viable optical method for MP screening of large subject populations, for tracking of MP changes over time, and for monitoring MP uptake in response to dietary supplementation. To investigate the influence of ocular media opacities on AFI-based MP measurements, in particular, the influence of lens cataracts, we conducted a clinical trial with a large subject population (93 subjects) measured before and after cataract surgery. General AFI image contrast, retinal blood vessel contrast, and presurgery lens opacity scores [Lens Opacities Classification System III (LOCS III)] were investigated as potential predictors for image degradation. These clinical results show that lens cataracts can severely degrade the achievable pixel contrasts in the AFI images, which results in nominal MP optical density levels that are artifactually reduced. While LOCS III scores and blood vessel contrast are found to be only a weak predictor for this effect, a strong correlation exists between the reduction factor and the image contrast, which can be quantified via pixel intensity histogram parameters. Choosing the base width of the histogram, the presence or absence of ocular media opacities can be determined and, if needed, the nominal MP levels can be corrected with factors depending on the strength of the opacity. PMID:25223707

Sharifzadeh, Mohsen; Obana, Akira; Gohto, Yuko; Seto, Takahiko; Gellermann, Werner

2014-09-01

20

Light Distributions on the Retina: Relevance to Macular Pigment Photoprotection  

PubMed Central

Light exposure has been implicated in age-related macular degeneration (AMD). This study was designed to measure cumulative light distribution on the retina to determine whether it peaked in the macula. An eye-tracker recorded the subject's field of view and pupil size, and superimposed the gaze position. Fifteen naïve subjects formed a test group; 5 formed a control group. In phase 1, all subjects viewed a sequence of photographic images. In phase 2, the naïve subjects observed a video; in phase 3, they performed computer tasks; in phase 4, the subjects walked around freely. In phase 1, control subjects were instructed to gaze at bright features in the field of view and, in a second test, at dark features. Test group subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, we calculated the cumulative light distribution on the retina. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark features respectively in the field of view. The light distribution maps obtained from the test group showed a consistent tendency to peak in the macula in phase 3, a variable tendency in phase 4, but little tendency in phases 1 and 2. We conclude that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased but, at the same time, mitigated by the presence of macular carotenoids. PMID:22428119

Bone, Richard A.; Gibert, Jorge C.; Mukherjee, Anirbaan

2012-01-01

21

Prevalence and Progression of Pigment Clumping Associated with Idiopathic Macular Telangiectasia Type 2 (IMT2)  

PubMed Central

Purpose To investigate pigment clumping in idiopathic macular telangiectasia type 2 (IMT2) for its incidence, development, and progression during the course of the disease. Methods Patients with a diagnosis of IMT2 and greater than 12 months of follow-up were reviewed retrospectively. Measurements of the area of pigment clumping were performed and correlated with visual acuity and findings on spectral domain optical coherence tomography (OCT) and microperimetry (MP1). Results Fifty-three eyes in 27 patients with a mean follow-up of 42.5±14.2 months (range 12–79 months) were included. At study baseline, 16 eyes (30%) had evidence of pigment clumping without associated neovascular changes. During follow-up, 8/33 (24%) additional study eyes without prior pigment clumping developed it in stage 3 (Gass-Blodi classification) disease. Pigment clumping increased in overall area as a function of follow-up time. Pigment clumping was associated with increased intraretinal reflectivity on OCT and development of scotomas on microperimetry. Conclusions Pigment clumping commonly develops in stage 3 IMT2 disease, enlarges in area continuously over time, and is associated with declining visual function. Longitudinal measurements of the total area of pigment clumping may be helpful in following disease progression and may constitute a useful outcome measure for interventional clinical studies. PMID:23064429

Meleth, Annal D.; Toy, Brian C.; Nigam, Divya; Agron, Elvira; Murphy, Robert P.; Chew, Emily Y.; Wong, Wai T.

2012-01-01

22

Lutein and zeaxanthin: Role as macular pigment and factors that control bioavailability from egg yolks and nanoemulsions  

Microsoft Academic Search

Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from damaging blue radiation of sunlight. As macular pigment, lutein and zeaxanthin are also potent antioxidants protecting the vulnerable regions of retina from free radical injury. Oxidative stress and cumulative light damage play an important role in pathogenesis of age-related

Rohini Vishwanathan

2010-01-01

23

Decreased membrane complement regulators in the retinal pigmented epithelium contributes to age-related macular degeneration.  

PubMed

Dysregulated complement is thought to play a central role in age-related macular degeneration (AMD) pathogenesis, but the specific mechanisms have yet to be determined. In maculae of AMD specimens, we found that the complement regulatory protein, CD59, was increased in regions of uninvolved retinal pigmented epithelium (RPE) of early AMD, but decreased in the RPE overlying drusen and in geographic atrophy, an advanced form of AMD. While CD46 immunostaining was basolaterally distributed in the RPE of unaffected controls, it was decreased in diseased areas of early AMD samples. Since oxidized low-density lipoproteins (oxLDL) collect in drusen of AMD and are a known complement trigger, we treated ARPE-19 cells with oxLDL and found that cellular CD46 and CD59 proteins were decreased by 2.9- and nine-fold (p < 0.01), respectively. OxLDLs increased complement factor B mRNA and Bb protein, but not factor D, I or H. OxLDLs increased C3b, but not C3a, C5 or C5b-9. C5b-9 was increased by 27% (p < 0.01) when the medium was supplemented with human serum, which was sufficient to induce poly(ADP-ribose) polymerase cleavage, a marker of apoptosis. The decreased levels of CD46 and CD59 were in part explained by their release in exosomal and apoptotic membranous particles. In addition, CD59 was partially degraded through activation of IRE1?. Collectively, these results suggest that a combination of impaired complement regulators results in inadequately controlled complement by the RPE in AMD that induces RPE damage. PMID:23097248

Ebrahimi, Katayoon B; Fijalkowski, Natalia; Cano, Marisol; Handa, James T

2013-04-01

24

Heritability of the spatial distribution and peak density of macular pigment: a classical twin study  

PubMed Central

Purpose To elucidate the heritability of peak density and spatial width of macular pigment (MP) using a Classical Twin Study. Methods Fundus autofluorescence images were obtained at 488?nm from 86 subjects or 43 twin pairs (21 monozygotic (MZ) and 22 dizygotic (DZ)) (27 male, 59 female) aged from 55 to 76 years (mean 62.2±5.3 years). The relative topographic distribution of MP was measured using a grey scale of intensity (0–255 units) in a 7° eccentricity around the fovea. Relative peak MP density (rPMPD) and relative spatial distribution of MP (rSDMP) were used as the main outcome measure in the statistical analysis. Results A significantly higher correlation was found within MZ pairs as compared with that within DZ pairs for rPMPD, (r=0.99, 95% confidence interval (95% CI) 0.93 to 1.00) and 0.22, 95% CI ?0.34 to 0.71), respectively, suggesting strong heritability of this trait. When rSDMP was compared, there was no significant difference between the correlations within MZ pairs (r=0.48, 95% CI ?0.02 to 0.83) and DZ pairs (r=0.63, 95% CI 0.32 to 0.83), thus rSDMP is unlikely to have a considerable heritable component. In addition, there was no difference between any MP parameter when normal maculae were compared with early age-related macular degeneration (AMD) (rPMPD 0.36 vs 0.34, t=1.18 P=0.243, rSDMP 1.75 vs 1.75, t=0.028 P=0.977). Conclusions rPMPD is a strongly heritable trait whereas rSDMP has minimal genetic influence and a greater influence by environmental factors. The presence of macular changes associated with early AMD did not appear to influence any of these pigment parameters. PMID:22744384

Hogg, R E; Ong, E L; Chamberlain, M; Dirani, M; Baird, P N; Guymer, R H; Fitzke, F

2012-01-01

25

SOD2 Protects against Oxidation-Induced Apoptosis in Mouse Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration  

Microsoft Academic Search

PURPOSE. Oxidative stress from reactive oxygen species (ROS) has been implicated in many diseases, including age-related macular degeneration (AMD), in which the retinal pigment epithelium (RPE) is considered a primary target. Because man- ganese superoxide dismutase (SOD2), localized in mitochon- dria, is known to be a key enzyme that protects the cells against oxidative stress, this study was undertaken to

Emiko Kasahara; Li-Ren Lin; Ye-Shih Ho; Venkat N. Reddy

2005-01-01

26

Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults.  

PubMed

Low carotenoid status (especially of the xanthophylls, lutein [L], and zeaxanthin [Z]) is common in older adults and has been associated with a number of degenerative diseases of the central nervous system ranging from retina (e.g., macular degeneration) to brain (e.g., Alzheimer's disease). In this study, we tested whether retinal measures of L + Z (macular pigment optical density [MPOD]), used as a surrogate for brain L + Z levels, were related to cognitive function when comparing healthy older adults with mildly cognitively impaired older adults. Twenty-four subjects with mild cognitive impairment were compared with 24 matched controls. Subjects were matched with respect to age, body mass index, ethnicity, sex, and smoking status. Degree of cognitive impairment and cognitive ability was determined via structured clinical interview. MPOD was measured psychophysically. In healthy older adults, MPOD was only related to visual-spatial and constructional abilities (p = 0.04). For subjects with mild cognitive impairment (MCI), however, MPOD was broadly related to cognition including the composite score on the mini-mental state examination (p = 0.02), visual-spatial and constructional abilities (p = 0.04), language ability (p = 0.05), attention (p = 0.03), and the total scale on the Repeatable Battery for the Assessment of Neuropsychological Status (p = 0.03). It is possible that L/Z status may be more strongly related to cognition when individuals are considered with established onset of cognitive decline. PMID:24508218

Renzi, Lisa M; Dengler, Melissa J; Puente, Antonio; Miller, L Stephen; Hammond, Billy R

2014-07-01

27

Black tongue secondary to bismuth subsalicylate: case report and review of exogenous causes of macular lingual pigmentation.  

PubMed

Macular pigmentation of the tongue can be acquired following exposure to exogenous agents. Black lingual hyperpigmentation was observed during the full body skin examination of a man with a history of recurrent metastatic malignant melanoma. His tongue spontaneously returned to its normal pink color later that day. Bismuth subsalicylate (Pepto-Bismol) was suspected as the pigment-inducing agent; subsequently, re-challange with the antacid confirmed it to be the cause of his acquired, albeit transient, black tongue. The ingestion of medications, including other antacids, analgesics, antidepressants, antihypertensives and several antimicrobials has been associated with the development of acquired macular lingual pigmentation. In addition, hyperpigmentation of the tongue has been observed following the deposition of amalgam and the injection of local anesthesia or doxorubicin or interferon alpha and ribavirin. Also, inhalation of heroin and methaqualone vapors or tobacco has resulted in lingual hyperpigmentation. All of the patients with acquired macular lingual hyperpigmentation had tongues with a smooth surface without enlargement of the filiform papillae. Many of the individuals with hyperpigmented tongue had either black or dark skin color. The onset of tongue pigmentation varied from less than one day to several years after initial exposure to the associated exogenous agent. The color of the tongue usually returned to normal after the pigment-inducing agent was discontinued. PMID:20027942

Cohen, Philip R

2009-12-01

28

Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization-sensitive optical coherence tomography.  

PubMed

Purpose. Spectral-domain optical coherence tomography (SD-OCT) provides new insights into the understanding of age-related macular degeneration (AMD) but limited information on the nature of hyperreflective tissue at the level of the retinal pigment epithelium. Therefore, polarization-sensitive (PS) SD-OCT was used to identify and characterize typical RPE findings in AMD. Methods. Forty-four eyes of 44 patients with AMD were included in this prospective case series representing the entire AMD spectrum from drusen (n = 11), geographic atrophy (GA; n = 11), neovascular AMD (nAMD; n = 11) to fibrotic scars (n = 11). Imaging systems were used for comparative imaging. A PS-SD-OCT instrument was developed that was capable of recording intensity and polarization parameters simultaneously during a single scan. Results. In drusen, PS-SD-OCT identified a continuous RPE layer with focal elevations. Discrete RPE atrophy (RA) could be observed in two patients. In GA, the extension of the RA was significantly larger. Residual RPE islands could be detected within the atrophic zone. PS-SD-OCT identified multiple foci of RPE loss in patients with nAMD and allowed recognition of advanced RPE disease associated with choroidal neovascularization. Wide areas of RA containing residual spots of intact retinal pigment epithelium could be identified in fibrotic scars. Conclusions. PS-SD-OCT provided precise identification of retinal pigment epithelium in AMD. Recognition of these disease-specific RA patterns in dry and wet forms of AMD is of particular relevance to identify the status and progression of RPE disease and may help to better estimate the functional prognosis of AMD. PMID:19797228

Ahlers, Christian; Götzinger, Erich; Pircher, Michael; Golbaz, Isabelle; Prager, Franz; Schütze, Christopher; Baumann, Bernhard; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

2010-04-01

29

Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration.  

PubMed

Age-related macular degeneration (AMD) is a sight threating retinal eye disease that affects millions of aging individuals world-wide. Choroid-retinal pigment epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the primary site of AMD pathology. There are compelling evidence to indicate association of vascular endothelial growth factors (VEGF) to AMD. Here, we report the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-? and hypoxia induced VEGF secretion by human retinal pigment epithelial cells (HRPE). HRPE cultures prepared from aged human donor eyes were used for the studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-?, TNF-?, IL-1?), significantly increased the secretion of both VEGF-A and VEGF-C. RSV, in a dose dependent (10-50 uM) manner, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines significantly. RT-PCR analysis indicated that effects of RSV on VEGF secretion were possibly due to decreased mRNA levels. TGF-? and cobalt chloride (hypoxia mimic) also upregulated HRPE cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no effect on anti-angiogenic molecules, endostatin and pigment epithelial derived factor secretion. Studies using an in vitro scratch assay revealed that wound closure was also inhibited by RSV. These results demonstrate that RSV can suppress VEGF secretion induced by inflammatory cytokines, TGF-? and hypoxia. Under pathological conditions, over expression of VEGF is known to worsen AMD. Therefore, RSV may be useful as nutraceutical in controlling pathological choroidal neovascularization processes in AMD. PMID:24729934

Nagineni, Chandrasekharam N; Raju, Raghavan; Nagineni, Krishnasai K; Kommineni, Vijay K; Cherukuri, Aswini; Kutty, R Krishnan; Hooks, John J; Detrick, Barbara

2014-04-01

30

Simple and objective method for routine detection of the macular pigment xanthophyll  

NASA Astrophysics Data System (ADS)

A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R2 = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491+/-0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615+/-0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610+/-0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674+/-0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.

Schweitzer, Dietrich; Jentsch, Susanne; Dawczynski, Jens; Hammer, Martin; Wolf-Schnurrbusch, Ute E. K.; Wolf, Sebastian

2010-11-01

31

Recovery of macular pigment spectrum in vivo using hyperspectral image analysis  

PubMed Central

We investigated the feasibility of a novel method for hyperspectral mapping of macular pigment (MP) in vivo. Six healthy subjects were recruited for noninvasive imaging using a snapshot hyperspectral system. The three-dimensional full spatial-spectral data cube was analyzed using non-negative matrix factorization (NMF), wherein the data was decomposed to give spectral signatures and spatial distribution, in search for the MP absorbance spectrum. The NMF was initialized with the in vitro MP spectrum and rank 4 spectral signature decomposition was used to recover the MP spectrum and optical density in vivo. The recovered MP spectra showed two peaks in the blue spectrum, characteristic of MP, giving a detailed in vivo demonstration of these absorbance peaks. The peak MP optical densities ranged from 0.08 to 0.22 (mean 0.15+/?0.05) and became spatially negligible at diameters 1100 to 1760 ?m (4 to 6 deg) in the normal subjects. This objective method was able to exploit prior knowledge (the in vitro MP spectrum) in order to extract an accurate in vivo spectral analysis and full MP spatial profile, while separating the MP spectra from other ocular absorbers. Snapshot hyperspectral imaging in combination with advanced mathematical analysis provides a simple cost-effective approach for MP mapping in vivo. PMID:22029355

Fawzi, Amani A.; Lee, Noah; Acton, Jennifer H.; Laine, Andrew F.; Smith, R. Theodore

2011-01-01

32

Recovery of macular pigment spectrum in vivo using hyperspectral image analysis.  

PubMed

We investigated the feasibility of a novel method for hyperspectral mapping of macular pigment (MP) in vivo. Six healthy subjects were recruited for noninvasive imaging using a snapshot hyperspectral system. The three-dimensional full spatial-spectral data cube was analyzed using non-negative matrix factorization (NMF), wherein the data was decomposed to give spectral signatures and spatial distribution, in search for the MP absorbance spectrum. The NMF was initialized with the in vitro MP spectrum and rank 4 spectral signature decomposition was used to recover the MP spectrum and optical density in vivo. The recovered MP spectra showed two peaks in the blue spectrum, characteristic of MP, giving a detailed in vivo demonstration of these absorbance peaks. The peak MP optical densities ranged from 0.08 to 0.22 (mean 0.15+?-0.05) and became spatially negligible at diameters 1100 to 1760 ?m (4 to 6 deg) in the normal subjects. This objective method was able to exploit prior knowledge (the in vitro MP spectrum) in order to extract an accurate in vivo spectral analysis and full MP spatial profile, while separating the MP spectra from other ocular absorbers. Snapshot hyperspectral imaging in combination with advanced mathematical analysis provides a simple cost-effective approach for MP mapping in vivo. PMID:22029355

Fawzi, Amani A; Lee, Noah; Acton, Jennifer H; Laine, Andrew F; Smith, R Theodore

2011-10-01

33

Markers of lutein and zeaxanthin status in two age groups of men and women: dietary intake, serum concentrations, lipid profile and macular pigment optical density  

PubMed Central

Background & aims Lutein and zeaxanthin accumulate in retina (macular pigment). Their nutritional status can be assessed using dietary or biochemical markers and both have been associated with macular pigment optical density. We proposed to assess dietary and status markers of lutein and zeaxanthin in a group of healthy Spanish volunteers, considering the potential influence of age, gender and serum lipids to investigate the predictors of the macular pigment optical density. Methods Serum lutein and zeaxanthin concentrations, dietary intake and macular pigment optical density were determined in 108 healthy men and women (20–35 and 45–65 years), using high-performance liquid chromatography, 3-day food records and heterochromic flicker photometry, respectively. Mann–Whitney U-test, Spearman correlation coefficient and multivariate regression analysis were used for the statistical study. Results Serum concentrations and dietary intake of lutein plus zeaxanthin (p?macular pigment optical density was lower (p?=?0.038). The highest correlation coefficients between intake and serum were for fruit and serum lutein (??=?0.452, p?Macular pigment optical density correlated with serum xanthophylls (??=?0.223, p?=?0.02) and fruit and vegetable intake (??=?0.350, p?=?0.0002), showing highest correlations when lutein and zeaxanthin were expressed in relation to serum lipids in older subjects (??=?0.262, p?=?0.006). Multivariate regression analysis identified age and serum lutein as major predictors of macular pigment optical density (total sample), and a coefficient of determination of 29.7% for the model including lutein?+?zeaxathin/cholesterol?+?triglycerides, sex and fruit?+?vegetables in the older group. Conclusions The establishment of normal/reference ranges for serum lutein and zeaxanthin should consider age ranges and be expressed in relation to lipid concentrations, at least in subjects over 45 years, as this could influence macular pigment optical density. The macular pigment optical density showed age-specific correlations with lutein plus zeaxanthin expressed in relation to serum lipid concentrations as well as with the fruit and vegetable intake. PMID:24889185

2014-01-01

34

Formation and progression of sub-retinal pigment epithelium deposits in Efemp1 mutation knock-in mice: a model for the early pathogenic course of macular degeneration  

Microsoft Academic Search

Malattia leventinese (ML) is a dominantly inherited macular degenerative disease characterized by the presence of sub-retinal pigment epithelium (RPE) deposits. With the exception of an earlier age of onset, ML patients exhibit symptoms and histopathology compatible with the diagnosis of age-related macular degeneration (AMD), the most common cause of incurable blindness. ML is caused by a mutation (R345W) in the

Lihua Y. Marmorstein; Precious J. McLaughlin; Neal S. Peachey; Takako Sasaki; Alan D. Marmorstein

2007-01-01

35

Progressive atrophy of retinal pigment epithelium after trypan-blue-assisted ILM peeling for macular hole surgery  

PubMed Central

We report a case of progressive atrophy of the retinal pigment epithelium (RPE) after trypan-blue-assisted peeling of internal limiting membrane (ILM) for macular hole surgery. A 68-year-old Caucasian female underwent a 20-g pars plana vitrectomy for a chronic stage-3 macular hole. The ILM was stained with 0.06% trypan blue (VisionBlue™, DORC Netherlands) for 2 min after fluid air exchange. Dye was reapplied for another 2 min due to poor staining. The ILM was completely removed around the macular hole with forceps. RPE atrophy was noticed at the edge of the hole 1 month after surgery. It progressively increased in intensity and enlarged over 2 years. Her final visual acuity was counting fingers, significantly worse compared to her presenting visual acuity of 20/200. Progressive atrophy of RPE in our patient was most likely due to the toxicity of trypan blue. Reapplication of the dye may increase the likelihood of toxicity. PMID:23619488

Jain, Sachin; Kishore, Kamal; Sharma, Yog Raj

2013-01-01

36

Resonance Raman Measurement of Macular Carotenoids in Retinal, Choroidal, and Macular Dystrophies  

Microsoft Academic Search

Background: It has been hypothesized that the macu- lar carotenoid pigments lutein and zeaxanthin may pro- tect against macular and retinal degenerations and dys- trophies. Objective: To test this hypothesis by objectively mea- suring lutein and zeaxanthin levels in a noninvasive man- ner in patients who have retinitis pigmentosa (RP), cho- roideremia (CHM), and Stargardt macular dystrophy and comparing them

Da-You Zhao; Steven W. Wintch; Igor V. Ermakov; Werner Gellermann; Paul S. Bernstein

2003-01-01

37

Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes  

Microsoft Academic Search

BACKGROUNDIt has been suggested that eating green leafy vegetables, which are rich in lutein and zeaxanthin, may decrease the risk for age related macular degeneration. The goal of this study was to analyse various fruits and vegetables to establish which ones contain lutein and\\/or zeaxanthin and can serve as possible dietary supplements for these carotenoids.METHODSHomogenates of 33 fruits and vegetables,

Olaf Sommerburg; Jan E E Keunen; Alan C Bird; Frederik J G M van Kuijk

1998-01-01

38

Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD. PMID:23590900

Sinha, Debasish; Blasiak, Janusz; Kauppinen, Anu; Vereb, Zoltan; Salminen, Antero; Boulton, Michael E.; Petrovski, Goran

2013-01-01

39

Imaging system to assess objectively the optical density of the macular pigment in vivo  

E-print Network

of the technique employed and the solutions implemented in the MacPI system to confront those inherent frailties]. Wald established that the pigment absorbed light between the wavelengths 430 and 490 nm, with maximum

Dainty, Chris

40

Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration  

Microsoft Academic Search

PurposeThere is evidence for complement dysfunction in age-related macular degeneration (AMD). Complement activation leads to formation of the membrane attack complex (MAC), known to assemble on retinal pigment epithelial (RPE) cells. Therefore, the effect of sub-lytic MAC on RPE cells was examined with regard to pro-inflammatory or pro-angiogenic mediators relevant in AMD.MethodsFor sub-lytic MAC induction, RPE cells were incubated with

K Lueck; S Wasmuth; J Williams; T R Hughes; B P Morgan; A Lommatzsch; J Greenwood; S E Moss; D Pauleikhoff

2011-01-01

41

Patterns of increased in vivo fundus autofluorescence in the junctional zone of geographic atrophy of the retinal pigment epithelium associated with age-related macular degeneration  

Microsoft Academic Search

Purpose: To determine in vivo lipofuscin (LF)-induced topographic variations of fundus autofluorescence in eyes with geographic\\u000a atrophy (GA) of the retinal pigment epithelium (RPE) associated with age-related macular degeneration (ARMD).? Methods: Fundus autofluorescence was examined with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph)\\u000a after excitation with an argon laser (488 nm) and detection of the emitted light above 500

Frank G. Holz; Caren Bellmann; Melenaos Margaritidis; Florian Schütt; Tilman P. Otto; Hans E. Völcker

1999-01-01

42

Effect of ranibizumab on serous and vascular pigment epithelial detachments associated with exudative age-related macular degeneration  

PubMed Central

Purpose To report the effect of intravitreal ranibizumab therapy for serous and vascular pigment epithelial detachments (PED) associated with choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). Methods In a prospective study, best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) data were collected for 62 eyes of 62 patients, with serous or vascular PED associated with CNV secondary to AMD. Intravitreal ranibizumab 0.5 mg was administered with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to the retreatment criteria of the PrONTO study. The change in visual acuity and PED height from baseline to month 12 after the first injection was determined. Results Sixty-one eyes of 61 patients (one of the patients developed retinal pigment epithelial tear and was excluded from the study) were assessed at the 12-month follow-up examination. There were two types of PED, including vascular PED in 32 patients (Group A) and serous PED (Group B) in 29 patients. The mean improvement of mean BCVA from baseline to 12 months was 0.09 logMAR (Logarithm of the Minimum Angle of Resolution) in Group A and 0.13 logMAR in Group B. Both groups showed significant improvement of the mean BCVA 12 months after the first injection compared with the baseline value (P < 0.05). In relation to the PED height, the mean decrease of mean PED height from baseline to 12 months was 135 ?m in Group A and 180 ?m in Group B. Both groups showed significant reduction of the PED height during the follow-up period (P < 0.01). The PED anatomical response to ranibizumab was not correlated with the BCVA improvement in any of the groups. Apart from one patient who developed pigment epithelial tear no other complications were documented. Conclusion Ranibizumab is an effective and safe treatment for improving vision in patients with serous and vascular PED, although the anatomical response of the PED to ranibizumab may not correlate directly with the visual outcome. PMID:23874084

Panos, Georgios D; Gatzioufas, Zisis; Petropoulos, Ioannis K; Dardabounis, Doukas; Thumann, Gabriele; Hafezi, Farhad

2013-01-01

43

In vivo imaging of retinal pigment epithelium cells in age related macular degeneration  

PubMed Central

Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgan’s method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm2, which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health. PMID:24298413

Rossi, Ethan A.; Rangel-Fonseca, Piero; Parkins, Keith; Fischer, William; Latchney, Lisa R.; Folwell, Margaret A.; Williams, David R.; Dubra, Alfredo; Chung, Mina M.

2013-01-01

44

Long-Term Decrease of Retinal Pigment Epithelium Defects in Large Stage IV Macular Holes with Borders Mechanically Joined during Surgery  

PubMed Central

Purpose The aim of this paper is to present retinal pigment epithelium (RPE) defects in spectral domain optical coherence tomography (SD-OCT) and their gradual resolution over time. Materials and Methods Observational case series of 3 eyes of 3 patients who were followed for a period of 3-6 years after undergoing surgery to mechanically close the borders of large stage IV macular holes. Photoreceptor defects and RPE defects were measured during this period with SD-OCT. Results In all cases, a reduction in the size of the areas of photoreceptor and RPE defects was noted, which correlated with late improvement in visual acuity (VA). Conclusions In eyes with no underlying retinal pigment epithelial or choroidal disease, restoration of RPE is possible in vivo for up to several years after surgery for macular hole closure. An improvement in VA is possible, even lasting many years after successful macular hole surgery, which corresponds to a decrease in both RPE defects and the size of the defects in the junction between the inner and outer segments of photoreceptors. PMID:21829404

Michalewska, Zofia; Michalewski, Janusz; Nawrocki, Jerzy

2011-01-01

45

Macular telangiectasia type 2  

PubMed Central

Macular telangiectasia type 2 is a bilateral disease of unknown cause with characteristic alterations of the macular capillary network and neurosensory atrophy. Its prevalence may be underestimated and has recently been shown to be as high as 0.1% in persons 40 years and older. Biomicroscopy may show reduced retinal transparency, crystalline deposits, mildly ectatic capillaries, blunted venules, retinal pigment plaques, foveal atrophy, and neovascular complexes. Fluorescein angiography shows telangiectatic capillaries predominantly temporal to the foveola in the early phase and a diffuse hyperfluorescence in the late phase. High-resolution optical coherence tomography (OCT) may reveal disruption of the photoreceptor inner segment–outer segment border, hyporeflective cavities at the level of the inner or outer retina, and atrophy of the retina in later stages. Macular telangiectasia type 2 shows a unique depletion of the macular pigment in the central retina and recent therapeutic trials showed that such depleted areas cannot re-accumulate lutein and zeaxanthin after oral supplementation. There have been various therapeutic approaches with limited or no efficacy. Recent clinical trials with compounds that block vascular endothelial growth factor (VEGF) have established the role of VEGF in the pathophysiology of the disease, but have not shown significant efficacy, at least for the nonneovascular disease stages. Recent progress in structure–function correlation may help to develop surrogate outcome measures for future clinical trials. In this review article, we summarize the current knowledge on macular telangiectasia type 2, including the epidemiology, the genetics, the clinical findings, the staging and the differential diagnosis of the disease. Findings using retinal imaging are discussed, including fluorescein angiography, OCT, adaptive optics imaging, confocal scanning laser ophthalmoscopy, and fundus autofluorescence, as are the findings using visual function testing including visual acuity and fundus-controlled microperimetry. We provide an overview of the therapeutic approaches for both non-neovascular and neovascular disease stages and provide a perspective of future directions including animal models and potential therapeutic approaches. PMID:23219692

Issa, Peter Charbel; Gillies, Mark C.; Chew, Emily Y.; Bird, Alan C.; Heeren, Tjebo F.C.; Peto, Tunde; Holz, Frank G.; Scholl, Hendrik P.N.

2013-01-01

46

The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress.  

PubMed

Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress. PMID:25136316

Chang, Yun-Ching; Chang, Wei-Chao; Hung, Kuo-Hsuan; Yang, Der-Ming; Cheng, Yung-Hsin; Liao, Yi-Wen; Woung, Lin-Chung; Tsai, Ching-Yao; Hsu, Chih-Chien; Lin, Tai-Chi; Liu, Jorn-Hon; Chiou, Shih-Hwa; Peng, Chi-Hsien; Chen, Shih-Jen

2014-01-01

47

Autologous transplantation of genetically modified iris pigment epithelial cells: A promising concept for the treatment of age-related macular degeneration and other disorders of the eye  

NASA Astrophysics Data System (ADS)

Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.

Semkova, Irina; Kreppel, Florian; Welsandt, Gerhard; Luther, Thomas; Kozlowski, Jolanta; Janicki, Hanna; Kochanek, Stefan; Schraermeyer, Ulrich

2002-10-01

48

Aqueous levels of erythropoietin in acute retinal vein occlusion with macular edema  

PubMed Central

AIM To investigate the aqueous erythropoietin (EPO) levels and associated factors in patients with acute retinal vein occlusion (RVO). METHODS The aqueous EPO level was measured in patients with macular edema (ME) secondary to acute branched retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Aqueous fluid from cataract patients served as the control. We also evaluated whether aqueous level of EPO was associated with factors such as serum EPO level, non-perfusion area, central macular thickness (CMT), and arterio-venous (AV) transit time RESULTS Twenty-seven RVO patients (16 BRVO, 11 CRVO) and 9 control subjects were enrolled in the study. The aqueous EPO level (mU/mL) was higher in RVO (68.2±54.3) than that in the control subjects (12.9±5.9). More specifically, the aqueous EPO level was higher in CRVO (118.9±52.1) than that in BRVO (33.3±10.8). However, no differences were found in serum EPO levels among three groups. CMT in RVO patients had a positive correlation with the aqueous EPO level (r=0.66). Also, in terms of non-perfusion area, the aqueous EPO levels were more elevated in the ischemic subgroup than in the non-ischemic subgroup in both BRVO and CRVO. CONCLUSION Aqueous EPO levels are elevated in patients with macular edema secondary to recent onset RVO. Patients with CRVO have higher EPO levels than those with BRVO. The aqueous EPO level in RVO has a positive correlation with CMT and is associated with non-perfusion area. These results suggest that the aqueous EPO level could be associated with retinal ischemia and may be involved in the pathogenesis of macular edema secondary to RVO. PMID:24967199

Shin, Hyun Jin; Kim, Hyung Chan; Moon, Jun Woong

2014-01-01

49

Functional annotation of the human retinal pigment epithelium transcriptome  

Microsoft Academic Search

BACKGROUND: To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years) were laser dissected and used for 22k microarray studies (Agilent technologies). Data were analyzed with

Judith C Booij; Simone van Soest; Sigrid MA Swagemakers; Anke HW Essing; Annemieke JMH Verkerk; Peter J van der Spek; Theo GMF Gorgels; Arthur AB Bergen

2009-01-01

50

Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab  

PubMed Central

Purpose The aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab. Methods The method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab. Results Three eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes. Conclusion Intravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD. PMID:23558214

Patel, K H; Chow, C C; Rathod, R; Mieler, W F; Lim, J I; Ulanski, L J; Leiderman, Y I; Arun, V; Chau, F Y

2013-01-01

51

Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature  

PubMed Central

Background The A3243G point mutation in mitochondrial DNA (mtDNA) is associated with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and MIDD syndromes (maternally inherited diabetes and deafness). Both MELAS and MIDD patients can present with visual symptoms due to a retinopathy, sometimes before the genetic diagnosis is made. Case presentation Patient 1: 46 year-old woman with diabetes mellitus and hearing loss was referred for an unspecified maculopathy detected during screening evaluation for diabetic retinopathy. Visual acuity was 20/20 in both eyes. Fundus examination showed bilateral macular and peripapillary hyperpigmented/depigmented areas. Patient 2: 45 year-old woman was referred for recent vision loss in her left eye. History was remarkable for chronic fatigue, migraine and diffuse muscular pain. Visual acuity was 20/20 in her right eye and 20/30 in her left eye. Fundus exhibited several nummular perifoveal islands of retinal pigment epithelium atrophy and adjacent pale deposits in both eyes. Retinal anatomy was investigated with autofluorescence, retinal angiography and optical coherence tomography. Retinal function was assessed with automated static perimetry, full-field and multifocal electroretinography and electro-oculography. Genetic testing of mtDNA identified a point mutation at the locus 3243. Conclusion Observation of RPE abnormalities in the context of suggestive systemic findings should prompt mtDNA testing. PMID:24906873

2014-01-01

52

[Sodium pegaptanib and ranibizumab in the treatment of the retinal pigment layer ablation in a patient with age-related macular degeneration--a case report].  

PubMed

The case report presents the difference of the effect of two drugs blocking vascular endothelial growing factor (anti-VEGF)--sodium pegaptanib and ranibizumab--in a female patient with the retinal pigment epithelium (RPE) layer ablation as a part of the exsudative age-related macular degeneration. Fifty-five years old female patient with RPE ablation as a sign of exsudative ARMD and central visual acuity 79 letters of the EDTRS chart in the left eye was treated by 5 intravitreal injections of sodium pegaptanib. The treatment was not sufficiently effective according to the fluorescein angiography (FAG) and optic coherence tomography (OCT) findings and was accompanied by further decrease of the visual acuity to 55 letters of the EDTRS chart. After the medication was switched to ranibizumab with 3 intravitreal applications, the RPE ablation flattened according to the OCT findings and the fluorescein leakage during the FAG markedly decreased. The central visual acuity improved to 63 letters of the EDTRS chart. The decreased activity of the choroidal neovascularization (CNV) is observed during the following 4 months after the last intravitreal application of ranibizumab. Ranibizumab seems to be more effective drug comparing to the sodium pegaptanib in patients with the RPE ablation, but it is necessary to consider the increased probability of the RPE rupture risk. PMID:21137477

Sín, M; Simicák, J; Pracharová, Z; Rehák, J

2010-07-01

53

RETINAL DEIMINATION AND PAD2 LEVELS IN RETINAS FROM DONORS WITH AGE-RELATED MACULAR DEGENERATION (AMD)  

PubMed Central

Deimination is a form of protein posttranslational modification carried out by the peptidyl arginine deiminases (PADs) enzymes. PAD2 is the principal deiminase expressed in the retina. Elevated levels of PAD2 and protein deimination are present in a number of human neurological diseases, with or without ocular manifestation. To define the association of deimination with the pathogenesis of age-related macular degeneration (AMD), we studied protein deimination and PAD2 levels in retinas of AMD donor eyes compared to age-matched non-AMD retinas. Eyes from non-AMD and AMD donors were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer. Retina and retinal pigment epithelium (RPE) from donor eyes were processed for immunohistochemical detection and western blotting using antibodies to PAD2 and citrulline residues. The ganglion cell, inner plexiform, inner nuclear and outer nuclear layers were labeled by both PAD2 and citrulline antibodies. Changes in the localization of deiminated residues and PAD2 were evident as the retinal layers were remodeled coincident with photoreceptor degeneration in AMD retinas. Immunodetection of either PAD2 or citrulline residues could not be evaluated in the RPE layer due to the high autofluorescence levels in this layer. Interestingly, higher deimination immunoreactivity was detected in AMD retinal lysates. However, no significant changes in PAD2 were detected in the AMD and non-AMD retinas and RPE lysates. Our observations show increased levels of protein deimination but not PAD2 in AMD retinas and RPE, suggesting a reduced rate of turnover of deiminated proteins in these AMD retinas. PMID:23562679

Bonilha, Vera L.; Shadrach, Karen G.; Rayborn, Mary E.; Li, Yong; Pauer, Gayle J. T.; Hagstrom, Stephanie A.; Bhattacharya, Sanjoy K.; Hollyfield, Joe G.

2013-01-01

54

Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium  

Microsoft Academic Search

Best vitelliform macular dystrophy is a dominantly inherited, early onset, macular degenerative disease that exhibits some histopathologic similarities to age-related macular degeneration. Although the vitelliform lesion is common in the fundus of individuals with Best disease, diagnosis is based on a reduced ratio of the light peak to dark trough in the electrooculogram. Recently, the VMD2 gene on chromosome 11q13,

Alan D. Marmorstein; Lihua Y. Marmorstein; Mary Rayborn; Xinxing Wang; Joe G. Hollyfield; Konstantin Petrukhin

2000-01-01

55

Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration  

PubMed Central

Cigarette smoke is the most important environmental risk factor for developing age-related macular degeneration (AMD). Damage to the retinal pigment epithelium (RPE) caused by cigarette smoke may underlie the etiology of AMD. This study investigated the molecular and cellular effects of cigarette smoke exposure on human RPE cells. ARPE-19 or primary human RPE cells were exposed to cigarette smoke extract (CSE) or hydroquinone (HQ), a component of cigarette smoke. The effect of this exposure on key aspects of RPE vitality including viability, cell size, mitochondrial membrane potential (??m), superoxide production, 4-hydroxy-2-nonenal (4-HNE), vascular endothelial growth factor (VEGF), and heme oxygenase-1 (HO-1) expression was determined. Exposure of RPE cells to CSE or HQ caused oxidative damage and apoptosis, characterized by a reduction in cell size and nuclear condensation. Evidence of oxidative damage also included increased lipid peroxidation (4-HNE) and mitochondrial superoxide production, as well as a decrease in intracellular glutathione (GSH). Exogenous administration of antioxidants (GSH and N-acetyl-cysteine) prevented oxidative damage to the RPE cells caused by CSE. Cigarette smoke also induced expression of VEGF, HO-1, and the transcription factor nuclear factor erythroid-derived 2, like 2 (NRF2). However, NRF2 was only modestly involved in CSE-induced HO-1 expression, as shown by the NRF2 small interfering RNA studies. These new findings demonstrate that cigarette smoke is a potent inducer of oxidative damage and cell death in human RPE cells. These data support the hypothesis that cigarette smoke contributes to AMD pathogenesis by causing oxidative damage and cell death to RPE cells. PMID:19759330

Bertram, Kurt M.; Baglole, Carolyn J.; Phipps, Richard P.

2009-01-01

56

Subtoxic levels hydrogen peroxide-induced production of interleukin-6 by retinal pigment epithelial cells  

PubMed Central

Purpose To study the effect of subtoxic levels of hydrogen peroxide (H2O2) on the expression and release of interleukin-6 (IL-6) by cultured retinal pigment epithelial (RPE) cells and to explore the relevant signal pathways. Methods Cultured human RPE cells were stimulated with various subtoxic concentrations of H2O2 for different periods. Conditioned medium and cells were collected. IL-6 in the medium and IL-6 mRNA in the collected cells were measured using an IL-6 enzyme-linked immunosorbent assay kit and reverse transcriptase polymerase chain reaction, respectively. Nuclear factor-kappaB (NF-?B) in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases (JNK) in cells cultured with and without H2O2 were measured by NF-?B and MAPK enzyme-linked immunosorbent assay kits. Inhibitors of p38 (SB203580), ERK (UO1026), JNK (SP600125), and NF-?B (BAY11–7082) were added to the cultures before the addition of H2O2 to test their effects. Results Subtoxic levels of H2O2 (100 µM and less) increased the IL-6 mRNA level and the release of IL-6 protein by the cultured human RPE cells in a dose- and time-dependent manner. This was accompanied by an increase of NF-?B in nuclear extracts and phosphorylated p38 MAPK, ERK, and JNK in cell lysates, particularly in the p38 and NF-?B. The NF-?B inhibitor decreased the H2O2-induced expression of IL-6. The p38 inhibitor, but not the ERK or JNK inhibitor, completely abolished H2O2-induced expression of IL-6 by RPE cells. The p38 inhibitor also abolished the increase of NF-?B in nuclear extracts in cells treated with H2O2. Conclusions H2O2 stimulated the production of IL-6, a key factor in the modulation of immune responses, inflammatory processes, and the occurrence of autoimmune diseases, which recently has been documented to be increased in age-related macular degeneration (AMD). This may be a molecular linkage for the oxidative stress and inflammatory/autoimmune reactions in AMD and may provide a novel target for the treatment of AMD. PMID:21031020

Wu, Wen-Chuan; Gao, Hua-Xin; Chen, Min; Wang, Dawei; Rosen, Richard; McCormick, Steven A.

2010-01-01

57

Tumorigenicity Studies of Induced Pluripotent Stem Cell (iPSC)-Derived Retinal Pigment Epithelium (RPE) for the Treatment of Age-Related Macular Degeneration  

PubMed Central

Basic studies of human pluripotential stem cells have advanced rapidly and stem cell products are now seeing therapeutic applications. However, questions remain regarding the tumorigenic potential of such cells. Here, we report the tumorigenic potential of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of wet-type, age-related macular degeneration (AMD). First, immunodeficient mouse strains (nude, SCID, NOD-SCID and NOG) were tested for HeLa cells’ tumor-forming capacity by transplanting various cell doses subcutaneously with or without Matrigel. The 50% Tumor Producing Dose (TPD50 value) is the minimal dose of transplanted cells that generated tumors in 50% of animals. For HeLa cells, the TPD50 was the lowest when cells were embedded in Matrigel and transplanted into NOG mice (TPD50?=?101.1, n?=?75). The TPD50 for undifferentiated iPSCs transplanted subcutaneously to NOG mice in Matrigel was 102.12; (n?=?30). Based on these experiments, 1×106 iPSC-derived RPE were transplanted subcutaneously with Matrigel, and no tumor was found during 15 months of monitoring (n?=?65). Next, to model clinical application, we assessed the tumor-forming potential of HeLa cells and iPSC 201B7 cells following subretinal transplantation of nude rats. The TPD50 for iPSCs was 104.73 (n?=?20) and for HeLa cells 101.32 (n?=?37) respectively. Next, the tumorigenicity of iPSC-derived RPE was tested in the subretinal space of nude rats by transplanting 0.8–1.5×104 iPSC-derived RPE in a collagen-lined (1 mm×1 mm) sheet. No tumor was found with iPSC-derived RPE sheets during 6–12 months of monitoring (n?=?26). Considering the number of rodents used, the monitoring period, the sensitivity of detecting tumors via subcutaneous and subretinal administration routes and the incidence of tumor formation from the iPSC-derived RPE, we conclude that the tumorigenic potential of the iPSC-derived RPE was negligible. PMID:24454843

Kanemura, Hoshimi; Go, Masahiro J.; Shikamura, Masayuki; Nishishita, Naoki; Sakai, Noriko; Kamao, Hiroyuki; Mandai, Michiko; Morinaga, Chikako; Takahashi, Masayo; Kawamata, Shin

2014-01-01

58

Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration  

PubMed Central

Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1) in patients of age-related macular degeneration (AMD) and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (?2 = 10.516, df = 8, P = 0.231) indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P = .0001) with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model. PMID:24363822

Sharma, Neel K.; Gupta, Amod; Prabhakar, Sudesh; Sharma, Suresh K.; Singh, Ramandeep

2013-01-01

59

Effect of soluble inducible costimulator level and its polymorphisms on age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease. PMID:24083358

Yu, Honghua; Zou, Xiulan; Peng, Lianghong; Wang, Yong; Zhang, Chu; Chen, Bin; Zou, Yuping

2013-12-01

60

Efficacy of Ethanol Extract of Fructus lycii and Its Constituents Lutein/Zeaxanthin in Protecting Retinal Pigment Epithelium Cells against Oxidative Stress: In Vivo and In Vitro Models of Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a large role in the pathogenesis of AMD. The present study was to evaluate the effects of Fructus lycii ethanol extract on AMD in mice and to investigate whether combination of lutein and zeaxanthin, two carotenoid pigments in Fructus lycii, could protect human retinal pigment epithelial ARPE-19 cells treated with hydrogen peroxide (H2O2) in vitro. We found that severe sediment beneath retinal pigment epithelium and thickened Bruch membrane occurred in AMD mice. However, Fructus lycii ethanol extract improved the histopathologic changes and decreased the thickness of Bruch membrane. Furthermore, the gene and protein expression of cathepsin B and cystatin C was upregulated in AMD mice but was eliminated by Fructus lycii ethanol extract. Investigations in vitro showed that ARPE-19 cell proliferation was suppressed by H2O2. However, lutein/zeaxanthin not only stimulated cell proliferation but also abrogated the enhanced expression of MMP-2 and TIMP-1 in H2O2-treated ARPE-19 cells. These data collectively suggested that Fructus lycii ethanol extract and its active components lutein/zeaxanthin had protective effects on AMD in vivo and in vitro, providing novel insights into the beneficial role of Fructus lycii for AMD therapy. PMID:24163760

Xu, Xinrong; Hang, Li; Huang, Binglin; Wei, Yuanhua; Zheng, Shizhong

2013-01-01

61

Concentration levels and congener profiles of polychlorinated biphenyls, pentachlorobenzene, and hexachlorobenzene in commercial pigments.  

PubMed

The concentration levels and congener profiles of polychlorinated biphenyls (PCBs), pentachlorobenzene (PeCBz), and hexachlorobenzene (HxCBz) were assessed in commercially available organic pigments. Among the azo-type pigments tested, PCB-11, which is synthesized from 3,3'-dichlorobendizine, and PCB-52, which is synthesized from 2,2',5,5'-tetrachlorobendizine, were the major congeners detected. It is speculated that these were byproducts of chlorobendizine, which has a very similar structure. The total PCB concentrations in this type of pigment ranged from 0.0070 to 740 mg/kg. Among the phthalocyanine-type pigments, highly chlorinated PCBs, mainly composed of PCB-209, PeCBz, and HxCBz were detected. Their concentration levels ranged from 0.011 to 2.5 mg/kg, 0.0035 to 8.4 mg/kg, and 0.027 to 75 mg/kg, respectively. It is suggested that PeCBz and HxCBz were formed as byproducts and converted into PCBs at the time of synthesizing the phthalocyanine green. For the polycyclic-type pigments that were assessed, a distinctive PCB congener profile was detected that suggested an impact of their raw materials and the organic solvent used in the pigment synthesis. PCB pollution from PCB-11, PCB-52, and PCB-209 pigments is of particular concern; therefore, the monthly variations in atmospheric concentrations of these pollutants were measured in an urban area (Sapporo city) and an industrial area (Muroran city). The study detected a certain level of PCB-11, which is not included in PCB technical mixtures, and revealed continuing PCB pollution originating from pigments in the ambient air. PMID:23852585

Anezaki, Katsunori; Nakano, Takeshi

2014-01-01

62

Candidate gene study of macular response to supplemental lutein and zeaxanthin?  

PubMed Central

Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism. PMID:23891863

Yonova-Doing, Ekaterina; Hysi, Pirro G.; Venturini, Cristina; Williams, Katie M.; Nag, Abhishek; Beatty, Stephen; Liew, S.H. Melissa; Gilbert, Clare E.; Hammond, Christopher J.

2013-01-01

63

Candidate gene study of macular response to supplemental lutein and zeaxanthin.  

PubMed

Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism. PMID:23891863

Yonova-Doing, Ekaterina; Hysi, Pirro G; Venturini, Cristina; Williams, Katie M; Nag, Abhishek; Beatty, Stephen; Liew, S H Melissa; Gilbert, Clare E; Hammond, Christopher J

2013-10-01

64

Genetics and molecular pathology of Stargardt-like macular degeneration  

Microsoft Academic Search

Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third

Vidyullatha Vasireddy; Paul Wong; Radha Ayyagari

2010-01-01

65

Genetic basis of continuous variation in the levels and modular inheritance of pigmentation in cichlid fishes.  

PubMed

Variation in pigmentation type and levels is a hallmark of myriad evolutionary radiations, and biologists have long been fascinated by the factors that promote and maintain variation in coloration across populations. Here, we provide insights into the genetic basis of complex and continuous patterns of colour variation in cichlid fishes, which offer a vast diversity of pigmentation patterns that have evolved in response to both natural and sexual selection. Specifically, we crossed two divergent cichlid species to generate an F2 mapping population that exhibited extensive variation in pigmentation levels and patterns. Our experimental design is robust in that it combines traditional quantitative trait locus (QTL) analysis with population genomics, which has allowed us to move efficiently from QTL interval to candidate gene. In total, we detected 41 QTL and 13 epistatic interactions that underlie melanocyte- and xanthophore-based coloration across the fins and flanks of these fishes. We also identified 2 QTL and 1 interaction for variation in the magnitude of integration among these colour traits. This finding in particular is notable as there are marked differences both within and between species with respect to the complexity of pigmentation patterns. While certain individuals are characterized by more uniform 'integrated' colour patterns, others exhibit many more degrees of freedom with respect to the distribution of colour 'modules' across the fins and flank. Our data reveal, for the first time, a genetic basis for this difference. Finally, we implicate pax3a as a mediator of continuous variation in the levels of xanthophore-based colour along the cichlid flank. PMID:25156298

Albertson, R Craig; Powder, Kara E; Hu, Yinan; Coyle, Kaitlin P; Roberts, Reade B; Parsons, Kevin J

2014-11-01

66

Genetic basis of continuous variation in the levels and modular inheritance of pigmentation in cichlid fishes  

PubMed Central

Variation in pigmentation type and levels is a hallmark of myriad evolutionary radiations, and biologists have long been fascinated by the factors that promote and maintain variation in coloration across populations. Here, we provide insights into the genetic basis of complex and continuous patterns of colour variation in cichlid fishes, which offer a vast diversity of pigmentation patterns that have evolved in response to both natural and sexual selection. Specifically, we crossed two divergent cichlid species to generate an F2 mapping population that exhibited extensive variation in pigmentation levels and patterns. Our experimental design is robust in that it combines traditional quantitative trait locus (QTL) analysis with population genomics, which has allowed us to move efficiently from QTL interval to candidate gene. In total, we detected 41 QTL and 13 epistatic interactions that underlie melanocyte- and xanthophore-based coloration across the fins and flanks of these fishes. We also identified 2 QTL and 1 interaction for variation in the magnitude of integration among these colour traits. This finding in particular is notable as there are marked differences both within and between species with respect to the complexity of pigmentation patterns. While certain individuals are characterized by more uniform ‘integrated’ colour patterns, others exhibit many more degrees of freedom with respect to the distribution of colour ‘modules’ across the fins and flank. Our data reveal, for the first time, a genetic basis for this difference. Finally, we implicate pax3a as a mediator of continuous variation in the levels of xanthophore-based colour along the cichlid flank. PMID:25156298

Albertson, R. Craig; Powder, Kara E.; Hu, Yinan; Coyle, Kaitlin P.; Roberts, Reade B.; Parsons, Kevin J.

2014-01-01

67

Genetic and molecular studies of macular dystrophies: recent developments  

Microsoft Academic Search

Macular degeneration is a heterogeneous group of disorders characterized by progressive central visual loss and degeneration of the macula and underlying retinal pigment epithelium (RPE) of the eye. Age-related macular degeneration (ARMD), the most common form of the disease, is the leading cause of legal blindness in the elderly population in the United States and in the many developed countries

Kang Zhang; Alan Crandall; Larry A. Donoso

1995-01-01

68

Pegaptanib sodium as maintenance therapy in neovascular age-related macular degeneration: the LEVEL study  

PubMed Central

Aim To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. Methods A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30–120?days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275??m or less or thinning of 100??m or more (optical coherence tomography); visual acuity (VA) 20/20–20/400. Intravitreal pegaptanib 0.3?mg was administered as maintenance every 6?weeks for 48?weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Results Of 568 enrolled subjects, 86% completed 1?year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20??m increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147?days after maintenance initiation). Conclusions An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD. PMID:20472746

Tolentino, Michael

2010-01-01

69

Correlation of Vitamin D Levels with Pigmentation in Vitiligo Patients Treated with NBUVB Therapy.  

PubMed

Cholecalciferol (vitamin D) might play a physiological role in photo-induced melanogenesis in human skin. We estimated the levels of 25-hydroxy vitamin D [25(OH)D] before, during, and after Narrow Band Ultraviolet B (NBUVB) radiation in patients of vitiligo and their correlation with NBUVB induced pigmentation. Thirty patients of vitiligo and equal number of age and sex matched controls were recruited for the study. Vitiligo patients were treated with NBUVB thrice weekly for 12 weeks. [25(OH)D] levels and Vitiligo Area and Severity Index (VASI) were calculated at 0 (baseline), 6, and 12 weeks. Baseline [25(OH)D] levels were measured in controls. Significant reduction in VASI score was observed after 12 weeks of therapy. Comparison and correlation between mean improvement in VASI and [25(OH)D] levels at 12 weeks showed moderate correlation, and the results were statistically insignificant. Mean reduction in VASI and increase in [25(OH)D] levels after 12 weeks of NBUVB showed moderate correlation. Thus, vitamin D might play a significant role in photo-induced melanogenesis. However, there might be additional effects of the phototherapy on melanogenesis. The complete mechanism of NBUVB induced pigmentation in vitiligo needs to be elucidated. PMID:25006488

Sehrawat, Manu; Arora, Tarlok Chand; Chauhan, Amrita; Kar, Hemanta Kumar; Poonia, Amitabh; Jairath, Vijayeeta

2014-01-01

70

[The potential role of oxidative stress in the pathogenesis of the age-related macular degeneration (AMD)].  

PubMed

Age-related macular degeneration (AMD) is one of the most important causes of blindness among the elderly. Although the disease presents a serious social problem, its pathogenesis is still unclear. AMD involves the posterior pole of the retina, the place responsible for acute vision. Retinal factors (intensive oxygen metabolism, continual exposure to light, a high concentration of polyunsaturated fatty acids, the presence of photosensitizers) increase the production of reactive oxygen species. Oxidative stress is aggravated by the presence of lipofuscin. The pigment accumulates with age, especially in the eyes of those with AMD. The most important risk factors for AMD, beside genetic predisposition, are factors leading to oxidative stress in the retina, e.g. age above 65 years, cigarettes smoking, obesity, exposition to blue light, and bright irises. Macular pigment is a natural barrier protecting the central retina against oxidative damage. It is formed by two dihydroxycarotenoids, lutein and zeaxanthin. The prereceptoral location of the macular pigment permits it to act as an optical filter that absorbs short-wavelength visible light. Carotenoids also demonstrate antioxidant activity. Eyes with a predisposition to develop AMD or which already have developed the disease have considerably less macular pigment and a greater risk of oxidative damage compared with healthy eyes. Investigations have shown that diet poor in antioxidant micronutrients (vitamin C, E, carotenoids, zinc) and low plasma levels of antioxidants may favor the development of the age-related macular degeneration. The findings demonstrated that micronutrient supplementation enhances antioxidant defense and might prevent or retard AMD or modify the course of the disease. PMID:17245315

Drobek-S?owik, Monika; Karczewicz, Danuta; Safranow, Krzysztof

2007-01-01

71

Relation Between the Incidence and Level of Pigment Cell Antibodies and Disease Activity in Vitiligo  

Microsoft Academic Search

Patients with vitiligo often have antibodies to pigment cells. To examine whether is relation between the presence of such antibodies and disease activity, sera of 24 patients with vitiligo (10 with active and 14 with inactive disease) and 19 normal individual were tested for antibodies to pigment cell surface antigens using a live cell enzyme-linked immunoabsorbent assay. IgG pigment cell

Ronald Harning; Jian Cui; Jean-Claude Bystryn

1991-01-01

72

Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex.  

PubMed

There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch's membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85-90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10-15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex. PMID:22542780

Bhutto, Imran; Lutty, Gerard

2012-08-01

73

Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex  

PubMed Central

There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch’s membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85–90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10–15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex. PMID:22542780

Bhutto, Imran; Lutty, Gerard

2012-01-01

74

Serum level of pigment epithelium derived factor (PEDF) is an independent determinant of resting heart rate in Japanese subjects  

Microsoft Academic Search

We have recently found that serum level of pigment epithelium derived factor (PEDF) is significantly increased in proportion to the accumulation of the number of the components of the metabolic syndrome. Although high heart rate is also associated with metabolic risk factors for atherosclerosis, the correlation between serum level of PEDF and resting heart rate remains to be elucidated. In

Kazuo Nakamura; Sho-ichi Yamagishi; Hisashi Adachi; Takanori Matsui; Yayoi Kurita; Hiroyoshi Inoue

2009-01-01

75

Adhesive protein-free synthetic hydrogels for retinal pigment epithelium cell culture with low ROS level.  

PubMed

Engineering of human retinal pigment epithelium (RPE) cell monolayer with low level of reactive oxygen species (ROS) is important for regenerative RPE-based therapies. However, it is still challenging to culture RPE monolayer with low ROS level on soft substrates in vitro. To address this, we developed cytocompatible hydrogels to culture human RPE cell monolayer for future use in regenerative RPE-based therapies. The cell adhesion, proliferation, monolayer formation, morphology, survival, and ROS level of human ARPE-19 cells cultured on the surfaces of negatively charged poly (2-acrylamido-2-methyl propane sulfonic sodium) (PNaAMPS) and neutral poly(N,N-dimethylacrylamide) (PDMAAm) hydrogels with different stiffness were investigated. The importance of hydrogel stiffness on the cell function was firstly highlighted on the base of determined optimal Young's modulus for cultivation of RPE cell monolayer with relatively low ROS level. The construction of RPE cell monolayer with low ROS level on the PNaAMPS hydrogel may hold great potential as promising candidates for transplantation of RPE cell monolayer-hydrogel construct into the subretinal space to repair retinal functions. PMID:23913900

Chen, Yong Mei; Liu, Zhen Qi; Feng, Zhi Hui; Xu, Feng; Liu, Jian Kang

2014-07-01

76

Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration  

Microsoft Academic Search

· Background: Macular rotation to treat exudative age-related macular degeneration (AMD) involves translocation of the fovea\\u000a to a site with intact retinal pigment epithelium. To avoid the inevitable postoperative cyclotropia we combined this procedure\\u000a with torsional muscle surgery.?· Patients and methods: In 30 eyes the macula was rotated upward by 30–50° following complete\\u000a artificial retinal detachment and a 360° retinotomy.

Claus Eckardt; Ute Eckardt; Hans-Georg Conrad

1999-01-01

77

Skin pigmentation, sun exposure and vitamin D levels in children of the Avon Longitudinal Study of Parents and Children  

PubMed Central

Background It has been hypothesised that light skin pigmentation has arisen to ensure adequate levels of vitamin D as human populations moved out of Africa and into higher latitudes. Vitamin D, which is primarily obtained through exposure to sunlight (specifically ultraviolet radiation B (UVR-B)), has been inversely associated with several complex diseases. Greater sun exposure, on the other hand, is a well-known cause of skin cancer. The potential of UVR to be beneficial for some health outcomes but detrimental for others has prompted a public health debate on how to balance the positive and negative consequences of sun exposure. In this study we aimed to determine the validity of the evolutionary hypothesis linking lighter skin with higher vitamin D concentrations in a European population. Additionally, we aimed to examine the influence of pigmentation on personal behaviour towards sunlight exposure and the effects of this behaviour on vitamin D. Methods We combined genetic variants strongly associated with skin colour, tanning or freckling to create genetic scores for each of these phenotypes. We examined the association of the scores with pigmentary traits, sun exposure and serum 25-hydroxyvitamin D (25(OH)D) levels among children of the Avon Longitudinal Study of Parents and Children (ALSPAC, N?=?661 to 5649). Results We found that fairer-skinned children, i.e. those with higher pigmentation score values, had higher levels of 25(OH)D (0.6 nmol/l; 95% CI 0.2, 1.0; per unit increase in skin colour score; N?=?5649). These children also used more protection against the damaging effects of UVR. Conclusions In this population taking protective measures against sunburn and skin cancer does not seem to remove the positive effect that having a less pigmented skin has on vitamin D production. Our findings require further replication as skin pigmentation showed only a small effect on circulating 25(OH)D. PMID:24924479

2014-01-01

78

Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration  

Microsoft Academic Search

Background: Retinal pigment epithelial (RPE) cells have been transplanted to replace the RPE cells lost after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration. The purpose of this study was to analyze the visual function of eyes with altered RPE after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration, and to determine

Toshiaki Abe; Madoka Yoshida; Tetsuya Kano; Makoto Tamai

2001-01-01

79

The monochromatic green argon laser in the management of macular disorders.  

PubMed

The authors have been using an argon laser photocoagulator equipped with a green filter for about 21/2 years. Compared to the usual blue-green argon laser, the advantage of such an instrument is that green radiation is not absorbed to any significant degree by macular pigment. This ensures a selective action on hemoglobin and pigment epithelium. The green wavelength appears to be extremely useful in the management of macular disorders. The authors report the criteria they follow and the technique they use in the treatment of subretinal neovascular membranes and of macular edema arising from different retinal vascular disorders. PMID:4039398

Gazocchi, M; Fattori, C M; Gratton, I; Simonini, F; Citroni, M

1985-01-01

80

Accelerated Accumulation of Lipofuscin Pigments in the RPE of a Mouse Model for ABCA4-Mediated Retinal Dystrophies following Vitamin A Supplementation  

PubMed Central

Purpose Dietary supplementation with vitamin A is sometimes prescribed as a treatment for retinitis pigmentosa, a group of inherited retinal degenerations that cause progressive blindness. Loss-of-function mutations in the ABCA4 gene are responsible for a subset of recessive retinitis pigmentosa. Other mutant alleles of ABCA4 cause the related diseases, recessive cone-rod dystrophy, and recessive Stargardt macular degeneration. Mice with a knockout mutation in the abca4 gene massively accumulate toxic lipofuscin pigments in the retinal pigment epithelium. Treatment of these mice with fenretinide, an inhibitor of vitamin A delivery to the eye, blocks formation of these toxic pigments. Here the authors tested the hypothesis that dietary supplementation with vitamin A may accelerate lipofuscin pigment formation in abca4?/? mice. Methods Wild-type and abca4?/? mice were fed normal or vitamin A–supplemented diets. Tissues from these mice were analyzed biochemically for retinoids and lipofuscin pigments. Eyes from these mice were analyzed morphologically for lipofuscin in the retinal pigment epithelium and for degeneration of photoreceptors. Visual function in these mice was analyzed by electroretinography. Results Mice that received vitamin A supplementation had dramatically higher levels of retinyl esters in the liver and retinal pigment epithelium. Lipofuscin pigments were significantly increased by biochemical and morphologic analysis in wild-type and abca4?/? mice fed the vitamin A–supplemented diet. Photoreceptor degeneration was observed in 11-month-old albino, but not pigmented, abca4?/? mice on both diets. Conclusions Vitamin A supplementation should be avoided in patients with ABCA4 mutations or other retinal or macular dystrophies associated with lipofuscin accumulation in the retinal pigment epithelium. PMID:18515570

Radu, Roxana A.; Yuan, Quan; Hu, Jane; Peng, Jennifer H.; Lloyd, Marcia; Nusinowitz, Steven; Bok, Dean; Travis, Gabriel H.

2010-01-01

81

In vitro Transplantation of Fetal Human Retinal Pigment Epithelial Cells onto Human Cadaver Bruch's Membrane  

Microsoft Academic Search

Retinal pigment epithelium transplantation has been proposed as adjunctive treatment for age-related macular degeneration following surgical excision of choroidal neovascular membranes. The goal of this study was to develop a model to evaluate retinal pigment epithelium transplantation onto human Bruch's membrane in vitro. We investigated the ability of cultured fetal human retinal pigment epithelium to colonize human cadaver Bruch's membrane,

ALESSANDRO A. CASTELLARIN; ILENE K. SUGINO; JOSEPH A. VARGAS; BARBARA PAROLINI; GE MING LUI; MARCO A. ZARBIN

1998-01-01

82

Keypathophysiologic pathways in age-related macular disease  

Microsoft Academic Search

Purpose To review current knowledge of key pathogenetic pathways in age-related macular disease (AMD). Methods Experimental evidence and clinical observations are reviewed. Results A number of common downstream pathophysiologic pathways appear to be relevant in AMD manifestations irrespective of primary heterogeneous etiologies. These include sequelae of oxidative damage, retinal pigment epithelium (RPE) cell dysfunction with accumulation of lipofuscin and impairment

Felix Roth; Almut Bindewald; Frank G. Holz

2004-01-01

83

Genetic and molecular studies of macular dystrophies: recent developments.  

PubMed

Macular degeneration is a heterogeneous group of disorders characterized by progressive central visual loss and degeneration of the macula and underlying retinal pigment epithelium (RPE) of the eye. Age-related macular degeneration (ARMD), the most common form of the disease, is the leading cause of legal blindness in the elderly population in the United States and in the many developed countries throughout the world. Despite its prevalence, its etiology and pathogenesis are poorly understood, and effective treatment options are limited for most patients. Inherited macular dystrophies share many important features with ARMD but are more readily studied by molecular genetic approaches. Over the past few years, significant progress has been made in the molecular genetics of inherited macular dystrophies. Genes responsible for dominant and recessive Stargardt's macular dystrophy as well as Best's disease have been localized to specific chromosomal regions. The peripherin/RDS gene when defective is associated with butterfly-shaped pattern dystrophy. Molecular studies of genes involved in macular dystrophies may yield insights into the mechanisms of pathogenesis of macular degeneration and provide new rationale for the management and treatment of patients with these diseases. PMID:8545803

Zhang, K; Nguyen, T H; Crandall, A; Donoso, L A

1995-01-01

84

Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration  

Microsoft Academic Search

Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a

G. Karan; C. Lillo; Z. Yang; D. J. Cameron; K. G. Locke; Y. Zhao; S. Thirumalaichary; C. Li; D. G. Birch; H. R. Vollmer-Snarr; D. S. Williams; K. Zhang

2005-01-01

85

Impact of the Common Genetic Associations of Age-Related Macular Degeneration upon Systemic Complement Component C3d Levels  

PubMed Central

Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p?=?0.002), higher age (p?=?1.56×10?7), AMD phenotype (p?=?1.15×10?11) and the two SNPs in the C3 gene rs6795735 (p?=?0.04) and rs2230199 (p?=?0.04). Lower C3d/C3 ratios were found for diabetes (p?=?2.87×10?6), higher body mass index (p?=?1.00×10?13), the SNPs rs1410996 (p?=?0.0001), rs800292 (p?=?0.003), rs12144939 (p?=?4.60×10?6) in CFH, rs4151667 (p?=?1.01×10?5) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation. PMID:24675670

Ristau, Tina; Paun, Constantin; Ersoy, Lebriz; Hahn, Moritz; Lechanteur, Yara; Hoyng, Carel; de Jong, Eiko K.; Daha, Mohamed R.; Kirchhof, Bernd; den Hollander, Anneke I.; Fauser, Sascha

2014-01-01

86

American Macular Degeneration Foundation  

MedlinePLUS

... A + A Search Search Welcome Welcome to the American Macular Degeneration Foundation web site where you can ... the United States, affecting more than ten million Americans. This time-lapse animation illustrates the central vision ...

87

Cystoid macular edema  

PubMed Central

We review the epidemiology, pathophysiology, and etiology of cystoid macular edema (CME). Inflammatory, diabetic, post-cataract, and macular edema due to age-related macular degeneration is described. The role of chronic inflammation and hypoxia and direct macular traction is evaluated in each case according to different views from the literature. The different diagnostic methods for evaluating the edema are described. Special attention is given to fluoroangiography and the most modern methods of macula examination, such as ocular coherence tomography and multifocal electroretinography. Finally, we discuss the treatment of cystoid macular edema in relation to its etiology. In this chapter we briefly refer to the therapeutic value of laser treatment especially in diabetic maculopathy or vitrectomy in some selected cases. Our paper is focused mainly on recent therapeutic treatment with intravitreal injection of triamcinolone acetonide and anti-VEGF factors like bevacizumab (Avastin), ranibizumab (Lucentis), pegaptamid (Macugen), and others. The goal of this paper is to review the current status of this treatment for macular edema due to diabetic maculopathy, central retinal vein occlusion and post-cataract surgery. For this reason the results of recent multicenter clinical trials are quoted, as also our experience on the use of intravitreal injections of anti-VEGF factors and we discuss its value in clinical practice. PMID:19668445

Rotsos, Tryfon G; Moschos, Marilita M

2008-01-01

88

Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients  

Microsoft Academic Search

Background: Heterozygous mutations of the bestrophin gene are associated with Best macular dystrophy (BMD). The bestrophin gene is specifically\\u000a expressed in the retinal pigment epithelium. BMD is a hereditary form of macular degeneration that may develop subretinal\\u000a neovascularisation similar to the wet type of age-related macular degeneration (AMD). Purpose: To study whether mutations of the bestrophin gene occur in non-familial

Akiko Akimoto; Masayuki Akimoto; Sachiko Kuroiwa; Takanobu Kikuchi; Nagahisa Yoshimura

2001-01-01

89

Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization  

Microsoft Academic Search

PURPOSE: To report a case of retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization.METHODS: Case report. A 74-year-old woman with exudative age-related macular degeneration and classic subfoveal choroidal neovascularization RE underwent photodynamic therapy with verteporfin.RESULTS: Ophthalmoscopy and fluorescein angiography RE disclosed a retinal pigment epithelial tear in the area of photodynamic therapy.CONCLUSION: This case presents the first report

Faik Gelisken; Werner Inhoffen; Michael Partsch; Ulrike Schneider; Ingrid Kreissig

2001-01-01

90

Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration  

Microsoft Academic Search

Recently, the VMD2 gene has been identified as the causative gene in juvenile-onset vitelliform macular dystrophy (Best disease), a central retinopathy primarily characterised by an impaired function of the retinal pigment epithelium. In this study we have further characterised the spectrum of VMD2 mutations in a series of 41 unrelated Best disease patients. Furthermore we expanded our analysis to include

Franziska Krämer; Karen White; Daniel Pauleikhoff; Andrea Gehrig; Lori Passmore; Andrea Rivera; Günther Rudolph; Ulrich Kellner; Monika Andrassi; Birgit Lorenz; Klaus Rohrschneider; Anita Blankenagel; Bernhard Jurklies; Harald Schilling; Florian Schütt; Frank G Holz; Bernhard HF Weber

2000-01-01

91

FOOD LEVEL IN RELATION TO RATE OF DEVELOPMENT AND EYE PIGMENTATION IN DROSOPHILA MELANOGASTER  

Microsoft Academic Search

Beadle and Law (1938) have shown that the eye color hormones concerned in the differentiation of vermilion and cinmibar eye colors in Drosophila melanogaster are effective when administered with larval food. In attempting to develop a standardized method of feeding these hormones quantitatively, it became evident that information was needed on the relation between food-level and rate of development (see

G. W. BEADLE; EDWARD L TATUM; C. W. CLANCY

92

Fundus Imaging of Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Digital fundus cameras and confocal scanning laser ophthalmoscopes have increased the efficiency and resolution of fundus\\u000a photography. Autofluorescent images yield information about the functional status of the outer retina and retinal pigment\\u000a epithelium (RPE). Fluorescein angiography remains invaluable for studying retinal vascular anatomy and physiology in eyes\\u000a with neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) permits visualization of

Allen Chiang; Andre J. Witkin; Carl D. Regillo; Allen C. Ho

93

Immunopathological aspects of age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological\\u000a aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic\\u000a processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and\\u000a beneath the retinal pigment epithelium, recruitment of macrophages for

Mrinali Patel; Chi-Chao Chan

2008-01-01

94

Levels of Aqueous Humor Trace Elements in Patients with Non-Exsudative Age-related Macular Degeneration: A Case-control Study  

PubMed Central

Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD. For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards. Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 µmol/L, IQR: 0.40–0.84 vs. 0.06 µmol/L; IQR: 0.01–.018; p?=?0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62–3.15 vs. 1.17 µmol/L; IQR: 0.95–1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289–329 vs. 129 µmol/L; IQR: 111–145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9–32.6 vs. 5.1 µmol/L; IQR: 4.4–9.4; p?=?0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4–31.3 vs. 49.9 µmol/L; IQR: 32.0–.142.0; p?=?0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD. Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD. PMID:23457607

Jünemann, Anselm G. M.; Stopa, Piotr; Michalke, Bernhard; Chaudhri, Anwar; Reulbach, Udo; Huchzermeyer, Cord; Schlötzer-Schrehardt, Ursula; Kruse, Friedrich E.; Zrenner, Eberhart; Rejdak, Robert

2013-01-01

95

The Psychosocial Impact of Macular Degeneration  

Microsoft Academic Search

Background: Age-related macular degeneration (AMD), the leading cause of irreversible blindness and low vi- sion among the elderly, has not been well studied with regard to its impact on daily life. This study was de- signed to demonstrate the impact of AMD on quality of life, emotional distress, and functional level. Participants: The study sample consisted of 86 elderly adults

Rebecca A. Williams; Barbara L. Brody; Ronald G. Thomas; Robert M. Kaplan; Stuart I. Brown

1998-01-01

96

VEGF Modulation of Retinal Pigment Epithelium Resistance  

PubMed Central

Fluid accumulation into the subretinal space and the development of macular edema is a common condition in age-related macular degeneration, diabetic retinopathy, and following ocular surgery, or injury. Vascular endothelial growth factor (VEGF) and other cytokines have been implicated in the disruption of retinal pigment epithelium (RPE) barrier function and a reduction in the regulated removal of subretinal fluid; however, the cellular and molecular events linking these agents to the disruption of barrier function have not been established. In the current study, cultures of ARPE-19 and primary porcine retinal pigment epithelium (RPE) cells were utilized to investigate the effects of the VEGF-induced modifications to the barrier properties of the RPE. The barrier function was determined by transepithelial resistance (TER) measurements and morphology of the RPE monolayers. In both ARPE-19 and primary porcine RPE cells the administration of VEGF produced a significant drop in TER, and this response was only observed following apical administration. Maximum reduction in TER was reached 5 hours post VEGF administration. These responses were concentration-dependent with an EC50 of 502 pg/mL in ARPE-19 cells and 251 pg/mL in primary porcine cells. In both ARPE-19 and primary RPE cells, the response to VEGF was blocked by pretreatment with the relatively selective VEGF-R2 antagonists, SU5416 or ZM323881, or the protein tyrosine kinase inhibitor, genistein. Administration of the relatively selective VEGF-R2 agonist, VEGF-E, also reduced TER in a concentration-dependent manner (EC50 of 474 pg/mL), while VEGF-R1 agonist, placental growth factor (PlGF), did not significantly alter the TER. Immunolocalization studies demonstrated that confluent monolayers exhibited continuous cell-to-cell ZO-1 protein contacts and apical localization of the VEGF-R2 receptors. These data provide evidence that the VEGF-induced breakdown of RPE barrier function is mediated by the activation of apically-oriented VEGF-R2 receptors. Thus, VEGF-mediated increases in RPE permeability are initiated by a rise in intraocular levels of VEGF. PMID:17915218

Ablonczy, Zsolt; Crosson, Craig E.

2008-01-01

97

Eye Pigment May Help Vision in Hazy Conditions  

MedlinePLUS

... page, please enable JavaScript. Eye Pigment May Help Vision in Hazy Conditions Yellow pigment boosts the ability ... hazy conditions in order to test the distance vision of people with different levels of yellow pigment ( ...

98

Low-level night-time light therapy for age-related macular degeneration (ALight): study protocol for a randomized controlled trial  

PubMed Central

Background Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. The only treatments currently available, such as ranibizumab injections, are for neovascular AMD, which accounts for only 10 to 15% of people with the condition. Hypoxia has been implicated as one of the primary causes of AMD, and is most acute at night when the retina is most metabolically active. By increasing light levels at night, the metabolic requirements of the retina and hence the hypoxia will be considerably reduced. This trial seeks to determine whether wearing a light mask that emits a dim, green light during the night can prevent the progression of early AMD. Methods/design ALight is a Phase I/IIa, multicentre, randomized controlled trial. Sixty participants (55 to 88 years old) with early AMD in one eye and neovascular AMD (nAMD) in the fellow eye will be recruited from nAMD clinics. They will be randomized (in the ratio 1:1), either to receive the intervention or to be in the untreated control group, stratified according to risk of disease progression. An additional 40 participants with healthy retinal appearance, or early AMD only, will be recruited for a baseline cross-sectional analysis. The intervention is an eye mask that emits a dim green light to illuminate the retina through closed eyelids at night. This is designed to reduce the metabolic activity of the retina, thereby reducing the potential risk of hypoxia. Participants will wear the mask every night for 12 months. Ophthalmologists carrying out monthly assessments will be masked to the treatment group, but participants will be aware of their treatment group. The primary outcome measure is the proportion of people who show disease progression during the trial period in the eye with early AMD. A co-primary outcome measure is the rate of retinal adaptation. As this is a trial of a CE-marked device for an off-label indication, a further main aim of this trial is to assess safety of the mask in the cohort of participants with AMD. Trial registration International Standard Randomised Controlled Trials Register: ISRCTN82148651 PMID:24965385

2014-01-01

99

Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies  

Microsoft Academic Search

Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration\\u000a characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated\\u000a with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for\\u000a the disease, and identified a number of causative mutations

Rando Allikmets; Johanna M. Seddon; Paul S. Bernstein; Amy Hutchinson; Andrew Atkinson; Sanjay Sharma; Bernard Gerrard; Wen Li; Michael L. Metzker; Claes Wadelius; C. Thomas Caskey; Michael Dean; Konstantin Petrukhin

1999-01-01

100

Autoantibodies to retinal astrocytes associated with age-related macular degeneration  

Microsoft Academic Search

Sera from 128 patients with age-related macular degeneration (AMD) were examined and profiles of a variety of serum constituents, including immunoglobulins, alpha and beta globulins and autoantibodies, were tabulated. A similar series of tests were carried out on 20 control sera. The results indicate a higher incidence of serum abnormalities, particularly involving alpha-2 globulin, in patients with disturbance of pigmentation

Philip L. Penfoldi; Jan M. Provis; Judith H. Furby; Paul A. Gatenby; Francis A. Billson

1990-01-01

101

In vivo micropathology of Best macular dystrophy with optical coherence tomography  

Microsoft Academic Search

Best macular dystrophy (BMD) is an autosomal dominant retinopathy caused by mutations in the VMD2 gene that encodes a chloride channel in the basolateral membrane of the retinal pigment epithelium (RPE). BMD patients were studied using optical coherence tomography (OCT) to understand the disease process in the macula leading to vision loss. BMD patients (ages 5–61), representing four families with

Michael J. Pianta; Tomas S. Aleman; Artur V. Cideciyan; Janet S. Sunness; Yuanyuan Li; Betsy A. Campochiaro; Peter A. Campochiaro; Donald J. Zack; Edwin M. Stone; Samuel G. Jacobson

2003-01-01

102

Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging  

PubMed Central

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

Ardeljan, Daniel; Chan, Chi-Chao

2013-01-01

103

Multiple extra macular branch retinal vein occlusions in hyperhomocysteinemia  

PubMed Central

Hyperhomocysteinemia is a well-known modifiable risk factor for thromboembolism. Retinal vascular occlusion in patients having hyperhomocysteinemia is a known entity, particularly in young patients. However, multiple extra macular branch retinal vein occlusion (BRVO) is a rare condition, which can be a presentation of this disease. We present a patient who had multiple extra macular BRVO; on complete systemic workup, he was found to have raised homocysteine levels. PMID:24817751

Gore, Abhijit Diwakar; Rao, Girish Shiva; Gore, Mansi Abhijit; Desai, Abhishek R

2014-01-01

104

Vitreoretinal surgery for macular hole after laser assisted in situ keratomileusis for the correction of myopia  

PubMed Central

Ams: To describe the characteristics and surgical outcomes of full thickness macular hole surgery after laser assisted in situ keratomileusis (LASIK) for the correction of myopia. Methods: 13 patients (14 eyes) who developed a macular hole after bilateral LASIK for the correction of myopia participated in the study. Results: Macular hole formed 1–83 months after LASIK (mean 13 months). 11 out of 13 (84.6%) patients were female. Mean age was 45.5 years old (25–65). All eyes were myopic (range ?0.50 to ?19.75 dioptres (D); mean ?8.4 D). Posterior vitreous detachment (PVD) was not present before and was documented after LASIK on 42.8% of eyes. Most macular hole were unilateral, stage 4 macular hole, had no yellow deposits on the retinal pigment epithelium, had no associated epiretinal membrane, were centric, and had subretinal fluid. The mean diameter of the hole was 385.3 ?m (range 200–750 ?m). A vitrectomy closed the macular hole on all eyes with an improvement on final best corrected visual acuity (VA) on 13 out of 14 (92.8%) patients. Conclusions: This study shows that vitreoretinal surgery can be successful in restoring vision for most myopic eyes with a macular hole after LASIK. PMID:16234445

Arevalo, J F; Rodriguez, F J; Rosales-Meneses, J L; Dessouki, A; Chan, C K; Mittra, R A; Ruiz-Moreno, J M

2005-01-01

105

Molecular genetics of macular degeneration  

Microsoft Academic Search

Macular degeneration is a leading cause of blindness that affects the aged population. The complexity of the molecular basis of macular disease is now beginning to be elucidated with the identification of disease-causing genes. For example, mutations in the ABCR gene, (recently identified in cones as well) which codes for retinal rod-specific ABCR protein is responsible for Stargardt macular dystrophy\\/fundus

Maria A. Musarella

2001-01-01

106

Macular hole in juvenile X-linked retinoschisis  

PubMed Central

An 18 year-old male with no antecedent of trauma, systemic syndrome or myopia was referred for surgical treatment of a full thickness macular hole in the left eye. A more careful inspection revealed discrete foveal cystic changes in the fellow eye and subtle peripheral depigmented retinal pigment epithelial changes in both eyes. A spectral-domain optical coherence tomography (SD-OCT) scan confirmed, in addition to the full thickness macular hole in the left eye, microcystic spaces in the nuclear layers of both retinae. The diagnosis of X-linked retinoschisis was confirmed with a full field electroretinogram displaying the typical negative ERG. Macular holes are uncommon in the young and those complicating X-linked retinoschisis are rare. This report highlights the importance of investigating the presence of a macular hole in a young patient and illustrates the clinical and SD-OCT clues beyond the foveal center which led to the correct diagnosis of X-linked juvenile retinoschisis. PMID:24409088

Al-Swaina, Nayef; Nowilaty, Sawsan R.

2013-01-01

107

Induction of anthocyanin pigments in callus cultures of Rosa hybrida L. in response to sucrose and ammonical nitrogen levels  

Microsoft Academic Search

The influence of varied concentrations of sucrose and ammonical (NH4+) nitrogen on in vitro induction and expression of anthocyanin pigments from Rosa hybrida cv. ‘Pusa Ajay’ was investigated. Of two explants (petal and leaf discs) selected and cultured under two different conditions\\u000a (light and dark), leaf discs were found to be most suitable for callus initiation. Profuse and early callus induction

Mohan Ram; K. V. Prasad; Charanjit Kaur; S. K. Singh; Ajay Arora; Surendra Kumar

2011-01-01

108

Pleiotropy in the melanocortin system: expression levels of this system are associated with melanogenesis and pigmentation in the tawny owl (Strix aluco).  

PubMed

The adaptive function of melanin-based coloration is a long-standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin-based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce ?-melanin-stimulating hormone (?-MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while ?-MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin-based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology. PMID:24033481

Emaresi, Guillaume; Ducrest, Anne-Lyse; Bize, Pierre; Richter, Hannes; Simon, Celine; Roulin, Alexandre

2013-10-01

109

Immune function is related to adult carotenoid and bile pigment levels, but not to dietary carotenoid access during development, in female mallard ducks.  

PubMed

Immune function can be modulated by multiple physiological factors, including nutrition and reproductive state. Because these factors can vary throughout an individual's lifetime as a result of environmental conditions (affecting nutrition) or life-history stage (e.g. entering the adult reproduction stage), we must carefully examine the degree to which developmental versus adult conditions shape performance of the immune system. We investigated how variation in dietary access to carotenoid pigments - a class of molecules with immunostimulatory properties that females deposit into egg yolks - during three different developmental time points affected adult immunological and reproductive traits in female mallard ducks (Anas platyrhynchos). In males and females of other avian species, carotenoid access during development affects carotenoid assimilation ability, adult sexual ornamentation and immune function, while carotenoid access during adulthood can increase immune response and reproductive investment (e.g. egg-laying capacity, biliverdin deposition in eggshells). We failed to detect effects of developmental carotenoid supplementation on adult immune function [phytohemagglutinin-induced cutaneous immune response, antibody production in response to the novel antigen keyhole limpet hemocyanin (KLH), or oxidative burst, assessed by changes in circulating nitric oxide levels], carotenoid-pigmented beak coloration, ovarian development, circulating carotenoid levels or concentration of bile pigments in the gall bladder. However, we did uncover positive relationships between circulating carotenoid levels during adulthood and KLH-specific antibody production, and a negative relationship between biliverdin concentration in bile and KLH-specific antibody production. These results are consistent with the view that adult physiological parameters better predict current immune function than do developmental conditions, and highlight a possible, previously unstudied relationship between biliverdin and immune system performance. PMID:23531827

Butler, Michael W; McGraw, Kevin J

2013-07-15

110

B-Scan and "En-Face" Spectral-Domain Optical Coherence Tomography Imaging for the Diagnosis and Followup of Acute Retinal Pigment Epitheliitis  

PubMed Central

Purpose. To report B-scan and “En-face” spectral-domain optical coherence tomography (SD-OCT) findings in acute retinal pigment epitheliitis (ARPE). Methods. Two patients (3 eyes) with ARPE were examined. Fluorescein and indocyanine green (ICGA) angiography, B-scan, and “En-face” SD-OCT were performed in each patient at initial and follow-up visits. Results. Both patients presented with acute onset of blurred vision, and one with bilateral involvement. B-can OCT revealed disruption of the macular retinal pigment epithelial (RPE) inner band layer and photoreceptors' inner and outer segment (IS-OS) junction. Hyperreflective dots were observed in the outer nuclear layer (ONL) above the RPE/IS-OS disruption. Just around these hyperreflective dots, slight thickening of the hyperreflective IS/OS junction was observed. During the late phase, indocyanine green angiography (ICGA) showed a macular cockade-like hyperfluorescent halo. “En-face” OCT showed the same cockade-like appearance with a hyporeflective center and a hyperreflective border matching the pattern observed on ICGA. At followup, as vision improved without treatment, B-scan OCT demonstrated progressive resolution of the hyperreflective and disrupted lesions; “en-face” OCT also showed disappearance of the macular cockade-like halo with a transient discrete hyperreflective macular star at the RPE level in one eye. Conclusion. “En-face” OCT associated with B-scan SD-OCT analysis appears to be very helpful in the diagnosis and followup of ARPE. The pathophysiology of ARPE remains complex and still poorly understood. These techniques help define the location and extent of structural damage occurring in this disease. PMID:23476659

De Bats, Flore; Wolff, Benjamin; Mauget-Faysse, Martine; Scemama, Claire; Kodjikian, Laurent

2013-01-01

111

In vivo snapshot hyperspectral image analysis of age-related macular degeneration  

PubMed Central

Drusen, the hallmark lesions of age related macular degeneration (AMD), are biochemically heterogeneous and the identification of their biochemical distribution is key to the understanding of AMD. Yet the challenges are to develop imaging technology and analytics, which respect the physical generation of the hyperspectral signal in the presence of noise, artifacts, and multiple mixed sources while maximally exploiting the full data dimensionality to uncover clinically relevant spectral signatures. This paper reports on the statistical analysis of hyperspectral signatures of drusen and anatomical regions of interest using snapshot hyperspectral imaging and non-negative matrix factorization (NMF). We propose physical meaningful priors as initialization schemes to NMF for finding low-rank decompositions that capture the underlying physiology of drusen and the macular pigment. Preliminary results show that snapshot hyperspectral imaging in combination with NMF is able to detect biochemically meaningful components of drusen and the macular pigment. To our knowledge, this is the first reported demonstration in vivo of the separate absorbance peaks for lutein and zeaxanthin in macular pigment. PMID:21096261

Lee, Noah; Wielaard, J.; Fawzi, A. A.; Sajda, P.; Laine, A. F.; Martin, G.; Humayun, M. S.; Smith, R. T.

2014-01-01

112

Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage  

PubMed Central

The retinal pigment epithelial cell (RPE cell) layer protects the photoreceptors of the retina against oxidative stress. The decline of this capacity is believed to be a major factor in the impairment of vision in age-related macular degeneration. Exposure of human adult RPE cells to UV light at predominantly 320–400 nm (UVA light) in the presence of all-trans-retinaldehyde results in photooxidative cytotoxicity. Significant protection of RPE cells was obtained by prior treatment with phase 2 gene inducers, such as the isothiocyanate sulforaphane or a bis-2-hydroxybenzylideneacetone Michael reaction acceptor. The degree of protection was correlated with the potencies of these inducers in elevating cytoprotective glutathione levels and activities of NAD(P)H:quinone oxidoreductase. In embryonic fibroblasts derived from mice in which the genes for the transcription factor Nrf2, the repressor Keap1, or both Nrf2 and Keap1 were disrupted, the magnitude of resistance to photooxidative damage paralleled the basal levels of glutathione and NAD(P)H:quinone oxidoreductase in each cell type. Demonstration of protection of RPE cells against photooxidative damage by induction of phase 2 proteins may shed light on the role of oxidative injury in ocular disease. Moreover, the finding that dietary inducers provide indirect antioxidant protection suggests novel strategies for preventing chronic degenerative diseases, such as age-related macular degeneration. PMID:15229324

Gao, Xiangqun; Talalay, Paul

2004-01-01

113

Intraocular lens iris fixation. Clinical and macular OCT outcomes  

PubMed Central

Background To assess the efficacy, clinical outcomes, visual acuity (VA), incidence of adverse effects, and complications of peripheral iris fixation of 3-piece acrylic IOLs in eyes lacking capsular support. Thirteen patients who underwent implantation and peripheral iris fixation of a 3-piece foldable acrylic PC IOL for aphakia in the absence of capsular support were followed after surgery. Clinical outcomes and macular SD-OCT (Cirrus OCT; Carl Zeiss Meditec, Germany) were analyzed. Findings The final CDVA was 20/40 or better in 8 eyes (62%), 20/60 or better in 12 eyes (92%), and one case of 20/80 due to corneal astigmatism and mild persistent edema. No intraoperative complications were reported. There were seven cases of medically controlled ocular hypertension after surgery due to the presence of viscoelastic in the AC. There were no cases of cystoid macular edema, chronic iridocyclitis, IOL subluxation, pigment dispersion, or glaucoma. Macular edema did not develop in any case by means of SD-OCT. Conclusions We think that this technique for iris suture fixation provides safe and effective results. Patients had substantial improvements in UDVA and CDVA. This surgical strategy may be individualized however; age, cornea status, angle structures, iris anatomy, and glaucoma are important considerations in selecting candidates for an appropriate IOL fixation method. PMID:23050659

2012-01-01

114

Transplantation of Autologous Iris Pigment Epithelium After Removal of Choroidal Neovascular Membranes  

Microsoft Academic Search

Background: Transplantation of autologous iris pig- ment epithelium (IPE) into the subretinal space has been suggested as one approach for the treatment of age-re- lated macular degeneration, as well as for other condi- tions in which loss of retinal pigment epithelium (RPE) occurs. Surgical removal of choroidal neovascular mem- branes is associated with traumatic loss of the RPE cell layer,

Gabriele Thumann; Sabine Aisenbrey; Ulrich Schraermeyer; Bart Lafaut; Peter Esser; Peter Walter; Karl Ulrich Bartz-Schmidt

2000-01-01

115

BEST1 expression in the retinal pigment epithelium is modulated by OTX family members  

Microsoft Academic Search

A number of genes preferentially expressed in the retinal pigment epithelium (RPE) are associated with reti- nal degenerative disease. One of these, BEST1, encodes bestrophin-1, a protein that when mutated causes Best macular dystrophy. As a model for RPE gene regulation, we have been studying the mechanisms that control BEST1 expression, and recently demonstrated that members of the MITF -T

Noriko Esumi; Shu Kachi; Laszlo Hackler Jr; Tomohiro Masuda; Zhiyong Yang; Peter A. Campochiaro; Donald J. Zack

2009-01-01

116

Zinc and Energy Requirements in Induction of Oxidative Stress to Retinal Pigmented Epithelial Cells  

Microsoft Academic Search

In age-related macular degeneration (AMD), retinal pigmented epithelium (RPE) cells are believed to be detrimentally affected. It is thought that zinc may play a part in this process. In the past, therefore, zinc supplementation has been suggested as a treatment for AMD. Experimental data shown here confound this view by indicating that whereas low amounts of zinc do protect RPE

John P. M. Wood; Neville N. Osborne

2003-01-01

117

Idiopathic macular telangiectasia type 2 (idiopathic juxtafoveolar retinal telangiectasis type 2A, Mac Tel 2).  

PubMed

Macular telangiectasia type 2-also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A or Mac Tel 2-is an acquired bilateral neurodegenerative macular disease that usually manifests itself during the fourth to sixth decades of life and is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right-angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV). Optical coherence tomography images typically demonstrate intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic finding is a deep intraretinal hyperfluorescent leakage in the temporal parafoveal area. With time the leakage may involve the whole parafovea, but does not extend to the center of the fovea. Long-term prognosis for central vision is variable and depends on the development of SRNV or macular atrophy. Pathogenesis remains unclear, but Müller cells and macular pigment appear to play a central role. Currently there is no known treatment for the underlying cause of this condition, but treatment of the SRNV may be beneficial. PMID:24160729

Wu, Lihteh; Evans, Teodoro; Arevalo, J Fernando

2013-01-01

118

Bisretinoids of RPE Lipofuscin: Trigger for Complement Activation in Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Genetic association studies and investigations of the constituents of subretinal deposits (drusen) have implicated complement\\u000a dysregulation as one factor predisposing individuals to increased risk of age-related macular degeneration (AMD). Here we\\u000a review evidence that molecular fragments released by photooxidation of the bisretinoids of retinal pigment epithelial lipofuscin,\\u000a can activate complement. Complement activation by this mechanism is dependent on the alternative

Janet R. Sparrow

119

Autosomal Dominant Stargardt-Like Macular Dystrophy  

Microsoft Academic Search

Autosomal dominant Stargardt-like macular dystrophy is one of the early onset macular dystrophies. It is characterized clinically in its early stages by visual loss and by the presence of atrophic macular changes with or without the presence of yellowish flecks. It is an important retinal dystrophy to study, not only because it has implications in the care and treatment of

Larry A Donoso; Albert O Edwards; Arcilee Frost; Tamara Vrabec; Edwin M Stone; Gregory S Hageman; Thomas Perski

2001-01-01

120

Non-invasive in vivo measurement of macular carotenoids  

NASA Technical Reports Server (NTRS)

A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

2009-01-01

121

Pigmented Bowen's disease*  

PubMed Central

Pigmented Bowen's disease is rare, though more prevalent in men. It presents as a well-delineated plaque in areas unexposed to sun. There are reports of association with seborrheic keratosis, solar lentigo or exuberant pigmentation of genital and intertriginous regions. A specific dermoscopy finding is the presence of brown or gray dots in regular arrangement and coiled or dotted vessels. Thus, we aim to raise awareness of the diagnosis of pigmented Bowen's disease in pigmented lesions. PMID:25184929

Mota, Amanda Nascimento Cavalleiro de Macedo; Pineiro-Maceira, Juan; Alves, Maria de Fatima Guimaraes Scotelaro; Tarazona, Monica Jidid Mateus

2014-01-01

122

Macular oedema in idiopathic macular telangiectasia type 1 responsive to aflibercept but not bevacizumab.  

PubMed

We report a patient with macular oedema due to type 1 macular telangiectasia responding to intravitreal aflibercept injection. A 51-year-old man was diagnosed with type 1 idiopathic macular telangiectasia (IMT) in the right eye. The macular oedema was refractory to initial treatment with intravitreal bevacizumab and argon laser photocoagulation. The patient was then treated with intravitreal aflibercept injections, following which the macular oedema was completely resolved and his vision was significantly improved. Intravitreal aflibercept injection appears to improve vision and reduce persistent macular oedema secondary to type 1 IMT and demonstrated promising anatomical and visual outcomes. PMID:25349755

Shibeeb, O'Sam; Vaze, Anagha; Gillies, Mark; Gray, Timothy

2014-01-01

123

Macular Oedema in Idiopathic Macular Telangiectasia Type 1 Responsive to Aflibercept but Not Bevacizumab  

PubMed Central

We report a patient with macular oedema due to type 1 macular telangiectasia responding to intravitreal aflibercept injection. A 51-year-old man was diagnosed with type 1 idiopathic macular telangiectasia (IMT) in the right eye. The macular oedema was refractory to initial treatment with intravitreal bevacizumab and argon laser photocoagulation. The patient was then treated with intravitreal aflibercept injections, following which the macular oedema was completely resolved and his vision was significantly improved. Intravitreal aflibercept injection appears to improve vision and reduce persistent macular oedema secondary to type 1 IMT and demonstrated promising anatomical and visual outcomes.

Shibeeb, O'Sam; Gillies, Mark; Gray, Timothy

2014-01-01

124

The etiology and molecular genetics of human pigmentation disorders  

PubMed Central

Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically normal human pigmentation encompasses a variety of skin and hair color as well as with punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while clinically abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions, often in different cell types. Thus unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, revealing a common cellular origin and/or common genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities is instructive for understanding normal pathways governing development and function of melanocytes. PMID:23799582

Baxter, Laura L.; Pavan, William J.

2012-01-01

125

The effect of soil aeration on superoxide dismutase activity, malondialdehyde level, pigment content and stomatal diffusive resistance in maize seedlings  

Microsoft Academic Search

Deficient soil aeration that causes hypoxia of maize roots frequently decreases plant biomass production. Characterizing relationships among maize physiological responses to varying levels of root hypoxia is critical to predicting maize plant biomass production. Maize seedlings 12 days old were subjected to increasing root hypoxia over a 12 day period by increasing soil water content in 0.06–0.07 m3 m?3 intervals

R. P Bennicelli; D. A Zakrzhevsky; T. I Balakhnina; J Lipiec

1998-01-01

126

Circulating levels and subcutaneous adipose tissue gene expression of pigment epithelium-derived factor in polycystic ovary syndrome and normal women: a case control study  

PubMed Central

Background Polycystic ovary syndrome (PCOS) has been recognized as a metabolic disorder, manifested by abdominal obesity, insulin resistance, dyslipidemia and hypertension. Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor family, is a pleiotropic protein known for its antiangiogenic, antioxidant, and neuroprotective properties and has been shown to induce insulin resistance and play a role in glucose metabolism. Recent studies investigating circulating PEDF levels show elevated serum PEDF in association with insulin resistance in normal-weight women with PCOS, but not in obese PCOS patients. The aims of this study were 1) to assess PEDF gene expression in subcutaneous adipose tissue (scAT) from women with PCOS and nonhirsute, ovulatory controls, and 2) to determine the circulating levels of PEDF in these groups. Methods Total RNA was extracted from adipose tissue biopsy samples and reverse-transcribed to cDNA. Real-time quantitative PCR was performed to determine relative gene expression levels. Results The 22 women with PCOS and 14 non-PCOS controls included in the study had similar age, BMI, and fasting glucose, triglycerides, and HDL-cholesterol levels. Participants with PCOS exhibited higher 2 h oral glucose tolerance test levels (p?=?0.006), total (p?=?0.026) and LDL-cholesterol (p?=?0.036), Ferriman-Gallwey score (p?=?0.003) and total testosterone (p?=?0.001) as compared to controls. BMI-adjusted PEDF serum levels and scAT gene expression were similar in the PCOS and control groups (p?=?0.622 and p?=?0.509, respectively). Circulating PEDF levels were not associated with scAT PEDF gene expression. Multiple regression analysis revealed that, in women with PCOS, insulin contributed positively and significantly to serum PEDF (p = 0.027), independently of testosterone. Conclusion Serum PEDF levels and scAT gene expression were associated with metabolic risk factors, but did not differ between women with PCOS and age- and BMI-matched controls. Circulating levels and scAT gene expression of PEDF were not associated in the study subjects, suggesting additional sources for PEDF in addition to or instead of fat tissue. PMID:23941060

2013-01-01

127

Alterations of retinal pigment epithelium cause AMD-like retinopathy in senescence-accelerated OXYS rats.  

PubMed

Pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the world, remains poorly understood. This makes it necessary to create animal models for studying AMD pathogenesis and to design new therapeutic approaches. Here we showed that retinopathy in OXYS rats is similar to human AMD according to clinical signs, morphology, and vascular endothelium growth factor (VEGF) and pigment epithelium-derived factor (PEDF) genes expression. Clinical signs of retinopathy OXYS rats manifest by the age 3 months against the background of significantly reduced expression level of VEGF and PEDF genes due to the decline of the amount of retinal pigment epithelium (RPE) cells and alteration of choroidal microcirculation. The disruption in OXYS rats' retina starts at the age of 20 days and appears as reduce the area of RPE cells but does not affect their ultrastructure. Ultrastructural pathological alterations of RPE as well as develop forms of retinopathy are observed in OXYS rats from age 12 months and manifested as excessive accumulation of lipofuscin in RPE regions adjacent to the rod cells, whirling extentions of the basement membrane into the cytoplasm. These data suggest that primary cellular degenerative alterations in the RPE cells secondarily lead to choriocapillaris atrophy and results in complete loss of photoreceptor cells in the OXYS rats' retina by the age of 24 months. PMID:21191149

Markovets, Anton M; Saprunova, Valeriya B; Zhdankina, Anna A; Fursova, Anzhella Zh; Bakeeva, Lora E; Kolosova, Natalia G

2011-01-01

128

Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells  

PubMed Central

The retinal pigmented epithelium (RPE) is composed of retinal pigmented epithelial cells joined by tight junctions and represents the outer blood-retinal barrier (BRB). The inner BRB is made of endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows the osmotic gradient and flows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins, and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy incriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools. PMID:24910616

Willermain, Francois; Libert, Sarah; Motulsky, Elie; Salik, Dany; Caspers, Laure; Perret, Jason; Delporte, Christine

2014-01-01

129

From The Cover: A common haplotype in the complement regulatory gene factor H (HF1\\/CFH) predisposes individuals to age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented

Gregory S. Hageman; Don H. Anderson; Lincoln V. Johnson; Lisa S. Hancox; Andrew J. Taiber; Lisa I. Hardisty; Jill L. Hageman; Heather A. Stockman; James D. Borchardt; Karen M. Gehrs; Richard J. H. Smith; Giuliana Silvestri; Stephen R. Russell; Caroline C. W. Klaver; Irene Barbazetto; Stanley Chang; Lawrence A. Yannuzzi; Gaetano R. Barile; John C. Merriam; R. Theodore Smith; Adam K. Olsh; Julie Bergeron; Jana Zernant; Joanna E. Merriam; Bert Gold; Michael Dean; Rando Allikmets

2005-01-01

130

Navigated macular laser decreases retreatment rate for diabetic macular edema: a comparison with conventional macular laser  

PubMed Central

Background The purpose of this study was to evaluate and compare clinical outcomes and retreatment rates using navigated macular laser versus conventional laser for the treatment of diabetic macular edema (DME). Methods In this prospective, interventional pilot study, 46 eyes from 46 consecutive patients with DME were allocated to receive macular laser photocoagulation using navigated laser. Best corrected visual acuity and retreatment rate were evaluated for up to 12 months after treatment. The control group was drawn based on chart review of 119 patients treated by conventional laser at the same institutions during the same time period. Propensity score matching was performed with Stata, based on the nearest-neighbor method. Results Propensity score matching for age, gender, baseline visual acuity, and number of laser spots yielded 28 matched patients for the control group. Visual acuity after navigated macular laser improved from a mean 0.48 ± 0.37 logMAR by a mean +2.9 letters after 3 months, while the control group showed a mean ?4.0 letters (P = 0.03). After 6 months, navigated laser maintained a mean visual gain of +3.3 letters, and the conventional laser group showed a slower mean increase to +1.9 letters versus baseline. Using Kaplan-Meier analysis, the laser retreatment rate showed separation of the survival curves after 2 months, with fewer retreatments in the navigated group than in the conventional laser group during the first 8 months (18% versus 31%, respectively, P = 0.02). Conclusion The short-term results of this pilot study suggest that navigated macular photocoagulation is an effective technique and could be considered as a valid alternative to conventional slit-lamp laser for DME when focal laser photocoagulation is indicated. The observed lower retreatment rates with navigated retinal laser therapy in the first 8 months suggest a more durable treatment effect. PMID:23345966

Neubauer, Aljoscha S; Langer, Julian; Liegl, Raffael; Haritoglou, Christos; Wolf, Armin; Kozak, Igor; Seidensticker, Florian; Ulbig, Michael; Freeman, William R; Kampik, Anselm; Kernt, Marcus

2013-01-01

131

Diabetic Macular Edema: Current and Emerging Therapies  

PubMed Central

Diabetic macular edema is a leading cause of vision impairment among people within the working- age population. This review discusses the pathogenesis of diabetic macular edema and the treatment options currently available for the treatment of diabetic macular edema, including for focal/grid photocoagulation, intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor agents. The biologic rationale for novel therapeutic agents, many of which are currently being evaluated in clinical trials, also is reviewed. PMID:22346109

Wenick, Adam S.; Bressler, Neil M.

2012-01-01

132

[Pathogenesis of age-related macular degeneration].  

PubMed

Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells. PMID:19341030

Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

2009-01-01

133

Molecular pathology of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

2009-01-01

134

Aqueous flare and inflammatory factors in macular edema with central retinal vein occlusion: a case series  

PubMed Central

Background The association of inflammatory factors and the aqueous flare value with macular edema in central retinal vein occlusion (CRVO) patients remains unclear. We investigated the relations between the aqueous flare value and vitreous levels of vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), and interleukin-6 (IL-6) in patients with CRVO and macular edema or patients with idiopathic macular hole (MH). Methods In 38 patients who underwent unilateral vitrectomy (21 CRVO patients and 17 MH patients), vitreous samples were obtained during vitrectomy to measure VEGF, sICAM-1, and IL-6. Retinal ischemia was evaluated from capillary non-perfusion on fluorescein angiography, and the CRVO patients were classified into nonischemic or ischemic groups. Aqueous flare values were measured with a laser flare meter and macular edema was examined by optical coherence tomography. Results The median aqueous flare value increased significantly across the three groups (MH group?levels of VEGF, sICAM-1, and IL-6 in the CRVO group. The flare value was also significantly correlated with the severity of macular edema in the CRVO group. Conclusions Inflammation and/or ischemia may increase vascular permeability and disrupt the blood-aqueous barrier by increasing levels of inflammatory factors in patients with CRVO and macular edema. PMID:24325604

2013-01-01

135

Identification of spectral phenotypes in age-related macular degeneration patients  

NASA Astrophysics Data System (ADS)

The purpose of this study is to show that there exists a spectral characteristic that differentiates normal macular tissue from various types of genetic-based macular diseases. This paper demonstrates statistically that hyperspectral images of macular and other retinal tissue can be used to spectrally differentiate different forms of age-related macular degeneration. A hyperspectral fundus imaging device has been developed and tested for the purpose of collecting hyperspectral images of the human retina. A methodology based on partial least squares and ANOVA has been applied to determine the hyperspectral representation of individual spectral characteristics of retinal features. Each discrete tissue type in the retina has an identifiable spectral shape or signature which, when combined with spatial context, aids in detection of pathological features. Variations in the amount and distribution of various ocular pigments or the inclusion of additional biochemical substances will allow detection of pathological conditions prior to traditional histological presentation. Fundus imaging cameras are ubiquitous and are one of the most common imaging modalities used in documenting a patient's retinal state for diagnosis, e.g. remotely, or for monitoring the progression of an ocular disease. The added diagnostic information obtained with only a minor retro-fit of a specialized spectral camera will lead to new diagnostic information to the clinical ophthalmologist or eye-care specialist.

Davis, Bert; Russell, Steven; Abramoff, Michael; Nemeth, Sheila C.; Barriga, E. Simon; Soliz, Peter

2007-02-01

136

Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV. The BrM of patients with early AMD are characterized by decreased levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithelium-derived factor (PEDF), as well as by degeneration of the elastic layer. Motivated by a previous report that heat increases elastin expression in human skin, we examined the effect of heat on human ARPE-19 cell production of BrM components. Heat treatment stimulated the production of BrM components, including TSP-1, PEDF, and tropoelastin in vitro and increased the antiangiogenic activity of RPE measured in a mouse corneal pocket assay. The effect of heat on experimental CNV was investigated by pretreating the retina with heat via infrared diode laser prior to the induction of CNV. Heat treatment blocked the development of experimental CNV in vivo. These findings suggest that heat treatment may restore BrM integrity and barrier function against new vessel growth.—Sekiyama, E., Saint-Geniez, M., Yoneda, K., Hisatomi, T., Nakao, S., Walshe, T. E., Maruyama, K., Hafezi-Moghadam, A., Miller, J. W., Kinoshita, S., D'Amore, P. A. Heat treatment of retinal pigment epithelium induces production of elastic lamina components and anti-angiogenic activity. PMID:22067481

Sekiyama, Eiichi; Saint-Geniez, Magali; Yoneda, Kazuhito; Hisatomi, Toshio; Nakao, Shintaro; Walshe, Tony E.; Maruyama, Kazuichi; Hafezi-Moghadam, Ali; Miller, Joan W.; Kinoshita, Shigeru; D'Amore, Patricia A.

2012-01-01

137

Hair Follicle Pigmentation  

PubMed Central

Hair shaft melanin components (eu- or/and pheomelanin) are a long-lived record of precise interactions in the hair follicle pigmentary unit, e.g., between follicular melanocytes, keratinocytes, and dermal papilla fibroblasts. Follicular melanogenesis (FM) involves sequentially the melanogenic activity of follicular melanocytes, the transfer of melanin granules into cortical and medulla keratinocytes, and the formation of pigmented hair shafts. This activity is in turn regulated by an array of enzymes, structural and regulatory proteins, transporters, and receptors and their ligands, acting on the developmental stages, cellular, and hair follicle levels. FM is stringently coupled to the anagen stage of the hair cycle, being switched-off in catagen to remain absent through telogen. At the organ level FM is precisely coupled to the life cycle of melanocytes with changes in their compartmental distribution and accelerated melanoblast/melanocyte differentiation with enhanced secretory activity. The melanocyte compartments in the upper hair follicle also provides a reservoir for the repigmentation of epidermis and, for the cyclic formation of new anagen hair bulbs. Melanin synthesis and pigment transfer to bulb keratinocytes are dependent on the availability of melanin precursors, and regulation by signal transduction pathways intrinsic to skin and hair follicle, which are both receptor dependent and independent, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. The important regulators are MC1 receptor its and adrenocorticotropic hormone, melanocyte stimulating hormone, agouti protein ligands (in rodents), c-Kit, and the endothelin receptors with their ligands. Melanin itself has a wide range of bioactivities that extend far beyond its determination of hair color. PMID:15654948

Slominski, Andrzej; Wortsman, Jacobo; Plonka, Przemyslaw M.; Schallreuter, Karin U.; Paus, Ralf; Tobin, Desmond J.

2005-01-01

138

Surgery for full-thickness macular hole in patients with idiopathic macular telangiectasia type 2.  

PubMed

The authors report surgical outcomes of full-thickness macular hole repair in two patients with idiopathic macular telangiectasia in a non-comparative case series. Both patients underwent pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling and injection of 16% C(3)F(8) gas. Patients were imaged with optical coherence tomography (OCT) before and after surgery. The first patient demonstrated macular hole closure on examination and OCT with visual improvement from 20/50 preoperatively to 20/30 after macular hole surgery and subsequent cataract surgery. The second patient's hole closed per OCT immediately after surgery but reopened 4 months later, and visual acuity remained 20/70. Macular hole surgery may be an effective treatment in patients with idiopathic macular telangiectasia and full-thickness macular holes and should be further investigated. PMID:21158375

Gregori, Ninel; Flynn, Harry W

2010-01-01

139

Reduced amplitude and delayed latency in foveal response of multifocal electroretinogram in early age related macular degeneration  

Microsoft Academic Search

AIMTo explore the use of multifocal electroretinograms (MERG) in detecting early changes in age related macular degeneration (AMD).METHOD15 pre-AMD or early AMD eyes showing retinal drusen or irregular fundus pigmentation with window defects by fluorescein angiography (FA) and mildly decreased visual acuity were examined and compared with their asymptomatic fellow eyes. 20 age matched normal eyes were included as controls.

Jodie Li; Mark O M Tso; Tim T Lam

2001-01-01

140

Alcohol and Light-induced Electro-oculographic Responses in Age-related Macular Degeneration & Central Serous Chorioretinopathy  

Microsoft Academic Search

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment\\u000a epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal,\\u000a we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with ‘dry’ and

Kathy H. C. Wu; Michael F. Marmor

2005-01-01

141

Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography  

Microsoft Academic Search

We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results

Bernhard Baumann; Erich Götzinger; Michael Pircher; Harald Sattmann; Christopher Schütze; Ferdinand Schlanitz; Christian Ahlers; Ursula Schmidt-Erfurth; Christoph K. Hitzenberger

2010-01-01

142

Differential Accumulation and Pigmenting Ability of Dietary Carotenoids in Colorful Finches  

E-print Network

484 Differential Accumulation and Pigmenting Ability of Dietary Carotenoids in Colorful Finches carotenoid pigmentation that they use to attract mates. Colorful carotenoid pigments are acquired from sources, it is possible that these pigments are accumulated at different levels in the body and may play

Navara, Kristen

143

Macular degeneration: recent advances and therapeutic opportunities  

Microsoft Academic Search

The central retina mediates high acuity vision, and its progressive dysfunction due to macular degeneration is the leading cause of visual disability among adults in industrialized societies. Here, we summarize recent progress in understanding the pathophysiology of macular degeneration and the implications of this new knowledge for treatment and prevention. The past decade has witnessed remarkable advances in this field,

Amir Rattner; Jeremy Nathans

2006-01-01

144

Bilateral macular hole following myopic photorefractive keratectomy.  

PubMed

A 42-year-old man was admitted to our clinic complaining of visual distortion in his left eye two months after bilateral myopic photorefractive keratectomy (PRK). Macular optical coherence tomography (OCT) showed a stage II macular hole in the left eye. Simultaneous OCT in the right eye showed vitreous traction and distortion of the outer retina. One month later, the patient underwent vitrectomy for the left eye, and the macular hole was closed. Two months after that, the patient complained of visual distortion in the right eye, and OCT revealed increased traction and accentuated outer retinal distortion indicating a stage IB macular hole. Traction attenuated later without any intervention. The short interval between PRK and hole formation, bilateral involvement, and the moderate refractive error in this case highlight the possible role of PRK in aggravating vitreoretinal interface abnormalities. We recommend the addition of PRK to the list of procedures that may be associated with the formation of a macular hole. PMID:24882962

Shoeibi, Nasser; Jabbarpoor Bonyadi, Mohammad Hossein; Abrishami, Majid; Ansari-Astaneh, Mohammad-Reza

2014-06-01

145

Pigment Granule Transport in Chromatophores  

NSDL National Science Digital Library

This resource describes protocols and gives instructional information for carrying out an undergraduate laboratory exercise in vertebrate physiology. Students learn and analyze the dynamics of pigment granule transport in the chromatorphores of fishes. This exercise may be used as a stand alone exercise suitable for lower division undergraduate courses, or may be expanded as a scientific-inquiry based exercise for upper-level undergraduate courses. It includes student outlines, instructor's notes, and suggested questions for laboratory reports.

Kathryn B. Toner (;); Sally E. Nyquist (Bucknell University;)

1997-01-01

146

Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction  

Microsoft Academic Search

Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major compo- nent

Zhongbo Liu; Lijuan Sun; Lu Zhu; Xu Jia; Xuesen Li; Haiqun Jia; Ying Wang; Peter Weber; Jiangang Long; Jiankang Liu

2007-01-01

147

Ranibizumab in diabetic macular edema  

PubMed Central

By 2050 the prevalence of diabetes will more than triple globally, dramatically increasing the societal and financial burden of this disease worldwide. As a consequence of this growth, it is anticipated that there will be a concurrent rise in the numbers of patients with diabetic macular edema (DME), already among the most common causes of severe vision loss worldwide. Recent available therapies for DME target the secreted cytokine, vascular endothelial growth factor (VEGF). This review focuses on the treatment of DME using the first humanized monoclonal antibody targeting VEGF that has been Food and Drug Administration-approved for the use in the eye, ranibizumab (Lucentis®). PMID:24379922

Krispel, Claudia; Rodrigues, Murilo; Xin, Xiaoban; Sodhi, Akrit

2013-01-01

148

Intravitreal bevacizumab for macular edema due to occlusive vasculitis.  

PubMed

Systemic vasculitides can cause retinal vascular pathology, including cotton-wool spots, retinal hemorrhages, vascular occlusion, and capillary nonperfusion. Two main causes of visual decline include macular edema and retinal neovascularization. Presumably, both of these complications are caused by increased intraocular levels of vascular growth and permeability factors. We report a patient with occlusive retinal vasculitis associated with mixed connective tissue disease who was treated with intravitreal bevacizumab for chronic macular edema. One month after treatment, visual acuity improved from 20/80 to 20/60, and foveal thickness decreased from 543 microns to 306 microns. This effect persisted for at least 3 months after treatment. No complications, including increased retinal ischemia, were observed. PMID:17564933

Margolis, Ron; Lowder, Careen Y; Sears, Jonathan E; Kaiser, Peter K

2007-01-01

149

Comparison of mercury levels in various tissues of albino and pigmented mice treated with two different brands of mercury skin-lightening creams  

Microsoft Academic Search

The use of mercury containing skin-lightening creams are becoming increasingly popular among dark-skinned women. The long term use of certain brands may cause serious health effects over the years. In the present study, we investigated the dermal absorption of mercury and its accumulation in the tissues of albino and pigmented mice treated with two brands of mercury containing skin-lightening creams

Iman Al-Saleh; Neptune Shinwari; Inaam El-Doush; Grisellhi Billedo; Mona Al-Amodi; Fathia Khogali

2004-01-01

150

A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is one of the leading cause of blindness among the elderly; however, current therapy options are limited. Epidemiological studies have shown that a diet that is high in ?-3 polyunsaturated (n-3) fatty acids can slow disease progression in patients with advanced AMD. In this study, we evaluated the effect of such a diet on the retinas of Ccl2?/?/Cx3cr1?/? mice, a model that develops AMD-like retinal lesions that include focal deep retinal lesions, abnormal retinal pigment epithelium, photoreceptor degeneration, and A2E accumulation. Ccl2?/?/Cx3cr1?/? mice that ingested a high n-3 fatty acid diet showed a slower progression of retinal lesions compared with the low n-3 fatty acids group. Some mice that were given high levels of n-3 fatty acids had lesion reversion. We found a shunted arachidonic acid metabolism that resulted in decreased pro-inflammatory derivatives (prostaglandin E2 and leukotriene B4) and an increased anti-inflammatory derivative (prostaglandin D2). We also measured lower ocular TNF-? and IL-6 transcript levels in the mice fed a diet of high n-3 fatty acids. Our findings in these mice are in line with human studies of AMD risk reduction by long-chain n-3 fatty acids. This murine model provides a useful tool to evaluate therapies that might delay the development of AMD. PMID:19608872

Tuo, Jingsheng; Ross, Robert J.; Herzlich, Alexandra A.; Shen, Defen; Ding, Xiaoyan; Zhou, Min; Coon, Steven L.; Hussein, Nahed; Salem, Norman; Chan, Chi-Chao

2009-01-01

151

Characteristics of Incident Geographic Atrophy in the Complications of Age-related Macular Degeneration Prevention Trial  

PubMed Central

Objective To characterize the size, location, conformation, and features of incident geographic atrophy (GA) as detected by annual stereoscopic color photographs and fluorescein angiograms (FAs). Design Retrospective cohort study within a larger clinical trial Participants Patients with bilateral large drusen who developed GA during the course of the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Methods Annual stereoscopic color photographs and FAs were reviewed from 114 CAPT patients who developed GA in the untreated eye during 5-6 years of follow-up. Geographic atrophy was defined according to the Revised GA Criteria for identifying early GA23. Color-optimized fundus photographs were viewed concurrently with the FAs during grading. Main Outcome Measures Size and distance from the fovea of individual GA lesions, number of areas of atrophy, and change in visual acuity (VA) when GA first developed in an eye. Results At presentation, the median total GA area was 0.26mm2 (0.1 Disc area). GA presented as a single lesion in 89 (78%) of eyes. The median distance from the fovea was 395?m. Twenty percent of incident GA lesions were subfoveal and an additional 18% were within 250?m of the foveal center. Development of GA was associated with a mean decrease of 7 letters from the baseline visual acuity level compared to 1 letter among matched early age-related macular degeneration (AMD) eyes without GA. GA that formed in areas previously occupied by drusenoid pigment epithelial detachments (DPED) were on average larger (0.53 vs. 0.20 mm2; p=0.0001), more central (50 vs. 500 microns from the center of the fovea; p<0.0001), and associated with significantly worse visual outcome (20/50 vs. 20/25; p=0.0003) than GA with other drusen types as precursors. Conclusions Incident geographic atrophy most often appears on color fundus photographs and fluorescein angiograms as a small, singular, parafoveal lesion, though a large minority of lesions are subfoveal or multifocal at initial detection. The characteristics of incident geographic atrophy vary with precursor drusen types. These data can facilitate design of future clinical trials of therapies for GA. PMID:23622873

Brader, Hilary Smolen; Ying, Gui-shuang; Martin, E. Revell; Maguire, Maureen G.

2013-01-01

152

Common Origin of Pigment Cells  

Microsoft Academic Search

The fundamentally diverse vertebrate pigment cells, melanophores, xanthophores, and iridophores, contain pigmentary organelles known, respectively, as melanosomes, pterinosomes, and reflecting platelets. Their pigments are melanins, pteridines, and purines. Mosaic pigment cells containing more than one type of organelle have been observed and mosaic organelles containing more than one type of pigment have been discovered. It is proposed that the various

Joseph T. Bagnara; Jiro Matsumoto; Wayne Ferris; Sally K. Frost; William A. Turner Jr.; T. T. Tchen; John D. Taylor

1979-01-01

153

Pigment-protein complexes  

SciTech Connect

The photosynthetically-active pigment protein complexes of procaryotes and eucaryotes include chlorophyll proteins, carotenochlorophyll proteins, and biliproteins. They are either integral components or attached to photosynthetic membranes. Detergents are frequently required to solubilize the pigment-protein complexes. The membrane localization and detergent solubilization strongly suggest that the pigment-protein complexes are bound to the membranes by hydrophobic interactions. Hydrophobic interactions of proteins are characterized by an increase in entropy. Their bonding energy is directly related to temperature and ionic strength. Hydrophobic-interaction chromatography, a relatively new separation procedure, can furnish an important method for the purification of pigment-protein complexes. Phycobilisome purification and properties provide an example of the need to maintain hydrophobic interactions to preserve structure and function.

Siegelman, H W

1980-01-01

154

Biologically Active Fibronectin Fragments Stimulate Release of MCP-1 and Catabolic Cytokines from Murine Retinal Pigment Epithelium  

PubMed Central

Purpose High-temperature requirement serine protease (HTRA1) was identified as a candidate age-related macular degeneration gene in multiple genetic studies in humans. To date, no functional studies have shown a mechanism for HTRA1 to instigate ocular tissue abnormalities. In the present study, the authors focused on a substrate of HTRA1, fibronectin, because fibronectin fragments (Fnfs) stimulate biochemical events in other age-related degenerative diseases that are analogous to changes associated with age-related macular degeneration (AMD). The purpose of the study was to determine whether Fnfs stimulate the release of proinflammatory and catabolic cytokines from murine retinal pigment epithelium (RPE). Methods Fibronectin was purified from murine serum by gelatin cross-linked agarose chromatography and subsequently was enzymatically digested with ?-chymotrypsin. The bioactivity of Fnfs was verified by measuring levels of IL-6 and TNF-? in Fnf-exposed murine splenocytes. To analyze the effect of Fnfs on RPE, cytokine and chemokine levels in RPE culture supernatants were assayed by ELISA. Results IL-6 and TNF-? proinflammatory cytokines were released from primary murine splenocytes in proportion to the dose and length of Fnf treatment, indicating that ?-chymotryptic digests of fibronectin are biologically active. Fnf treatment of murine RPE cells stimulated the release of microgram and nanogram levels of IL-6, MMP-3, MMP-9, and MCP-1, whereas only picogram levels were detected in untreated cells. Conclusions Fnfs stimulate the release of proinflammatory cytokines, matrix metalloproteinases, and monocyte chemoattractant protein from murine RPE cells. This observation indicated that Fnfs could contribute to ocular abnormalities by promoting inflammation, catabolism, and monocyte chemoattraction. PMID:19151387

Austin, Bobbie Ann; Liu, Baoying; Li, Zhuqing; Nussenblatt, Robert B.

2009-01-01

155

Cigarette Smoke-Related Hydroquinone Dysregulates MCP-1, VEGF and PEDF Expression in Retinal Pigment Epithelium in Vitro and in Vivo  

Microsoft Academic Search

BackgroundAge-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly population. Debris (termed drusen) below the retinal pigment epithelium (RPE) have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV). The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking,

Marianne Pons; Maria E. Marin-Castaño; Carlo Gaetano

2011-01-01

156

Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration  

Microsoft Academic Search

A primary feature of age-related macular degeneration (AMD) is the presence of extracellular deposits between the retinal pigment epithelium (RPE) and underlying Bruch's membrane, leading to RPE dysfunction, photoreceptor death and severe visual loss. AMD accounts for about 50% of blind registrations in Western countries and is a common, genetically complex disorder. Very little is known regarding its molecular basis.

Caroline Hayward; Xinhua Shu; Artur V. Cideciyan; Alan Lennon; Perdita Barran; Sepideh Zareparsi; Lindsay Sawyer; Grace Hendry; Baljean Dhillon; Ann H. Milam; Philip J. Luthert; Anand Swaroop; Nicholas D. Hastie; Samuel G. Jacobson; Alan F. Wright

2003-01-01

157

Diode laser photocoagulation for diabetic macular oedema.  

PubMed Central

AIMS--This study aimed to investigate whether diode laser irradiation, which is poorly absorbed by haemoglobin, can induce closure of leaking retinal microvascular lesions in the treatment of diabetic macular oedema. METHODS--Thirty three eyes with clinically significant diabetic macular oedema were treated with a diode laser. Fundus evaluation before and after treatment included visual acuity, stereoscopic biomicroscopy, colour photographs, and fluorescein angiography. RESULTS--At a mean period of review of 6 months macular oedema had completely or partially resolved in 27 eyes. Visual acuity improved in three, deteriorated in one, and was unchanged in 29 eyes. CONCLUSION--Preliminary data suggest that diode laser therapy induces closure of leaking retinal microaneurysms and is effective in the treatment of diabetic macular oedema. Images PMID:7742274

Ulbig, M W; McHugh, D A; Hamilton, A M

1995-01-01

158

Unilateral Idiopathic Macular Telangiectasia with Choroidal Neovascularization.  

PubMed

A 40-year-old man with decreasing visual acuity in his left eye over 1 year, diagnosed elsewhere as vein occlusion and treated unsuccessfully by systemic steroids was reported. Retrospective analysis of available previous imaging studies was undertaken, and a retrospective diagnosis of idiopathic macular telangiectasia (IMT) was made. Examination revealed subfoveal neovascularization and retinochoroidal anastomosis (RCA) in his left eye with macular edema and exudates surrounding it. The right eye was normal. Current fluorescein angiography (FA) confirmed the presence of choroidal neovascularization and RCA, and optical coherence tomography (OCT) demonstrated cystoid macular edema and subfoveal neovascularization.The patient was diagnosed with unilateral idiopathic macular telangiectasia complicated by subretinal neovascularization. The presences of a choroidal neovascularization process and an RCA have not, to our knowledge, been reported in this type of IMT. PMID:20337307

Mezad-Koursh, Daphna; Zayit-Soudry, Shiri; Barak, Adiel; Loewenstein, Anat

2010-03-01

159

Combination Therapy for Diabetic Macular Edema  

PubMed Central

Diabetic macular edema is a main reason for visual loss in diabetic patients. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenetic process of DME gave reason for intravitreal treatment with corticosteroids. The introduction of anti-VEGF drugs brought a revolutionary change in the treatment of DME. This paper will review the important clinical trials with an emphasis on combination therapies. PMID:22523648

Zur, Dinah; Loewenstein, Anat

2012-01-01

160

[Pathophysiology of macular diseases--morphology and function].  

PubMed

Ophthalmic fundus imaging plays an important role in the advances in the pathophysiology of retinal diseases. Using fundus imaging, we studied morphological changes in the choroid, subretinal pathophysiology and photoreceptor and retinal pigment epithelial (RPE) cell damage, and functional abnormalities of photoreceptor cells in macular diseases. To evaluate the choroidal changes, we performed enhanced depth imaging optical coherence tomography (EDI-OCT) for macular diseases. Choroidal thickness both in the affected eyes and in the fellow eyes with choroidal vascular hyperpermeability was thicker in patients with central serous chorioretinopathy (CSC). Photodynamic therapy (PDT) reduced the hyperpermeability and led to choroidal thinning in eyes with CSC, whereas laser photocoagulation did not result in any change in choroidal thickness, suggesting different mechanism of action for these two forms of treatment. PDT also decreased choroidal thickness in eyes with polypoidal choroidal vasculopathy. These findings will help to elucidate the pathophysiologic features of CSC as well as responses to treatment. Patients with acute Vogt-Koyanagi-Harada (VKH) disease have markedly thickened choroids. Both the choroidal thickness and the retinal detachment in these patients decreased quickly with corticosteroid treatment. EDI-OCT can be used to evaluate the choroidal involvement in VKH disease in acute stages and may prove useful in the diagnosis and management of this disease. Dome-shaped macula is the result of a localized thickening of the sclera under the macula in highly myopic patients, and it cannot be categorized into any known type of staphyloma. EDI-OCT is helpful in monitoring the proposed site of pathophysiologic changes in the choroid and the sclera, and provides noninvasively information not available by other means. To clarify the subretinal changes and the mechanism of cell damage in macular detachment, we studied the clinical characteristics of yellow deposits (multiple dot-like yellow precipitates and subretinal yellow material) seen in CSC using fundus autofluorescence and OCT. The yellow deposits had highly reflective tissue in the intraretinal and subretinal spaces seen on OCT and hyperfluorescence on short-wave autofluorescence (SW-AF) examinations during the follow-up period. These findings may indicate that formations of yellow deposits are associated with the accumulation of the photoreceptor outer segments and metabolism and phagocytosis by macrophages or RPE cells. SW-AF also demonstrated a hypofluorescence corresponding to the accumulated areas of yellow deposits during the long term followup period. Another study using infrared autofluorescence examination demonstrated that the yellow deposits induced a decrease in melanin and the functional decline of RPE cells in CSC. These may indicate that the existence of depositions in eyes with CSC is associated with photoreceptor and RPE cells damage. Similar yellow deposits can also be seen in eyes with macular detachment, e. g. branch retinal vein occlusion. We report a new method of retinal densitometry using SW-AF examination by scanning laser ophthalmoscope. We named the technique autofluorescence densitometry (AFD). This technique can evaluate photopigment density from serial SW-AF images during exposure to excitation light. This new technique can examine a much broader macular area and create a distribution map of optical density of the photopigments. It is also easy to compare the distribution of the photopigment densities with other retinal imaging devices such as OCT. To investigate functional abnormalities in eyes with CSC, we measured the optical density of the photopigments using AFD in both the acute and quiescent phase. The photopigment density decreased at the serous retinal detachment. The density remained decreased immediately after resolution and showed delayed recovery. The photopigments decreased even in eyes with a morphologic recovery of the outer retina. AFD could identify the functional impairment of the outer retina as characterized by

Iida, Tomohiro

2011-03-01

161

Ranibizumab: in diabetic macular oedema.  

PubMed

Ranibizumab, an intravitreally administered inhibitor of vascular endothelial growth factor (VEGF), is approved for the treatment of visual impairment associated with diabetic macular oedema (DME) in the EU. In four well designed, phase II or III trials (RESOLVE, RESTORE, RIDE and RISE), 1-2 years' treatment with ranibizumab was more effective than sham or focal/grid laser therapy in improving best corrected visual acuity (BCVA) and reducing central retinal thickness (CRT) in patients with visual impairment associated with DME. Additionally, in two well designed phase III trials (RESTORE and DRCR.net-1), 1 year of treatment with ranibizumab as an adjunct to laser therapy was more effective than laser monotherapy in improving BCVA and CRT in patients with visual impairment associated with DME. Improvements in BCVA with ranibizumab alone or as an adjunct to laser therapy were observed at the first follow-up visits in these studies (i.e. 1-4 weeks after the start of treatment), and were associated with gains in vision-related quality of life, as assessed using the National Eye Institute Visual Functioning Questionnaire-25. The ocular and non-ocular adverse event profile of ranibizumab in patients with DME is similar to that observed in patients with neovascular (wet) age-related macular degeneration or retinal vein occlusion. Based on tolerability data from clinical trials, there is no indication that ranibizumab alone or combined with laser is associated with an increased risk of cardiovascular or cerebrovascular events potentially related to systemic VEGF inhibition. PMID:22356289

Frampton, James E

2012-03-01

162

Optical coherence tomographic findings at the fixation point in a case of bilateral congenital macular coloboma  

PubMed Central

Background Congenital macular coloboma is a rare ocular disease that consists of atrophic lesions in the macula with well-circumscribed borders. We report the findings of spectral domain optical coherence tomography (SD-OCT) at the fixation point in a case of bilateral macular coloboma. Case report The subject is a 4-year-old boy. He visited our hospital at age 1 year and 4 months for the evaluation of strabismus. The fundus examination of both eyes showed round-shaped sharply-demarcated atrophic lesions involving the macula with large choroidal vessels and bared sclera at the base. Immunologic tests including toxoplasmosis, rubella, varicella, herpes virus, and human T-cell leukemia virus were all negative. At age 4 years and 1 month, cycloplegic refraction showed insignificant refractive errors and his best corrected visual acuity was 0.6 bilaterally. The SD-OCT showed a crater-like depression accompanying atrophic neurosensory retina, and the absence of retinal pigment epithelium and choroid. Examination of the fixation behavior by visuscope showed steady fixation with an area 0.5° nasal to the nasal edge of the atrophic lesion bilaterally. The SD-OCT findings at fixation area showed remaining normal retinal structures involving inner segment-outer segment (IS/OS) junction line. Conclusion The findings of SD-OCT have been shown to be useful in the diagnosis of macular coloboma. In the fixation point, the structure of retina and choroid were well preserved. PMID:24899799

Abe, Kosuke; Shirane, Jumi; Sakamoto, Masuo; Tanabe, Fumi; Kuniyoshi, Kazuki; Matsumoto, Chota; Shimomura, Yoshikazu

2014-01-01

163

Two siblings with late-onset cone-rod dystrophy and no visible macular degeneration  

PubMed Central

Background We report our findings in two siblings with late-onset cone–rod dystrophy (CRD) with no visible macular degeneration. Cases and methods Case 1 was an 82-year-old man who first noticed a decrease in vision and color blindness in his early seventies. His mother and younger sister also had visual disturbances. His decimal visual acuity was 0.3 in the right eye and 0.2 in the left eye. Ophthalmoscopy showed normal fundi, and fluorescein angiography was also normal in both eyes. The photopic single flash and flicker eletroretinograms (ERGs) were severely attenuated and the scotopic ERGs were slightly reduced in both eyes. Case 2 was the 80-year-old younger sister of Case 1. She first noticed a decline in vision and photophobia in both eyes in her early seventies. Her decimal visual acuity was 0.4 in the right eye and 0.2 in the left eye. Ophthalmoscopy showed mottling of the retinal pigment epithelium in the midperiphery with no visible macular degeneration. The photopic single flash and flicker ERGs were severely attenuated, and the scotopic ERGs were slightly reduced in both eyes. Conclusion These siblings are the oldest reported cases of CRD with no visible macular degeneration. Thus, CRD should be considered in patients with reduced visual acuity, color blindness, and photophobia even if they are older than 70 years. PMID:24039390

Sakuramoto, Hiroyuki; Kuniyoshi, Kazuki; Tsunoda, Kazushige; Akahori, Masakazu; Iwata, Takeshi; Shimomura, Yoshikazu

2013-01-01

164

Pigment chemistry and colour of Pelargonium flowers  

Microsoft Academic Search

The major factors responsible for colour variation in a range of Pelargonium species and cultivars were shown to be the types and relative levels of pigments present. Variations in pH and copigment levels were not found to contribute significantly. Flowers with colours ranging from cream and pink through to deep purple, including salmon, orange and red, were studied. While either

Kevin A. Mitchell; Kenneth R. Markham; Murray R. Boase

1998-01-01

165

Induction of vascular endothelial growth factor by 4-hydroxynonenal and its prevention by glutathione precursors in retinal pigment epithelial cells.  

PubMed

Although 4-hydroxynonenal, a highly reactive lipid peroxidation product, is implicated in several age-related disorders such as Alzheimer's and Parkinson's diseases, its role in age-related macular degeneration is not known. The purpose of this study was to determine whether 4-hydroxynonenal increases vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial cells (ARPE-19), a source of VEGF in choroidal neovascularization observed in age-related macular degeneration. In addition, it was the purpose of this study to assess whether glutathione (GSH) and GSH precursors can inhibit the effects of 4-hydroxynonenal. At 1 micro M, 4-hydroxynonenal did not alter cell viability, but elevated VEGF secretion and mRNA expression by 35% (p<0.05) and 1.9-fold (p<0.05), respectively. However, at concentrations 5 microM and above, 4-hydroxynonenal reduced VEGF secretion as well as cell viability. At 1 and 10 microM, 4-hydroxynonenal did not induce apoptosis in ARPE-19 cells. 4-Hydroxynonenal (1 microM) reduced intracellular GSH by 25% (p<0.05) and increased oxidative stress by 50% (p<0.05). GSH precursor pretreatment for 1 h, which increased intracellular GSH levels by 50% (p<0.05), as well as GSH co-treatment, inhibited the VEGF-inductive and cytotoxic effects of 4-hydroxynonenal. Thus, 4-hydroxynonenal (1 microM) induces VEGF expression and secretion in ARPE-19 cells. This effect is likely due to GSH depletion and an associated increase in intracellular oxidative stress, resulting in increased VEGF mRNA levels. 4-Hydroxynonenal-mediated VEGF secretion as well as cytotoxicity can be reversed with GSH precursor pretreatment or GSH co-treatment. PMID:12167462

Ayalasomayajula, Surya P; Kompella, Uday B

2002-08-01

166

Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats.  

PubMed

Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy. PMID:22683466

Kolosova, Nataliya G; Muraleva, Natalia A; Zhdankina, Anna A; Stefanova, Natalia A; Fursova, Anzhela Z; Blagosklonny, Mikhail V

2012-08-01

167

Broiler skin pigmentation based on bioavailability of specific oxycarotenoid pigments  

E-print Network

BROILER SKIN PIGMENTATION BASED ON BIOAVAILABILITY OF SPECIFIC OXYCAROTENOID PIGMENTS A Thesis by DAVID ANGEL GANBOA GARCIA Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements... for the degree of MASTER OF SCIENCE August 1992 Major Subject: Nutrition BROILER SKIN PIGMENTATION BASED ON BIOAVAILABILITY OP SPECIFIC OXYCAROTENOID PIGMENTS A Thesis by DAVID ANGEL GAMBOA GARCIA Approved as to style and content by: C. A. Bai, ley...

Gamboa Garcia, David Angel

2012-06-07

168

The historical discovery of macular edema.  

PubMed

The occurrence of macular edema, or of intraretinal fluid in general, was largely unknown prior to the invention of the ophthalmoscope. One of the first reports on 'Retinitis in Glycosuria', a disease complex, which today would partly be described as diabetic maculopathy, was published in 1856 by Jaeger. His observations were confirmed less than twenty years later by Nettleship in London, and in 1875 Appolinaire Bouchardat from Paris described fluid and lipid accumulation in the macula which led--in his words--to a glucose induced amblyopia. The first pathophysiological hypotheses of fluid accumulation in the posterior pole were then put forward in 1882 by Tartuferi, who thought the edema represented swelling of photoreceptor sheaths. In 1896, the Frenchman Nuel coined the term 'oedème maculaire' which he had observed in a retinitis pigmentosa patient. However, it was not until the end of the first World War, that the Swiss ophthalmologist Alfred Vogt observed macular edema in a variety of other ocular conditions such as iridocyclitiOFF macular edema to a macular hole. A quarter of a century later Bangerter coined the German term 'Zystoides Makulaödem', and in 1950, Hruby was the first to draw attention to the development of macular edema after cataract extraction. Three years later this was followed by Irvine's classical paper on cystoid macular edema after intra- and extracapsular cataract extraction which had been complicated by incarceration of the vitreous in the anterior segment with consecutive tugging on the macula. A decade later, the phenomenon of cystic fluid accumulation in the macula after cataract extraction was further characterised by Gass and Norton using fluorescein angiography. The ensuing years saw the emergence of new concepts regarding the blood-retinal barrier and the paramount role of its dysfunction in the development of macular edema. PMID:10896334

Wolfensberger, T J

1999-01-01

169

Interaction of Complement Factor H and Fibulin3 in Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a major cause of vision loss. It is associated with development of characteristic plaque-like deposits (soft drusen) in Bruch’s membrane basal to the retinal pigment epithelium (RPE). A sequence variant (Y402H) in short consensus repeat domain 7 (SCR7) of complement factor H (CFH) is associated with risk for “dry” AMD. We asked whether the eye-targeting of this disease might be related to specific interactions of CFH SCR7 with proteins expressed in the aging human RPE/choroid that could contribute to protein deposition in drusen. Yeast 2-hybrid (Y2H) screens of a retinal pigment epithelium/choroid library derived from aged donors using CFH SCR7 baits detected an interaction with EFEMP1/Fibulin 3 (Fib3), which is the locus for an inherited macular degeneration and also accumulates basal to macular RPE in AMD. The CFH/Fib3 interaction was validated by co-immunoprecipitation of native proteins. Quantitative Y2H and ELISA assays with different recombinant protein constructs both demonstrated higher affinity for Fib3 for the disease-related CFH 402H variant. Immuno-labeling revealed colocalization of CFH and Fib3 in globular deposits within cholesterol-rich domains in soft drusen in two AMD donors homozygous for CFH 402H (H/H). This pattern of labeling was quite distinct from those seen in examples of eyes with Y/Y and H/Y genotypes. The CFH 402H/Fib3 interaction could contribute to the development of pathological aggregates in soft drusen in some patients and as such might provide a target for therapeutic intervention in some forms of AMD. PMID:23840815

Wyatt, M. Keith; Tsai, Jen-Yue; Mishra, Sanghamitra; Campos, Maria; Jaworski, Cynthia; Fariss, Robert N.; Bernstein, Steven L.; Wistow, Graeme

2013-01-01

170

Claudin-19 and the Barrier Properties of the Human Retinal Pigment Epithelium  

PubMed Central

Purpose. The retinal pigment epithelium (RPE) separates photoreceptors from choroidal capillaries, but in age-related macular degeneration (AMD) capillaries breach the RPE barrier. Little is known about human RPE tight junctions or the effects of serum on the retinal side of the RPE. Methods. Cultured human fetal RPE (hfRPE) was assessed by the transepithelial electrical resistance (TER) and the transepithelial diffusion of methylated polyethylene glycol (mPEG). Claudins and occludin were monitored by quantitative RT-PCR, immunoblotting, and immunofluorescence. Results. Similar to freshly isolated hfRPE, claudin-19 mRNA was 25 times more abundant than claudin-3. Other detectable claudin mRNAs were found in even lesser amounts, as little as 3000 times less abundant than claudin-19. Claudin-1 and claudin-10b were detected only in subpopulations of cells, whereas others were undetectable. Knockdown of claudin-19 by small interfering RNA (siRNA) eliminated the TER. siRNAs for other claudins had minimal effects. Serum affected tight junctions only when presented to the retinal side of the RPE. The TER increased 2 times, and the conductance of K+ relative to Na+ decreased without affecting the permeability of mPEG. These effects correlated with increased steady-state levels of occludin. Conclusions. Fetal human RPE is a claudin-19–dominant epithelium that has regional variations in claudin-expression. Apical serum decreases RPE permeability, which might be a defense mechanism that would retard the spread of edema due to AMD. PMID:21071746

Peng, Shaomin; Rao, Veena S.; Adelman, Ron A.

2011-01-01

171

Pigments in avocado tissue and oil.  

PubMed

Pigments are important contributors to the appearance and healthful properties of both avocado fruits and the oils extracted from these fruits. This study determined carotenoid and chlorophyll pigment concentrations in the skin and three sections of the flesh (outer dark green, middle pale green, and inner yellow flesh-nearest the seed) and anthocyanin concentrations in the skin of Hass avocado during ripening at 20 degrees C. Pigments were extracted from frozen tissue with acetone and measured using high-performance liquid chromatography. Pigments were also measured in the oil extracted from freeze-dried tissue sections by an accelerated solvent extraction system using hexane. Carotenoids and chlorophylls identified in the skin, flesh, and oil were lutein, alpha-carotene, beta-carotene, neoxanthin, violaxanthin, zeaxanthin, antheraxanthin, chlorophylls a and b, and pheophytins a and b with the highest concentrations of all pigments in the skin. Chlorophyllides a and b were identified in the skin and flesh tissues only. As the fruit ripened and softened, the skin changed from green to purple/black, corresponding to changes in skin hue angle, and a concomitant increase in cyanidin 3-O-glucoside and the loss of chlorophyllide a. In flesh tissue, chroma and lightness values decreased with ripening, with no changes in hue angle. The levels of carotenoids and chlorophylls did not change significantly during ripening. As fruit ripened, the total chlorophyll level in the oil from the flesh sections remained constant but declined in the oil extracted from the skin. PMID:17177553

Ashton, Ofelia B O; Wong, Marie; McGhie, Tony K; Vather, Rosheila; Wang, Yan; Requejo-Jackman, Cecilia; Ramankutty, Padmaja; Woolf, Allan B

2006-12-27

172

Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration.  

PubMed

Zinc (Zn) is abundantly enriched in sub-retinal pigment epithelial (RPE) deposits, the hallmarks of age-related macular degeneration (AMD), and is thought to play a role in the formation of these deposits. However, it is not known whether Zn is the only metal relevant for sub-RPE deposit formation. Because of their involvement in the pathogenesis of AMD, we determined the concentration and distribution of calcium (Ca), iron (Fe) and copper (Cu) and compared these with Zn in isolated and sectioned macular (MSD), equatorial (PHD) and far peripheral (FPD) sub-RPE deposits from an 86 year old donor eye with post mortem diagnosis of early AMD. The sections were mounted on Zn free microscopy slides and analyzed by microprobe synchrotron X-ray fluorescence (?SXRF). Metal concentrations were determined using spiked sectioned sheep brain matrix standards, prepared the same way as the samples. The heterogeneity of metal distributions was examined using pixel by pixel comparison. The orders of metal concentrations were Ca ? Zn > Fe in all three types of deposits but Cu levels were not distinguishable from background values. Zinc and Ca were consistently present in all deposits but reached highest concentration in MSD. Iron was present in some but not all deposits and was especially enriched in FPD. Correlation analysis indicated considerable variation in metal distribution within and between sub-RPE deposits. The results suggest that Zn and Ca are the most likely contributors to deposit formation especially in MSD, the characteristic risk factor for the development of AMD in the human eye. PMID:24740686

Flinn, Jane M; Kakalec, Peter; Tappero, Ryan; Jones, Blair; Lengyel, Imre

2014-07-01

173

Macular microcirculation in cystoid maculopathy of diabetic patients  

Microsoft Academic Search

BACKGROUND--In patients with diabetic macular oedema and central cysts ischaemia of the retina appears to be an important contributing factor in the pathogenesis of cysts. This study was performed to further elucidate the role of the inner retinal microcirculation in diabetic cystoid macular oedema (CMO). METHODS--Video fluorescein angiography allows visualisation of the macular microvasculature and measurements of the capillary blood

O Arend; A Remky; A Harris; B Bertram; M Reim; S Wolf

1995-01-01

174

Pigmentation of Crt Phosphors  

NASA Astrophysics Data System (ADS)

To improve the contrast of a TV screen, not only the phosphor brightness, but also the daylight reflectivity of a screen has to be considered. The relation of contrast on the one hand and luminance, as well as reflectivity on the other hand, can be quantified by the Luminance-Contrast-Performance (LCP): [ LCP = frac {Luminance}{sqrt Diffuse reflectance} ] In order to reduce the reflectivity of the white phosphor powders (e.g. ZnS:Ag,Al, Y2O2S:Eu), each individual phosphor particle is covered with a pigment. The pigment colour should correspond to the emission of the respective type of phosphor, for instance, CoAl2O4 for blue emitting ZnS:Ag,Al or Fe2O3 for for red emitting Y2O2S:Eu. The pigment particles (e.g. CoAl2O4, Fe2O3) have to be quite small in size (80 to 120 nm) to guarantee a sufficient adhesion on the phosphor particles. In addition, other ingredients like inorganic oxides or organic polymers can be required to achieve a good adhesion and to establish a homogeneous thin layer of pigment particles on the phosphor surface.

Feldmann, Claus Clemens

2001-11-01

175

Kinetics of central macular thickness reduction in patients with macular edema after intravitreal drug therapy  

PubMed Central

Background The purpose of this study was to characterize central macular thickness and retinal volume following intravitreal injections using time domain and spectral domain optical coherence tomography (TD-OCT and SD-OCT, respectively). Methods Nine patients with macular edema secondary to diabetes or retinal vein occlusion treated with intravitreal triamcinolone 4.0 mg and/or bevacizumab 1.25 mg were enrolled. Central macular thickness and volume was measured by SD-OCT and TD-OCT scan at baseline, and 1, 3, 6, 24, 48 hours, and 1 week postinjection. Results Equations were derived to describe central macular thickness and volume reduction in the hours following intravitreal injection. Measurements of central macular thickness by SD-OCT were significantly reduced by 3 hours (P = 0.03) and retinal volume by 6 hours (P = 0.03). Central macular thickness measured 40.9 (28.6–53.2) ?m thicker on the SD-OCT instrument while volume measured 3.47 (3.27–3.66) mm3 higher. Conclusion Significant central macular thickness and volume reductions occur in the first hours after injection with triamcinolone and/or bevacizumab. PMID:22205836

He, Lingmin; Chan, Annie; Leng, Theodore; Blumenkranz, Mark S

2011-01-01

176

VEGF polymorphisms are associated with neovascular age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. Linkage has been shown to the vascular endothelial growth factor (VEGF) gene and ocular levels of VEGF are raised in individuals with the neovascular form of disease. To examine the role of VEGF further, we conducted a case-c ontrol study where 45 individuals with neovascular AMD

Amanda J. Churchill; James G. Carter; Helen C. Lovell; Conor Ramsden; Steven J. Turner; Anna Yeung; Julia Escardo; Denize Atan

2006-01-01

177

Diabetic macular edema: New promising therapies  

PubMed Central

The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

2013-01-01

178

Structural changes in individual retinal layers in diabetic macular edema.  

PubMed

Optical coherence tomography (OCT) has enabled objective measurement of the total retinal thickness in diabetic macular edema (DME). The central retinal thickness is correlated modestly with visual impairment and changes paradoxically after treatments compared to the visual acuity. This suggests the clinical relevance of the central retinal thickness in DME and the presence of other factors that affect visual disturbance. Recent advances in spectral-domain (SD) OCT have provided better delineation of the structural changes and fine lesions in the individual retinal layers. Cystoid spaces in the inner nuclear layer and outer plexiform layer are related to quantitative and qualitative parameters in fluorescein angiography. OCT often shows vitreoretinal interface abnormalities in eyes with sponge-like retinal swelling. Serous retinal detachment is sometimes accompanied by hyperreflective foci in the subretinal fluid, which exacerbates the pathogenesis at the interface of the photoreceptors and retinal pigment epithelium. Photoreceptor damage at the fovea is thought to be represented by disruption of the external limiting membrane or the junction between the inner and outer segment lines and is correlated with visual impairment. Hyperreflective foci in the outer retinal layers on SD-OCT images, another marker of visual disturbance, are associated with foveal photoreceptor damage. PMID:24073417

Murakami, Tomoaki; Yoshimura, Nagahisa

2013-01-01

179

Structural Changes in Individual Retinal Layers in Diabetic Macular Edema  

PubMed Central

Optical coherence tomography (OCT) has enabled objective measurement of the total retinal thickness in diabetic macular edema (DME). The central retinal thickness is correlated modestly with visual impairment and changes paradoxically after treatments compared to the visual acuity. This suggests the clinical relevance of the central retinal thickness in DME and the presence of other factors that affect visual disturbance. Recent advances in spectral-domain (SD) OCT have provided better delineation of the structural changes and fine lesions in the individual retinal layers. Cystoid spaces in the inner nuclear layer and outer plexiform layer are related to quantitative and qualitative parameters in fluorescein angiography. OCT often shows vitreoretinal interface abnormalities in eyes with sponge-like retinal swelling. Serous retinal detachment is sometimes accompanied by hyperreflective foci in the subretinal fluid, which exacerbates the pathogenesis at the interface of the photoreceptors and retinal pigment epithelium. Photoreceptor damage at the fovea is thought to be represented by disruption of the external limiting membrane or the junction between the inner and outer segment lines and is correlated with visual impairment. Hyperreflective foci in the outer retinal layers on SD-OCT images, another marker of visual disturbance, are associated with foveal photoreceptor damage. PMID:24073417

Yoshimura, Nagahisa

2013-01-01

180

Macular injury by an Nd:YAG rangefinder  

NASA Astrophysics Data System (ADS)

The authors report the clinical findings of a civilian patient who unintentionally looked into the laser beam of a British range finder, obtained on the black market. The patient was investigated by fluorescein angiography. Indocyanine green angiography (ICG) and microperimetry both in the acute stage (2 hours) and four weeks later. Hundred mg prednisone tapered over 9 days was prescribed. Additionally 50 ?g tissue plasminogen activator (TPA) and 0.5 ml pure C2F6 were injected in the vitreous. In the acute phase hemorrhage was located beneath the retina, primarily beneath the retinal pigment epithelium. Retinal defects as seen initially over the subretinal blood, were reduced after four weeks, but a retinal defect ranging from the lasered site towards the fovea remained. Visual acuity slightly increased from 20/100 to 20/63. ICG showed a large hypofluorescent spot in the macula. The technical parameters of the range finder were: Nd:YAG laser (1064 nm), pulse duration 10 ns, beam divergence 1.5 mrad, energy 10 mJ. A range finder can produce severe macular injury. The primary laser tissue interaction mechanism seems to be explosive disruption of choroidal tissue. Intravitral injection of TPA and C2F6 may be an adjunct in the therapy of acute laser lesions. A late complication can be secondary choroidal neovascularization.

Roider, Johann; Buesgen, Patrick; Hoerauf, Hans; Laqua, Horst; Birngruber, Reginald

1999-06-01

181

Comparison of A2E Cyto- and Phototoxicity with all-trans-Retinal in Human Retinal Pigment Epithelial Cells†  

PubMed Central

All-trans-retinal is the precursor of A2E, a fluorophore within lipofuscin, which accumulates in human retinal pigment epithelial (hRPE) cells and contributes to age-related macular degeneration. Here we have compared the in vitro dark cytotoxicity and visible-light-mediated photoreactivity of all-trans-retinal and A2E in hRPE cells. All-trans-retinal caused distinct cytotoxicity in hRPE cells measured with MTS and LDH assays. Significant increases in intracellular oxidized glutathione (GSSG), extracellular GSH and GSSG levels and lipid hydroperoxide production were observed in cells incubated in the dark with 25 and 50 ?M all-trans-retinal. Light modified all-trans-retinal's harmful action and decreased extracellular glutathione and hydroperoxide levels. A2E (<25 ?M) did not affect cell metabolism or cytoplasmic membrane integrity in the dark or when irradiated. 25 ?M A2E raised the intracellular GSSG level in hRPE cells to a much smaller extent than 25 ?M all-trans-retinal. A2E did not induce glutathione efflux or hydroperoxide generation in the dark or after irradiation. These studies support our previous conclusions that although A2E may be harmful at high concentrations or when oxidized, its phototoxic properties are insignificant compared to those of all-trans-retinal. The endogenous production of A2E may serve as a protective mechanism to prevent damage to the retina by free all-trans-retinal. PMID:20497365

Wielgus, Albert R.; Chignell, Colin F.; Ceger, Patricia; Roberts, Joan E.

2010-01-01

182

PIGMENTS OF THE RETINA  

PubMed Central

1. Visual purple from the sea robin, sea bass, and scup is almost identical spectroscopically with that from frogs. The interrelations of this pigment with vitamin A and retinene are also the same as in the frog. 2. In strong acids or at pH > 11, the visual yellow of sea robin retinas is converted irreversibly into a pH indicator, yellow in acid and almost colorless in alkaline solution. Unlike neutral visual yellow, the indicator is not removed to form either vitamin A or visual purple. In the ammoniacal retina the reversion of visual yellow itself to purple is accelerated. 3. The combined pigment epithelium and choroid layer in these fishes contain vitamin A, flavine, and an unidentified xanthophyll. PMID:19872983

Wald, George

1936-01-01

183

Pigments of cotton flowers  

Microsoft Academic Search

Summary  The flower petals of the Uppam cotton plant (G. herbaceum) contain as their main components gossypitrin and quercetin. An appreciable quantity of a new glycosidic pigment and a small\\u000a quantity of gossypetin were also isolated. Uppam petals, therefore, differ in their composition from those ofG. herbaceum examined by Perkin who probably obtained his supply of the petals from the North

K. Neelakantam; T. R. Seshadri; R. H. Ramachandra Rao

1935-01-01

184

[Pathogenetic concepts for pigment epithelial detachment in exudative AMD].  

PubMed

Retinal pigment epithelial detachment (PED) as a specific manifestation in exudative age-related macular degeneration (AMD) may lead to a substantial decrease of central vision. An understanding of important events during the development of PED is necessary for a successful therapeutic intervention. At present the leading pathogenetic theory is that of reduced hydraulic conductivity of Bruch's membrane. The mechanisms underlying this process are caused by increased deposition of lipids, enhanced collagen cross-linking and alteration in the ratio of tissue-dissolving enzymes and their inhibitors. The association of newly formed vessels and an unaltered RPE pump activity can lead to the clinical picture of serous PED during exudative AMD. PMID:21153575

Wasmuth, S

2010-12-01

185

Surgical outcomes of macular buckling techniques for macular retinoschisis in highly myopic eyes  

PubMed Central

Purpose To report the anatomic and visual results following macular buckling for patients with macular retinoschisis related to high myopia. Methods Thirty-nine highly myopic eyes (mean refractive error ?16.7 D; range, ?9 to ?24 D) of 36 patients (mean age 59 years; range, 35–79 years) presenting with macular retinoschisis associated with a posterior staphyloma, who underwent combined vitrectomy and macular buckling were evaluated. Main outcome measures included best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) findings. Three cases were excluded due to short follow-up (less than 3 months). The mean follow-up was 16 months. Results The mean BCVA increased from 0.76 to 0.43 LogMAR (p = 0.001). Visual acuity improved in 30 eyes (83.3%), remained stable in three eyes (8.3%) and decreased in three eyes (8.3%). OCT showed resolution of foveoschisis with foveal reattachment in all eyes. None of the evaluated patients developed a macular hole during follow-up. Conclusion Macular buckling associated with vitrectomy results in good anatomic and visual outcomes in patients with myopic foveoschisis. PMID:24409086

Mateo, Carlos; Gomez-Resa, Maria V.; Bures-Jelstrup, Anniken; Alkabes, Micol

2013-01-01

186

Evaluation of posturing in macular hole surgery  

Microsoft Academic Search

Aim To objectively evaluate the postoperative face down posturing in macular hole surgery.Materials and Methods An electronic device called ‘Maculog’ was developed consisting of three basic components, a mercury switch triggered by the angle of tilt placed inside an earpiece, a data-recording device connected to the earpiece with cables and a windows based software program, specially written to analyse the

D Verma; M W Jalabi; W G Watts; G Naylor

2002-01-01

187

Current status in diabetic macular edema treatments  

PubMed Central

Diabetes is a serious chronic condition, which increase the risk of cardiovascular diseases, kidney failure and nerve damage leading to amputation. Furthermore the ocular complications include diabetic macular edema, is the leading cause of blindness among adults in the industrialized countries. Today, blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy. The treatment should include an optimized control of glycemia, arterial tension, lipids and renal status. The photocoagulation laser is currently restricted to focal macular edema in some countries, but due the high cost of intravitreal drugs, the use of laser treatment for focal and diffuse diabetic macular edema (DME), can be valid as gold standard in many countries. The intravitreal anti vascular endothelial growth factor drugs (ranibizumab and bevacizumab), are indicated in the treatment of all types of DME, but the correct protocol for administration should be defined for the different Retina Scientific Societies. The corticosteroids for diffuse DME, has a place in pseudophakic patients, but its complications restricted the use of these drugs for some patients. Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients. PMID:24147200

Romero-Aroca, Pedro

2013-01-01

188

Depression in Age-Related Macular Degeneration  

ERIC Educational Resources Information Center

Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

Casten, Robin; Rovner, Barry

2008-01-01

189

Driving and Age-Related Macular Degeneration  

PubMed Central

This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research. PMID:20046818

Owsley, Cynthia; McGwin, Gerald

2009-01-01

190

Genetic susceptibility to age related macular degeneration  

Microsoft Academic Search

Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and a major cause of blindness in the developed world. The disease can take two forms, geographic atrophy and choroidal neovascularisation. The pathogenesis of AMD is poorly understood. There are undoubtedly environmental and other risk factors involved and the adverse effect of smoking is well

John R W Yates; Anthony T Moore

2000-01-01

191

Genetics of Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Age-related Macular Degeneration (AMD) is a multifactorial disease involving genetic and environmental influences. Complement\\u000a Factor H (CFH) and HTRA1\\/LOC387715 are the two main loci associated with AMD. A genetic understanding of AMD may allow for\\u000a early diagnosis and treatment.

Daniel T. Kasuga; Yuhong Chen; Kang Zhang

192

Management of traumatic macular holes: case report.  

PubMed

Traumatic macular hole is a disease whose pathogenesis is not fully understood and the best treatment guideline is controversial. We report 2 cases of traumatic macular hole with different treatment approaches. In the first case, a 9-year-old boy presented with a traumatic macular hole secondary to blunt ocular trauma with a stone, and initial vision of 20/300. He underwent surgical repair and his final vision was 20/70 with hole closure after a 1 year follow-up. In the second case, a 20-year-old woman suffered a penetrating bullet wound on the left side of her forehead. The injury caused optic nerve head avulsion in the left eye with loss of light perception. The right eye had a traumatic macular hole and signs suggestive of sclopetaria chorioretinitis, with 20/60 vision. This case was initially observed and vision improved to 20/30 with reduction of the hole diameter. Vision and hole diameter remained stable after 8 months. PMID:18797673

Brasil, Oswaldo Ferreira Moura; Brasil, Oswaldo Moura

2008-01-01

193

The Intravitreal Autologous Platelet Concentrate Injection as an Adjunct of Vitrectomy for the Treatment of Refractory Macular Holes  

ClinicalTrials.gov

Macular Hole With High Myopia (Spherical Equivalent ? -6.0 Diopters) or,; Large Size Macular Hole (Diameter > 600 Microns) or; Recurred or Failed Macular Hole From Previous Surgery; or Chronic Macular Hole (Symptom Duration > 6 Months)

2014-03-06

194

Novel Rodent Models for Macular Research  

PubMed Central

Background Many disabling human retinal disorders involve the central retina, particularly the macula. However, the commonly used rodent models in research, mouse and rat, do not possess a macula. The purpose of this study was to identify small laboratory rodents with a significant central region as potential new models for macular research. Methodology/Principal Findings Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli, laboratory rodents less commonly used in retinal research, were subjected to confocal scanning laser ophthalmoscopy (cSLO), fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT) using standard equipment (Heidelberg Engineering HRA1 and Spectralis™) adapted to small rodent eyes. The existence of a visual streak-like pattern was assessed on the basis of vascular topography, retinal thickness, and the topography of retinal ganglion cells and cone photoreceptors. All three species examined showed evidence of a significant horizontal streak-like specialization. cSLO angiography and retinal wholemounts revealed that superficial retinal blood vessels typically ramify and narrow into a sparse capillary net at the border of the respective area located dorsal to the optic nerve. Similar to the macular region, there was an absence of larger blood vessels in the streak region. Furthermore, the thickness of the photoreceptor layer and the population density of neurons in the ganglion cell layer were markedly increased in the visual streak region. Conclusions/Significance The retinal specializations of Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli resemble features of the primate macula. Hence, the rodents reported here may serve to study aspects of macular development and diseases like age-related macular degeneration and diabetic macular edema, and the preclinical assessment of therapeutic strategies. PMID:20976212

Huber, Gesine; Heynen, Severin; Imsand, Coni; vom Hagen, Franziska; Muehlfriedel, Regine; Tanimoto, Naoyuki; Feng, Yuxi; Hammes, Hans-Peter; Grimm, Christian; Peichl, Leo; Seeliger, Mathias W.; Beck, Susanne C.

2010-01-01

195

Pigment Dispersion Syndrome - Update 2003  

Microsoft Academic Search

\\u000a Pigment dispersion syndrome (PDS) is a unique and fascinating entity. It is far more prevalent, actually by an order of magnitude,\\u000a than previously suspected, comprising 2.45% of the screened Caucasian population in one study [76]. PDS and pigmentary glaucoma (PG) are characterized by disruption of the iris pigment epithelium (IPE) and deposition of\\u000a the dispersed pigment granules throughout the anterior

Robert Ritch

196

The response of human retinal pigmented epithelial cells in vitro to changes in nitric oxide concentration stimulated by low levels of red light  

NASA Astrophysics Data System (ADS)

The goal of this project is to explore the role of nitric oxide (NO) in regulating the response of hTERT-RPE to low-level exposures to red light. Exposure to low-level red light has been shown to positively affect wound healing, reduce pain, and encourage cell proliferation. The current explanation for this effect is described as an interaction between the photons and cytochrome c oxidase (Cco), which plays a role in regulation of intracellular NO levels in addition to being the mitochondrial protein complex where reduction of oxygen occurs in the process of oxidative phosphorylation. Exposure to 2.88 J/cm2 of 671-nm and 637-nm light shows a two-fold increase in NO immediately after exposure, and a 56% increase in ATP measured at ~5 h post exposure. Levels of NF-?B mRNA and protein were measured at six and 24 h, respectively, and found to increase six fold, correlating with increases in NO levels. Light-stimulated increased levels of NO also correlated with an 11-fold increase in Bcl-2 and a 70% decrease in Bax mRNA levels, relative to controls. NF-?B promotes cell growth and Bcl-2 is an apoptosis suppressor protein. Bax is a positive apoptotic effector protein. These results support the hypothesis that light-induced changes in the intracellular levels of NO play a role in the beneficial effects of low-level light photobiomodulation

Lavey, Brent J.; Estlack, Larry E.; Schuster, Kurt J.; Rockwell, Benjamin A.; Wigle, Jeffrey C.

2013-03-01

197

Facts about Age-Related Macular Degeneration  

MedlinePLUS

... In addition to the pigmented cells in the iris (the colored part of the eye), there are pigmented cells beneath the retina. As ... Know (NIH Publication No. 03-2294). The National Eye Institute ( NEI ) ... vision research that leads to sight-saving treatments and plays a key role in ...

198

Raman Spectroscopy of Microbial Pigments  

PubMed Central

Raman spectroscopy is a rapid nondestructive technique providing spectroscopic and structural information on both organic and inorganic molecular compounds. Extensive applications for the method in the characterization of pigments have been found. Due to the high sensitivity of Raman spectroscopy for the detection of chlorophylls, carotenoids, scytonemin, and a range of other pigments found in the microbial world, it is an excellent technique to monitor the presence of such pigments, both in pure cultures and in environmental samples. Miniaturized portable handheld instruments are available; these instruments can be used to detect pigments in microbiological samples of different types and origins under field conditions. PMID:24682303

Edwards, Howell G. M.; Oren, Aharon

2014-01-01

199

Ocular pigmentation in white and Siamese cats  

Microsoft Academic Search

Ocular pigmentation in white cats with blue and. yellow eyes and in Siamese cats was examined ophthalmoscopically and histologically. Yellow-eyed, white cats had. entirely normal ocular pigmentation. Blue eyes of white cats had. normal pigmentation of the iridial and. retinal pigment epithelia but no stromal pigmentation of the iris or choroid. This deficit is apparently due to the absence of

L. N. Thibos; W. R. Levick; R. Morstyn

1980-01-01

200

Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors.  

PubMed

The visual pigments of most invertebrate photoreceptors have two thermostable photo-interconvertible states, the ground state rhodopsin and photo-activated metarhodopsin, which triggers the phototransduction cascade until it binds arrestin. The ratio of the two states in photoequilibrium is determined by their absorbance spectra and the effective spectral distribution of illumination. Calculations indicate that metarhodopsin levels in fly photoreceptors are maintained below ~35% in normal diurnal environments, due to the combination of a blue-green rhodopsin, an orange-absorbing metarhodopsin and red transparent screening pigments. Slow metarhodopsin degradation and rhodopsin regeneration processes further subserve visual pigment maintenance. In most insect eyes, where the majority of photoreceptors have green-absorbing rhodopsins and blue-absorbing metarhodopsins, natural illuminants are predicted to create metarhodopsin levels greater than 60% at high intensities. However, fast metarhodopsin decay and rhodopsin regeneration also play an important role in controlling metarhodopsin in green receptors, resulting in a high rhodopsin content at low light intensities and a reduced overall visual pigment content in bright light. A simple model for the visual pigment-arrestin cycle is used to illustrate the dependence of the visual pigment population states on light intensity, arrestin levels and pigment turnover. PMID:21046112

Stavenga, Doekele G; Hardie, Roger C

2011-03-01

201

Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.  

PubMed

Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy. PMID:22683799

Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

2012-09-01

202

Outcomes of 23-gauge pars plana vitrectomy and internal limiting membrane peeling with brilliant blue in macular hole  

PubMed Central

Purpose: The evaluation of anatomic and visual outcomes in macular hole cases treated with internal limiting membrane (ILM) peeling, brilliant blue (BB), and 23-gauge pars plana vitrectomy (PPV). Materials and methods: Fifty eyes of 48 patients who presented between July 2007 and December 2009 with the diagnosis of stage 2, 3, or 4 macular holes according to Gass Classification who had undergone PPV and ILM peeling were included in this study. Pre- and postoperative macular examinations were assessed with spectral-domain optical coherence tomography. 23 G sutureless PPV and ILM peeling with BB was performed on all patients. Results: The mean age of patients was 63.34 ± 9.6 years. Stage 2 macular hole was determined in 17 eyes (34%), stage 3 in 24 eyes (48%), and stage 4 in 9 eyes (18%). The mean follow-up time was 13.6 ± 1.09 months. Anatomic closure was detected in 46/50 eyes (92%), whereas, in four cases, macular hole persisted and a second operation was not required due to subretinal fluid drainage. At follow-up after 2 months, persistant macular hole was detected in one case and it was closed with reoperation. At 12 months, an increase in visual acuity in 41 eyes was observed, while it remained at the same level in six eyes. In three eyes visual acuity decreased. There was a postoperative statistically significant increase in visual acuity in stage 2 and 3 cases (P < 0.05), however, no increase in visual acuity in stage 4 cases was observed. Conclusion: PPV and ILM peeling in stage 2, 3, and 4 macular hole cases provide successful anatomic outcomes, however, in delayed cases, due to photoreceptor loss, it has no effect on functional recovery. BB, used for clarity of ILM, may be beneficial due to its low retinal toxicity. PMID:21887101

Sanisoglu, Huseyin; Sevim, Mehmet Sahin; Aktas, Betul; Sevim, Semra; Nohutcu, Ahmet

2011-01-01

203

Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration  

PubMed Central

Activation of the alternative pathway of the complement system has been implicated in the pathogenesis of age-related macular degeneration. Membrane attack complex (MAC) has been identified mainly on the Bruch’s membrane and drusen underlying the retinal pigment epithelium (RPE). Membrane cofactor protein (CD46) preferentially regulates the alternative pathway of complement. The aim of this study was to evaluate the potential of increasing CD46 expression on RPE cells using an adenovirus as a gene therapy approach to reduce alternative pathway-mediated damage to RPE cells. We generated a recombinant adenovirus vector expressing human CD46 (hCD46) and delivered the vector to murine hepatocytes and RPE cells in vitro. After incubation in human serum in conditions in which the classical pathway of complement was blocked, we measured alternative pathway-mediated damage of these cells by quantifying lysis and MAC formation. Adenovirus expressing hCD46 was delivered to the subretinal space of adult mice, and 1 week later, ocular flat mounts were challenged with human serum and the levels of complement-mediated damage was quantified. Adenovirus-mediated delivery of hCD46 localizes to the basal and lateral surfaces of RPE cells where it offers protection from alternative pathway-mediated damage, but not classical, allowing the classical pathway to function unhindered. PMID:21307887

Sweigard, JH; Cashman, SM; Kumar-Singh, R

2014-01-01

204

Clinical characterization and genetic mapping of North Carolina macular dystrophy  

Microsoft Academic Search

North Carolina macular dystrophy (NCMD) is an autosomal dominant macular disease, was mapped to 6q14-q16.2, the disease-causing gene has yet not been identified. It shares phenotypic similarity with age-related macular degeneration including drusen and choroidal neovascularization. We collected six families with NCMD including 75 members, and conducted clinical characterization and genetic mapping for these families. Forty-five patients were diagnosed as

Zhenglin Yang; Zongzhong Tong; Louis J. Chorich; Erik Pearson; Xian Yang; Anthony Moore; David M. Hunt; Kang Zhang

2008-01-01

205

Spectral-Domain Optical Coherence Tomography Characteristics of Intermediate Age-Related Macular Degeneration  

PubMed Central

Purpose Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading. Design Prospective cross-sectional study. Participants We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD. Methods Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ?1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility. Main Outcome Measures We assessed SD-OCT characteristics at baseline. Results In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy. Conclusions Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression. PMID:22968145

Leuschen, Jessica N.; Schuman, Stefanie G.; Winter, Katrina P.; McCall, Michelle N.; Wong, Wai T.; Chew, Emily Y.; Hwang, Thomas; Srivastava, Sunil; Sarin, Neeru; Clemons, Traci; Harrington, Molly; Toth, Cynthia A.

2012-01-01

206

Imaging Retinal Pigment Epithelial Proliferation Secondary to PASCAL Photocoagulation In Vivo by Polarization-sensitive Optical Coherence Tomography  

PubMed Central

Purpose To image the retinal pigment epithelium (RPE) after macular laser and to monitor healing responses over time in vivo in patients with diabetic maculopathy using polarization-sensitive optical coherence tomography (OCT). Design Prospective, nonrandomized clinical trial. Methods In this single-center trial (Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria), 13 patients (13 eyes) underwent grid photocoagulation for diabetic maculopathy. Retinal healing processes were continuously followed over the course of 3 months. A polarization-sensitive OCT prototype was used, allowing detection and measurement of the RPE changes based on their specific polarization-scrambling qualities. Results After 1 day, the intraretinal photocoagulation lesions were sharply demarcated, whereas RPE changes were rather subtle. At 1 week, all lesions exhibited traction of the inner retinal layers toward the RPE and loss of photoreceptor cells. In tissue-sensitive polarization-sensitive OCT imaging, polarization-scrambling columns were found at the level of the RPE. During follow-up, different healing responses were seen in the polarization-scrambling RPE layer, ranging from hyperproliferation to focal atrophy. Conclusion Because of the properties of the polarization state of backscattered light, polarization-sensitive OCT revealed specific morphologic changes in the RPE and outer retinal layers secondary to retinal laser treatment undetectable with intensity-based spectral-domain OCT. The increase in polarization-scrambling tissue over the course of 3 months indicates a more intense healing reaction and proliferation of RPE cells than previously characterized in rodent studies. PMID:23498853

Lammer, Jan; Bolz, Matthias; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Mylonas, Georgios; Hitzenberger, Christoph K.; Schmidt-Erfurth, Ursula

2013-01-01

207

Development of a surface to increase retinal pigment epithelial cell (ARPE-19) proliferation under reduced serum conditions.  

PubMed

Age related macular degeneration of the eye is brought about by damage to the retinal pigment epithelium (RPE) and is a major cause of adult blindness. One potential treatment method is transplantation of RPE cells grown in vitro. Maintaining RPE cell viability and physiological function in vitro is a challenge, and this must also be achieved using materials that can be subsequently used to deliver an intact cell sheet into the eye. In this paper, plasma polymerisation has been used to develop a chemically modified surface for maintaining RPE cells in vitro. Multiwell plates modified with a plasma copolymer of allylamine and octadiene maintained RPE cell growth at a level similar to that of TCPS. However, the addition of bound glycosaminoglycans (GAGs) to the plasma polymerised surface significantly enhanced RPE proliferation. Simply adding GAG to the culture media had no positive effect. It is shown that a combination of plasma polymer and GAG is a promising method for developing suitable surfaces for cell growth and delivery, that can be applied to any substrate material. PMID:24493476

Zuber, Agnieszka A; Robinson, David E; Short, Robert D; Steele, David A; Whittle, Jason D

2014-05-01

208

Intravitreal bevacizumab for macular edema from idiopathic juxtafoveal retinal telangiectasis.  

PubMed

To assess the potential visual benefit of intravitreal bevacizumab in a patient with idiopathic juxtafoveal retinal telangiectasis refractory to focal laser treatment, an intravitreal injection of bevacizumab (1.25 mg) was given. Within 1 week, visual acuity improved from 20/50 to 20/25 and optical coherence tomography demonstrated complete resolution of macular edema. There was no adverse effect. The macular edema recurred after 3 months, requiring a repeat injection of bevacizumab with subsequent resolution of macular edema. An intravitreal injection of bevacizumab may provide potential short-term visual benefit in patients with macular edema from idiopathic juxtafoveal retinal telangiectasis. PMID:17396701

Moon, Suk J; Berger, Adam S; Tolentino, Michael J; Misch, David M

2007-01-01

209

Quantitative spatiotemporal image analysis of fluorescein angiography in age-related macular degeneration  

NASA Astrophysics Data System (ADS)

Interpretation and analysis of retinal angiographic studies has been largely qualitative. Quantitative analysis of pathologic fundus features will facilitate interpretation and potentiate clinical studies where precise image metrology is vital. Fluorescein angiography studies of patients with age- related macular degeneration were digitized. Sequential temporal images were spatially-registered with polynomial warping algorithms, allowing for the construction of a three- dimensional (two spatial and one temporal) angiogram vector. Temporal profiles through spatially-registered, temporally- sequential pixels were computed. Characteristic temporal profiles for fundus background, retinal vasculature, retinal pigment epithelial atrophy, and choroidal neovascular (CNV) membranes were observed, allowing for pixel assignment and fundus feature quantitation. Segmentation and quantitation of fundus features including geographic atrophy and CNV is facilitated by spatio-temporal image analysis.

Berger, Jeffrey W.

1998-06-01

210

Defective Lipid Transport and Biosynthesis in Recessive and Dominant Stargardt Macular Degeneration  

PubMed Central

Stargardt disease is a common inherited macular degeneration characterized by a significant loss in central vision in the first or second decade of life, bilateral atrophic changes in the central retina associated with degeneration of photoreceptors and underlying retinal pigment epithelial cells, and the presence of yellow flecks extending from the macula. Autosomal recessive Stargardt disease, the most common macular dystrophy, is caused by mutations in the gene encoding ABCA4, a photoreceptor ATP binding cassette (ABC) transporter. Biochemical studies together with analysis of abca4 knockout mice and Stargardt patients have implicated ABCA4 as a lipid transporter that facilitates the removal of potentially toxic retinal compounds from photoreceptors following photoexcitation. An autosomal dominant form of Stargardt disease also known as Stargardt-like dystrophy is caused by mutations in a gene encoding ELOVL4, an enzyme that catalyzes the elongation of very long chain fatty acids in photoreceptors and other tissues. This review focuses on the molecular characterization of ABCA4 and ELOVL4 and their role in photoreceptor cell biology and the pathogenesis of Stargardt disease. PMID:20633576

Molday, Robert S.; Zhang, Kang

2010-01-01

211

Quantitative Subanalysis of Optical Coherence Tomography after treatment with Ranibizumab for Neovascular Age-Related Macular Degeneration  

PubMed Central

Purpose To investigate the effects of ranibizumab on retinal morphology in patients with neovascular age-related macular degeneration (AMD) using optical coherence tomography (OCT) quantitative subanalysis. Methods Data from 95 patients receiving intravitreal ranibizumab for neovascular AMD were collected. StratusOCT images were analyzed using custom software entitled “OCTOR” which allows precise positioning of pre-specified boundaries on every B-scan. Changes in thickness/volume of the retina, subretinal fluid (SRF), subretinal tissue (SRT), and pigment epithelial detachments (PEDs) at week 1, and at months 1, 3, 6 and 9 post-treatment were calculated. Results Total retinal volume reached its nadir at month 1, with an average reduction of 0.43 mm3 (P<0.001). By month 9, this initial change had been reduced to a mean reduction of 0.32 mm3 (P=0.0011). Total SRF volume reached its lowest level by month 1, with an average reduction of 0.24 mm3 (P<0.001). This reduction lessened subsequently, to 0.18 mm3 by month 9. There was an average 0.3 mm3 decrease in total PED volume by month 1 (P<0.001), and this later declined further, to 0.45 mm3 by month 9 (P=0.0014). Total SRT volume was reduced by an average of 0.07 mm3 at month 1 (P=0.0159) and subsequently remained constant. Conclusions Although neurosensory retinal edema and SRF, showed an early reduction to nadir following initiation of ranibizumab therapy, the effect on the retina was attenuated over time, suggesting a possible tachyphylaxis. PED volume showed a slower but progressive reduction. Manual quantitative OCT subanalysis may allow a more precise understanding of anatomic outcomes and their correlation with visual acuity. PMID:18408176

Keane, Pearse A.; Liakopoulos, Sandra; Ongchin, Sharel C.; Heussen, Florian M.; Msutta, Sandeep; Chang, Karen T.; Walsh, Alexander C.

2008-01-01

212

A Non Membrane-Targeted Human Soluble CD59 Attenuates Choroidal Neovascularization in a Model of Age Related Macular Degeneration  

PubMed Central

Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD. PMID:21552568

Kumar-Singh, Rajendra

2011-01-01

213

New directions in phthalocyanine pigments  

NASA Technical Reports Server (NTRS)

Phthalocyanines have been used as a pigment in coatings and related applications for many years. These pigments are some of the most stable organic pigments known. The phthalo blue and green pigments have been known to be ultraviolet (UV) stable and thermally stable to over 400 C. These phthalocyanines are both a semiconductor and photoconductor, exhibiting catalytic activity and photostabilization capability of polymers. Many metal free and metallic phthalocyanine derivatives have been prepared. Development of the new classes of phthalocyanine pigment could be used as coating on NASA spacecraft material such as glass to decrease the optical degradation from UV light, the outside of the space station modules for UV protection, and coating on solar cells to increase lifetime and efficiency.

Trinh, Diep VO

1994-01-01

214

Porous Poly(?-Caprolactone) Scaffolds for Retinal Pigment Epithelium Transplantation  

PubMed Central

Purpose. Retinal pigment epithelium (RPE) transplantation is a promising strategy for the treatment of dry age-related macular degeneration (AMD). However, previous attempts at subretinal RPE cell transplantation have experienced limited success due to poor adhesion, organization, and function on aged or diseased Bruch's membrane. Instead, cell-based strategies may benefit from a synthetic scaffold that mimics the functions of healthy Bruch's membrane to promote the formation of a functional RPE monolayer while maintaining metabolite exchange between the vasculature and outer retina. Methods. This study evaluated the behavior of human RPE on nanopatterned porous poly(?-caprolactone) (PCL) film as a potential scaffold for therapeutic transplantation. Fetal human RPE (fhRPE) was cultured on porous PCL, nonporous PCL, or Costar porous polyester transwells for up to 8 weeks and assessed using light microscopy, fluorescent microscopy, transepithelial resistance, quantitative PCR, ELISAs, and phagocytosis assays. Results. fhRPE on porous PCL displayed improved markers of maturity and function compared with both porous polyester transwells and nonporous PCL, including pigmentation, increased cell density, superior barrier function, up-regulation of RPE-specific genes, and polarized growth factor secretion. Conclusions. This study indicates that porous PCL is an attractive scaffold for RPE transplantation. In addition to being biocompatible with the subretinal space, porous PCL also allows for trans-scaffold metabolite transport and significantly improves RPE cell behavior compared to nonporous PCL or porous polyester transwells. PMID:24550370

McHugh, Kevin J.; Tao, Sarah L.; Saint-Geniez, Magali

2014-01-01

215

[New aspects in age related macular degeneration].  

PubMed

Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina. PMID:22888685

Turlea, C

2012-01-01

216

Effect of Amaranthus Pigments on Quality Characteristics of Pork Sausages  

PubMed Central

The objective of this investigation was to evaluate the possibility of substituting Amaranthus pigments for nitrates in the of manufacture pork sausage. Five treatments of pork sausages (5% fat) with two levels of sodium nitrite (0 and 0.015%), or three levels (0.1%, 0.2% and 0.3%) of pigments extracted from red Amaranthus were produced. The addition of Amaranthus pigments resulted in the significant increase of a* values, sensory color, flavor and overall acceptance scores, but the significant reduction of b* values, TBA values and VBN values (p<0.05). Based mainly on the results of overall acceptance during 29 d storage, it could be concluded that Amaranthus pigments showed a potential as nitrite alternative for pork sausage manufacture. PMID:25049507

Zhou, Cunliu; Zhang, Lin; Wang, Hui; Chen, Conggui

2012-01-01

217

Prevention of age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective\\u000a treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment\\u000a for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review\\u000a looks at current evidence on preventive

Ian Yat Hin Wong; Simon Chi Yan Koo; Clement Wai Nang Chan

2011-01-01

218

[Hemorrhagic macular choroidopathy in young subjects].  

PubMed

The haemorrhagic macular choroidopathy is a characteristic and rather frequent disease, which is seen in young subjects. We observed it in 23 patients, aged between 12 and 51 years. The disease resembles the presumed histoplasmin choroiditis, described in the American literature. In our cases, histoplasmosis can nevertheless be excluded and in the American cases it is not proven. In fact, the etiology is still unknown, but in 13 of our cases the origin may have been a disseminated choroiditis. PMID:1128878

Francois, J; DeLaey, J J; Dakir, M

1975-01-01

219

Effect of high-level oxygen exposure on the peroxidase activity and the neuromelanin-like pigment content of the nerve net in the earthworm, Lumbricus terrestris  

Microsoft Academic Search

Histochemical examination of 1-7m tissue sections from the dorsal nerve plexus of the earthworm, Lumbricus terrestris, reveals multiple brown intraneuronal granules. These granules contain material morphologically and histochemically consistent with neuromelanin. When viewed with transmission electron microscopy, these were seen as single membrane-enclosed biphasic granules with diameters of 370-730 nm. Exposure of L. terrestris to high-level environmental oxygen resulted in

William E. Fyffe; Joseph D. Kronz; Paul A. Edmonds; Thomas M. Donndelinger

1999-01-01

220

[Vitrectomy with autoserum for idiopathic macular hole].  

PubMed

Using autoserum, we operated on eyes with full thickness macular hole and achieved greater anatomic and visual success than with eyes that underwent vitrectomy alone. A total of 34 eyes were treated with vitrectomy and fluid-gas exchange: 14 eyes with autoserum instillation and 15 eyes without autoserum. Five eyes with macular holes persisting after initial vitrectomy underwent reoperation with autoserum. After vitrectomy and fluid-air exchange, 0.1 to 0.3 ml of autoserum was placed for about 7 minutes over the hole, and then 30% SF6 was instilled. After treatment, successful anatomic closure occurred in 53% of the eyes without autoserum, in 86% of those with autoserum, and in 80% of those which underwent reoperation with autoserum. Visual acuity improved 2 lines or more in 53% of the eyes without autoserum, in 79% of those with autoserum, and in 60% of those that underwent reoperation with autoserum. The results of the current preliminary study shows that treatment of full-thickness macular holes with autoserum seems to be more beneficial than vitrectomy alone. PMID:8712078

Mori, K; Yoneya, S; Abe, T

1996-06-01

221

Macular Bioaccelerometers on Earth and in Space  

NASA Technical Reports Server (NTRS)

Space flight offers the opportunity to study linear bioaccelerometers (vestibular maculas) in the virtual absence of a primary stimulus, gravitational acceleration. Macular research in space is particularly important to NASA because the bioaccelerometers are proving to be weighted neural networks in which information is distributed for parallel processing. Neural networks are plastic and highly adaptive to new environments. Combined morphological-physiological studies of maculas fixed in space and following flight should reveal macular adaptive responses to microgravity, and their time-course. Ground-based research, already begun, using computer-assisted, 3-dimensional reconstruction of macular terminal fields will lead to development of computer models of functioning maculas. This research should continue in conjunction with physiological studies, including work with multichannel electrodes. The results of such a combined effort could usher in a new era in understanding vestibular function on Earth and in space. They can also provide a rational basis for counter-measures to space motion sickness, which may prove troublesome as space voyager encounter new gravitational fields on planets, or must re-adapt to 1 g upon return to earth.

Ross, M. D.; Cutler, L.; Meyer, G.; Vazin, P.; Lam, T.

1991-01-01

222

Natural pigments and sacred art  

NASA Astrophysics Data System (ADS)

Since the dawn of mankind, cavemen has expressed himself through art. The earliest known cave paintings date to some 32,000 years ago and used 4 colours derived from the earth. These pigments were iron oxides and known as ochres, blacks and whites. All pigments known by the Egyptians, the Greeks, the Romans and Renaissance man were natural and it was not until the 18th century that synthetic pigments were made and widely used. Until that time all art, be it sacred or secular used only natural pigments, of which the preparation of many have been lost or rarely used because of their tedious preparation. As a geologist, a mineralogist and an artist specializing in iconography, I have been able to rediscover 89 natural pigments extracted from minerals. I use these pigments to paint my icons in the traditional Byzantine manner and also to restore old icons, bringing back their glamour and conserving them for years to come. The use of the natural pigments in its proper way also helps to preserve the traditional skills of the iconographer. In the ancient past, pigments were extremely precious. Many took an exceedingly long journey to reach the artists, and came from remote countries. Research into these pigments is the work of history, geography and anthropology. It is an interesting journey in itself to discover that the blue aquamarines came from Afghanistan, the reds from Spain, the greens Africa, and so on. In this contribution I will be describing the origins, preparation and use of some natural pigments, together with their history and provenance. Additionally, I will show how the natural pigments are used in the creation of an icon. Being a geologist iconographer, for me, is a sacrement that transforms that which is earthly, material and natural into a thing of beauty that is sacred. As bread and wine in the Eucharist, water during baptism and oil in Holy Union transmit sanctification to the beholder, natural pigments do the same when one considers an icon. The iconographer uses earthly creations to create divine images: "Thine own of Thine own we offer unto Thee." (Byzantine Liturgy). Thus, by combining geology with art and religion, I can render homage to God through His creation by using minerals of the Planet Earth, as natural pigments in painting His image.

Kelekian, Lena, ,, Lady

2010-05-01

223

Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study  

Microsoft Academic Search

AimsTo evaluate the outcome after two types of retinal pigment epithelium (RPE) transplantation techniques.MethodsFourteen consecutive patients with advanced exudative age-related macular degeneration (AMD) were randomly assigned to RPE-choroid sheet transplantation (group 1) or RPE cell-suspension transplantation (group 2). Outcome measures included best corrected distance and near visual acuity (BCVA), complication and recurrence rates, autofluorescence (AF), angiography, and time-domain and spectral-domain

Christiane I Falkner-Radler; Ilse Krebs; Carl Glittenberg; Boris Považay; Wolfgang Drexler; Alexandra Graf; Susanne Binder

2010-01-01

224

Expression of reverse cholesterol transport proteins ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI) in the retina and retinal pigment epithelium  

Microsoft Academic Search

Aims:Excessive lipid accumulation in Bruch’s membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move lipid into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI).Methods:ABCA1 expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) and

K G Duncan; K Hosseini; K R Bailey; H Yang; R J Lowe; M T Matthes; J P Kane; M M LaVail; D M Schwartz; J L Duncan

2009-01-01

225

Temsirolimus Inhibits Proliferation and Migration in Retinal Pigment Epithelial and Endothelial Cells via mTOR Inhibition and Decreases VEGF and PDGF Expression  

PubMed Central

Due to their high prevalence, retinal vascular diseases including age related macular degeneration (AMD), retinal vein occlusions (RVO), diabetic retinopathy (DR) and diabetic macular edema have been major therapeutic targets over the last years. The pathogenesis of these diseases is complex and yet not fully understood. However, increased proliferation, migration and angiogenesis are characteristic cellular features in almost every retinal vascular disease. The introduction of vascular endothelial growth factor (VEGF) binding intravitreal treatment strategies has led to great advances in the therapy of these diseases. While the predominant part of affected patients benefits from the specific binding of VEGF by administering an anti-VEGF antibody into the vitreous cavity, a small number of non-responders exist and alternative or additional therapeutic strategies should therefore be evaluated. The mammalian target of rapamycin (mTOR) is a central signaling pathway that eventually triggers up-regulation of cellular proliferation, migration and survival and has been identified to play a key role in angiogenesis. In the present study we were able to show that both retinal pigment epithelial (RPE) cells as wells as human umbilical vein endothelial cells (HUVEC) are inhibited in proliferating and migrating after treatment with temsirolimus in non-toxic concentrations. Previous studies suggest that the production of VEGF, platelet derived growth factor (PDGF) and other important cytokines is not only triggered by hypoxia but also by mTOR itself. Our results indicate that temsirolimus decreases VEGF and PDGF expression on RNA and protein levels significantly. We therefore believe that the mTOR inhibitor temsirolimus might be a promising drug in the future and it seems worthwhile to evaluate complementary therapeutic effects with anti-VEGF drugs for patients not profiting from mono anti-VEGF therapy alone. PMID:24586308

Siedlecki, Jakob; Haritoglou, Christos; Kampik, Anselm; Kernt, Marcus

2014-01-01

226

Inorganic yellow-red pigments without toxic metals  

NASA Astrophysics Data System (ADS)

Inorganic pigments have been utilized by mankind since ancient times, and are still widely used to colour materials exposed to elevated temperatures during processing or application. Indeed, in the case of glasses, glazes and ceramics, there is no alternative to inorganic pigments for colouring. However, most inorganic pigments contain heavy metals or transition metals that can adversely effect the environment and human health if critical levels are exceeded. Cadmium-based pigments in particular are a cause of concern: although the pigments are not toxic due to their very low solubility in water and dilute mineral acids, cadmium itself is toxic and can enter the environment in a bioavailable form through waste-disposal sites and incineration plants. This has led to regulations, based on the precautionary principle, that strongly restrict the use of cadmium pigments. And even though recent assessments have concluded that the risk to humans or the environment might be not as significant as originally feared, a strong demand for inherently safer substitutes remains. Here we demonstrate that solid solutions of the perovskites CaTaO 2N and LaTaON2 constitute promising candidates for such substitutes: their brilliance, tinting strength, opacity, dispersability, light-fastness and heat stability rival that of the cadmium pigments, while their colour can be tuned through the desired range, from yellow through orange to deep red, by simple composition adjustments. Because all the constituent elements are harmless, this perovskite-based inorganic pigment system seems a promising replacement that could eliminate one of the sources for cadmium emissions to the environment and some of the remaining concerns about pigment safety.

Jansen, M.; Letschert, H. P.

2000-04-01

227

Automatic classification of diabetic macular edema in digital fundus images  

Microsoft Academic Search

Diabetic macular edema is a common complication of diabetic retinopathy due to the presence of exudates in proximity with the fovea. In this paper, an automated method to classify diabetic macular edema is presented. The fovea is localized and the regions of macula are marked based on the Early Treatment Diabetic Retinopathy Studies (ETDRS) grading scale. Extraction method using marker-controlled

S. T. Lim; W. M. D. W. Zaki; A. Hussain; S. L. Lim; S. Kusalavan

2011-01-01

228

The triple flash electroretinogram and its significance in macular diseases  

Microsoft Academic Search

• Purpose: The purpose of this study was to evaluate recovery data for the b-wave of the electroretinogram (ERG) elicited using multiple flash stimulation with increasing stimulus intervals in normal controls and in patients with macular diseases. The results will describe effects of age and macular disease and define indexes characterizing the recovery process. • Methods: Scotopic Ganzfeld flash ERGS

Karl Ulrich Bartz-Schmidt; Richard Brunner; Peter Esser; Christoph Liike; Peter Walter; Werner Sickel

1996-01-01

229

Age-Related Macular Degeneration: Etiology, Pathogenesis, and Therapeutic Strategies  

Microsoft Academic Search

Age-related macular degeneration is the principal cause of registered legal blindness among those aged over 65 in the United States, western Europe, Australia, and Japan. Despite intensive research, the precise etiology of molecular events that underlie age-related macular degeneration is poorly understood. However, investigations on parallel fronts are addressing this prevalent public health problem. Sophisticated biochemical and biophysical techniques have

Jayakrishna Ambati; Balamurali K Ambati; Sonia H Yoo; Sean Ianchulev; Anthony P Adamis

2003-01-01

230

Examination of macular vitreoretinal interface disorders with monochromatic photography.  

PubMed

Monochromatic light accentuates details of different retinal layers because of its variable absorption and reflectance by structures both within and above these layers. Monochromatic photography was used to examine macular vitreoretinal interface abnormalities in 19 patients. Short wavelength photographs (490 nm) provided the best detail of inner retinal abnormalities, including epiretinal membranes, vitreoretinal traction, and the internal surface of confluent macular edema (pseudocyst). Although 540-nm red-free photography provided acceptable photographs, it did not provide optimal detail of inner or deep retinal abnormalities. Longer wavelengths, 585 and 610 nm, best disclosed the extent of deep retinal abnormalities, including the extent of confluent macular edema (pseudocysts) and retinal detachment that surrounded macular holes. The addition of short- and long-wave-length photography to traditional red-free photography may provide better localization, understanding, and documentation of the three-dimensional relationships in macular vitreoretinal interface disorders. PMID:1543217

Ortiz, R G; Lopez, P F; Lambert, H M; Sternberg, P; Aaberg, T M

1992-03-15

231

Osmotic stress decreases aquaporin-4 expression in the human retinal pigment epithelial cell line, ARPE-19.  

PubMed

The regulation of water movement is of utmost importance for normal retinal function. Under physiological conditions, water is transported, dependent on the osmotic gradient, through the retinal pigment epithelial cell layer from the subretinal space to the choroid. The osmotic gradient has been found to be modified in eye diseases, thus leading to water accumulation in the subretinal space and the sensory retina, and subsequently contributing to the formation of macular oedema. Understanding the regulation of aquaporin expression is therefore crucial. In this study, we investigated the effects of hyperosmolarity on aquaporin-4 (AQP4) protein expression in the human retinal pigment epithelial cell line, ARPE?19. AQP4 expression was examined by PCR, western blot analysis and immunofluorescence. Ubiquitinylation was examined by immunoprecipitation. The results revealed that hyperosmotic stress rapidly decreased AQP4 expression in the ARPE-19 cells. The effect remained unmodified by lysosomal or mitogen-activated protein kinase inhibitors, but was reversed by proteasome inhibitors. However, no ubiquitinylation of AQP4 was detected. Our results suggest that hyperosmotic stress markedly reduces AQP4 expression possibly through a proteasome ubiquitinylation-independent pathway. This may represent an adaptation to hyperosmotic stress. The results presented in this study contribute to our understanding of the formation of macular oedema. PMID:24888368

Willermain, François; Janssens, Sarah; Arsenijevic, Tatjana; Piens, Isabelle; Bolaky, Nargis; Caspers, Laure; Perret, Jason; Delporte, Christine

2014-08-01

232

Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure  

PubMed Central

The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4?/? than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane. PMID:22570475

Boyer, Nicholas P.; Higbee, Daniel; Currin, Mark B.; Blakeley, Lorie R.; Chen, Chunhe; Ablonczy, Zsolt; Crouch, Rosalie K.; Koutalos, Yiannis

2012-01-01

233

Pigments of Volucrispora Aurantiaca Haskins.  

National Technical Information Service (NTIS)

In attempts to obtain a fully defined medium for studies on the biosynthesis of the unusual meta-hydroxylated terphenylquinone volucrisporin, by the Hyphomycete Volucrispora aurantiaca Haskins, it was observed that the type of pigment produced by the fung...

L. C. Vining, L. R. Nesbitt, R. H. Haskins

1965-01-01

234

Novel Compstatin Family Peptides Inhibit Complement Activation by Drusen-Like Deposits in Human Retinal Pigmented Epithelial Cell Cultures  

PubMed Central

We have used a novel human retinal pigmented epithelial (RPE) cell-based model that mimics drusen biogenesis and the pathobiology of age-related macular degeneration to evaluate the efficacy of newly designed peptide inhibitors of the complement system. The peptides belong to the compstatin family and, compared to existing compstatin analogs, have been optimized to promote binding to their target, complement protein C3, and to enhance solubility by improving their polarity/hydrophobicity ratios. Based on analysis of molecular dynamics simulation data of peptide-C3 complexes, novel binding features were designed by introducing intermolecular salt bridge-forming arginines at the N-terminus and at position -1 of N-terminal dipeptide extensions. Our study demonstrates that the RPE cell assay has discriminatory capability for measuring the efficacy and potency of inhibitory peptides in a macular disease environment. PMID:23954241

Gorham, Ronald D.; Forest, David L.; Tamamis, Phanourios; de Victoria, Aliana López; Kraszni, Márta; Kieslich, Chris A.; Banna, Christopher D.; Bellows-Peterson, Meghan L.; Larive, Cynthia K.; Floudas, Christodoulos A.; Archontis, Georgios; Johnson, Lincoln V.; Morikis, Dimitrios

2013-01-01

235

Vitrectomy Combined with Intravitreal Triamcinolone Acetonide Injection and Macular Laser Photocoagulation for Nontractional Diabetic Macular Edema  

PubMed Central

Purpose To evaluate the efficacy of vitrectomy combined with intravitreal injection of triamcinolone acetonide (IVTA) and macular laser photocoagulation for the treatment of nontractional diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) therapy. Methods Twenty-eight eyes from 28 subjects who were diagnosed with nontractional DME refractory to three or more sequential anti-VEGF injections underwent sequential vitrectomy, IVTA, and macular laser photocoagulation. Changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) during the six months following vitrectomy were evaluated. Additionally, the CST and BCVA outcomes were compared with those of 26 eyes treated with the same triple therapy for nontractional DME refractory to conventional treatment, such as IVTA or macular laser photocoagulation, or both. Results The mean logarithm of the minimum angle of resolution BCVAs before and one, three, and six months after vitrectomy were 0.44 ± 0.15, 0.36 ± 0.18, 0.31 ± 0.14, and 0.34 ± 0.22, respectively. The mean CSTs were 433.3 ± 77.9, 329.9 ± 59.4, 307.2 ± 60.2, and 310.1 ± 80.1 microns, respectively. The values of both BCVA and CST at one, three, and six months were significantly improved from baseline (p < 0.05). The extent of CST reduction during the first month after triple therapy was greater in eyes refractory to conventional treatment than in eyes refractory to anti-VEGF (p = 0.012). Conclusions Vitrectomy combined with IVTA and macular laser photocoagulation had a beneficial effect on both anatomical and functional outcomes in eyes with nontractional DME refractory to anti-VEGF therapy. PMID:23730111

Kim, Jae Hui; Ha, Hyo Shin; Kim, Jae Ryung

2013-01-01

236

Inhibitors of intracellular signaling pathways that lead to stimulated epidermal pigmentation: perspective of anti-pigmenting agents.  

PubMed

Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and unstimulated level. Thus, owing to the difficulty of confining topical application to a specific hyperpigmented skin area, potent anti-pigmenting agents capable of attenuating the natural unstimulated pigmentation process have the risk of leading to hypopigmentation. Since intracellular signaling pathways within melanocytes do not function substantially in maintaining normal skin color and are activated only by environmental stimuli such as UV radiation, specifically down-regulating the activation of melanogenesis to the constitutive level would be an appropriate strategy to develop new potent anti-pigmenting agents with a low risk of hypopigmentation. In this article, we review the hyperpigmentation mechanisms and intracellular signaling pathways that lead to the stimulation of melanogenesis. We also discuss a screening and evaluation system to select candidates for new anti-melanogenic substances by focusing on inhibitors of endothelin-1 or stem cell factor-triggered intracellular signaling cascades. From this viewpoint, we show that extracts of the herbs Withania somnifera and Melia toosendan and the natural chemicals Withaferin A and Astaxanthin are new candidates for potent anti-pigmenting substances that avoid the risk of hypopigmentation. PMID:24823877

Imokawa, Genji; Ishida, Koichi

2014-01-01

237

Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents  

PubMed Central

Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and unstimulated level. Thus, owing to the difficulty of confining topical application to a specific hyperpigmented skin area, potent anti-pigmenting agents capable of attenuating the natural unstimulated pigmentation process have the risk of leading to hypopigmentation. Since intracellular signaling pathways within melanocytes do not function substantially in maintaining normal skin color and are activated only by environmental stimuli such as UV radiation, specifically down-regulating the activation of melanogenesis to the constitutive level would be an appropriate strategy to develop new potent anti-pigmenting agents with a low risk of hypopigmentation. In this article, we review the hyperpigmentation mechanisms and intracellular signaling pathways that lead to the stimulation of melanogenesis. We also discuss a screening and evaluation system to select candidates for new anti-melanogenic substances by focusing on inhibitors of endothelin-1 or stem cell factor-triggered intracellular signaling cascades. From this viewpoint, we show that extracts of the herbs Withania somnifera and Melia toosendan and the natural chemicals Withaferin A and Astaxanthin are new candidates for potent anti-pigmenting substances that avoid the risk of hypopigmentation. PMID:24823877

Imokawa, Genji; Ishida, Koichi

2014-01-01

238

Human skin pigmentation as an adaptation to UV radiation  

PubMed Central

Human skin pigmentation is the product of two clines produced by natural selection to adjust levels of constitutive pigmentation to levels of UV radiation (UVR). One cline was generated by high UVR near the equator and led to the evolution of dark, photoprotective, eumelanin-rich pigmentation. The other was produced by the requirement for UVB photons to sustain cutaneous photosynthesis of vitamin D3 in low-UVB environments, and resulted in the evolution of depigmented skin. As hominins dispersed outside of the tropics, they experienced different intensities and seasonal mixtures of UVA and UVB. Extreme UVA throughout the year and two equinoctial peaks of UVB prevail within the tropics. Under these conditions, the primary selective pressure was to protect folate by maintaining dark pigmentation. Photolysis of folate and its main serum form of 5-methylhydrofolate is caused by UVR and by reactive oxygen species generated by UVA. Competition for folate between the needs for cell division, DNA repair, and melanogenesis is severe under stressful, high-UVR conditions and is exacerbated by dietary insufficiency. Outside of tropical latitudes, UVB levels are generally low and peak only once during the year. The populations exhibiting maximally depigmented skin are those inhabiting environments with the lowest annual and summer peak levels of UVB. Development of facultative pigmentation (tanning) was important to populations settling between roughly 23° and 46° , where levels of UVB varied strongly according to season. Depigmented and tannable skin evolved numerous times in hominin evolution via independent genetic pathways under positive selection. PMID:20445093

Jablonski, Nina G.; Chaplin, George

2010-01-01

239

The potential role of amyloid ? in the pathogenesis of age-related macular degeneration  

PubMed Central

Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid ? (A?) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of A? on cultured human RPE cells as well as ocular findings in neprilysin gene–disrupted mice, which leads to an increased deposition A?. The results showed that A? treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from A?-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene–disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that A? accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of A? reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD. PMID:16167083

Yoshida, Takeshi; Ohno-Matsui, Kyoko; Ichinose, Shizuko; Sato, Tetsuji; Iwata, Nobuhisa; Saido, Takaomi C.; Hisatomi, Toshio; Mochizuki, Manabu; Morita, Ikuo

2005-01-01

240

Autoantibodies to retinal astrocytes associated with age-related macular degeneration.  

PubMed

Sera from 128 patients with age-related macular degeneration (AMD) were examined and profiles of a variety of serum constituents, including immunoglobulins, alpha and beta globulins and autoantibodies, were tabulated. A similar series of tests were carried out on 20 control sera. The results indicate a higher incidence of serum abnormalities, particularly involving alpha-2 globulin, in patients with disturbance of pigmentation of the retinal pigment epithelium (RPE). The sera were further tested for the presence of autoantibodies with specificity for retinal tissue, and five major staining patterns were observed. Many sera produced patterns of labelling on human retina identical to that observed using labelled monoclonal anti-glial fibrillary acid protein (GFAP) antibodies, which are an established marker of retinal astrocytes. Although anti-retinal autoantibodies have been reported in association with a number of ocular pathologies, the observation of anti-astrocyte autoantibodies is new. Astrocytes are involved in the maintenance of the blood-retinal barrier (BRB) and also appear to be the facultative antigen-presenting cells of neural tissue. The present results indicate that the formation of anti-astrocyte autoantibodies may be an early feature of the pathogenesis of AMD. PMID:2193850

Penfold, P L; Provis, J M; Furby, J H; Gatenby, P A; Billson, F A

1990-01-01

241

Macular hole in Beh?et's disease  

PubMed Central

Objective: To investigate the clinical features, prevalence, role of surgical intervention and the visual prognosis of macular holes (MH) in patients with Behcet's disease (BD). Materials and Methods: Retrospective study of patients with BD and MH from January 1998 to November 2008. Results: Out of 159 patients, 21 eyes of 17 patients were identified with MH. The mean age was 38.59 (range 23-61) years and the mean follow-up period was 5.1 years (range 13-164 months). The prevalence of MH was 7%. Visual acuity (VA) at the time of presentation ranged from 20/70 to hand-motion. Optical coherence tomography (OCT) findings revealed intraretinal cysts at the edge of the MH. The mean size of MH was 983.6 um; 52% had elevated edges, 43% had flat edges and only one eye (5%) was closed postoperatively. Fluorescein angiography (FA) was consistent with macular ischemia in 76% of the cases. Human leukocyte antigen (HLA) B51 association was found in 14 of the 15 patients investigated. Six patients (out of 17) underwent pars plana vitrectomy. The final VA on their last follow-up ranged from 20/70 to 2/200. Surgical intervention for MH did not result in any visual improvement as compared to non-operated eyes. One patient lost vision completely due to elevated intraocular pressure post vitrectomy and silicon oil tamponade. Conclusions: MH in patients with BD may lead to significant visual disability. Surgical intervention does not seem to have any potential beneficial effect on the VA, probably due to significant macular ischemia and sequelae from the ocular inflammation. PMID:21836340

Al-Dhibi, Hassan; Abouammoh, Marwan; Al-Harthi, Essam; Al-Gaeed, Abdulrahman; Larsson, Jorgen; Abboud, Emad; Chaudhry, Imtiaz

2011-01-01

242

Fumed metallic oxides and conventional pigments for glossy inkjet paper  

NASA Astrophysics Data System (ADS)

Product development activity in the area of inkjet printing papers has accelerated greatly to meet the rapidly growing market for inkjet papers. Advancements in inkjet printing technology have also placed new demands on the paper substrate due to faster printing rates, greater resolution through increased drop volumes, and colorants added to the ink. To meet these requirements, papermakers are turning to pigmented size press formulations or pigmented coating systems. For inkjet coating applications, both the internal porosity of the pigment particles as well as the packing porosity of the coating affect print quality and dry time. Pores between the pigment particles allow for rapid diffusion of ink fluids into the coating structure, while also providing capacity for ink fluid uptake. Past research has shown the presence of coating cracks to increase the microroughness of the papers, consequently reducing the gloss of the silica/polyvinyl alcohol based coating colors. Coating cracks were not observed, at the same level of magnification, in the scanning electron microscopy images of alumina/polyvinyl alcohol coated papers. Studies are therefore needed to understand the influence of coating cracking on the microroughening of silica/polyvinyl alcohol based coatings and consequences to coating and ink gloss. Since micro roughening is known to be linked to shrinkage of the coating layer, studies are needed to determine if composite pigments can be formulated, which would enable the coating solids of the formulations to be increased to minimize the shrinkage of coating layer during drying. Coating solids greater than 55% solids are needed to reduce the difference between application solids and the coating's immobilization solids point in order to reduce shrinkage. The aim of this research was to address the above mentioned needed studies. Studies were performed to understand the influence of particle packing on gloss and ink jet print quality. Composite pigment structures were built using well-characterized pigments to determine the influence of particle size and particle size distribution on coating application solids, coatings immobilization solids on coating gloss and print attributes. This research consists of five articles which have all been accepted for publication: (1) Influence of Pigment Particles on the Gloss and Printability of Inkjet Coated Papers, (2) Influence of Silica and Alumina Oxide Pigments on Coating Structure and Print Quality of Inkjet Papers, (3) Production of a Single Coated Glossy Inkjet Paper Using Conventional Coating and Calendering Methods, (4) Influence of Pigment Particle Size and Packing Volume on the Printability of Glossy Inkjet Paper Coatings-Part I, and (5) Influence of Pigment Selection on Printability of Glossy Inkjet Paper Coatings-Part II.

Lee, Hyunkook

243

Macular abnormalities in Italian patients with retinitis pigmentosa  

PubMed Central

Aim To investigate the prevalence of macular abnormalities in a large Caucasian cohort of patients affected by retinitis pigmentosa (RP). Methods A retrospective study was performed by reviewing the medical records and optical coherence tomography (OCT) scans in a cohort of 581 RP patients in order to assess the presence of macular abnormalities —that is, cystoid macular oedema (CMO), epiretinal membrane (ERM), vitreo-macular traction syndrome, and macular hole. Results Macular abnormalities were observed in 524 (45.1%) out of the 1161 examined eyes. The most frequent abnormality was CMO, observed in 237 eyes (20.4%) from 133 patients (22.9%), followed by ERM, assessed in 181 eyes (15.6%) from 115 patients (19.8%). Moreover, vitreo-retinal abnormalities were significantly (p<0.05) associated with older age, cataract surgery, or cataract. CMO appeared to be significantly (p<0.05) associated with female gender, autosomic dominant inheritance pattern, and cataract. Conclusions Macular abnormalities are more frequent in RP compared to the general population. For that reason, screening RP patients with OCT is highly recommended to follow-up the patients, evaluate the natural history of disease, and identify those patients who could benefit from current or innovative therapeutic strategies. PMID:24532797

Testa, Francesco; Rossi, Settimio; Colucci, Raffaella; Gallo, Beatrice; Di Iorio, Valentina; della Corte, Michele; Azzolini, Claudio; Melillo, Paolo; Simonelli, Francesca

2014-01-01

244

Idiopathic macular telangiectasia type 2: ?the progressive vasculopathy.  

PubMed

Purpose. To describe the complete sequence of the progressive vasculopathy in macular telangiectasia type 2.?Methods. This is a report of a case demonstrating the complete vasogenic sequence in macular telangiectasia type 2 over the course of 15 years, and representative images from a collective of 150 patients with macular telangiectasia type 2 employing fundus photography, fluorescein angiography, and optical coherence tomography.?Results. Macular telangiectasia may progress along a predictable vasogenic sequence which consists of nonproliferative stages, characterized by temporal loss of macular luteopigment and inner retinal volume loss in the absence of vascular changes, followed by a progressive proliferative vasculopathy, first involving the deep capillary plexus with eventual extension of the vascular changes circumferentially in the inner retinal capillary plexus. Late proliferative stages may become indistinguishable from advanced neovascular age-related macular degeneration.?Conclusions. While it is rare to observe the complete vasogenic sequence of macular telangiectasia type 2, a classification into nonproliferative and proliferative stages can be established, and may prove helpful as the mechanisms driving the pathogenic process through those stages are identified. PMID:23138663

Engelbert, Michael; Yannuzzi, Lawrence A

2012-11-01

245

Visual pigment bleaching in isolated salamander retinal cones. Microspectrophotometry and light adaptation  

PubMed Central

Visual pigment bleaching desensitizes rod photoreceptors greatly in excess of that due to loss of quantum catch. Whether this phenomenon also occurs in cone photoreceptors was investigated for isolated salamander red-sensitive cones. In parallel experiments, (a) visual pigment depletion by steps of bleaching light was measured by microspectrophotometry, and (b) flash sensitivity was measured by recording light-sensitive membrane current. In isolated cones, visual pigment bleaching permanently reduced flash sensitivity significantly below that due to the reduction in quantum catch, and there was little spontaneous recovery of visual pigment. The "extra" desensitization due to bleaching was most prominent up to bleaches of approximately 80% visual pigment and reached a level approximately 1 log unit beyond that due to loss of quantum catch. At higher bleaches, the effect of loss of quantum catch became more important. Bleaching did not greatly reduce the maximum light-suppressible membrane current. A 99% reduction of the visual pigment permanently reduced the circulating current by only 30%. Visual pigment bleaching speeded up the kinetics of dim flash responses. All electrical effects of bleaching were reversed on exposure to 11-cis retinal, which probably caused visual pigment regeneration. Light adaptation in photopic vision is known to involve significant visual pigment depletion. The present results indicate that cones operate with a maintained circulating current even after a large pigment depletion. It is shown how Weber/Fechner behavior may still be observed in photopic vision when the contributions of bleaching to adaptation are included. PMID:8245820

1993-01-01

246

Peripapillary and Macular Choroidal Thickness in Glaucoma  

PubMed Central

Purpose To compare choroidal thickness (CT) between individuals with and without glaucomatous damage and to explore the association of peripapillary and submacular CT with glaucoma severity using spectral domain optical coherence tomography (SD-OCT). Methods Ninety-one eyes of 20 normal subjects and 43 glaucoma patients from the UCLA SD-OCT Imaging Study were enrolled. Imaging was performed using Cirrus HD-OCT. Choroidal thickness was measured at four predetermined points in the macular and peripapillary regions, and compared between glaucoma and control groups before and after adjusting for potential confounding variables. Results The average (± standard deviation) mean deviation (MD) on visual fields was ?0.3 (±2.0) dB in controls and ?3.5 (±3.5) dB in glaucoma patients. Age, axial length and their interaction were the most significant factors affecting CT on multivariate analysis. Adjusted average CT (corrected for age, axial length, their interaction, gender and lens status) however, was not different between glaucoma patients and the control group (P=0.083) except in the temporal parafoveal region (P=0.037); nor was choroidal thickness related to glaucoma severity (r=?0.187, P=0.176 for correlation with MD, r=?0.151, P=0.275 for correlation with average nerve fiber layer thickness). Conclusions Choroidal thickness of the macular and peripapillary regions is not decreased in glaucoma. Anatomical measurements with SD-OCT do not support the possible influence of the choroid on the pathophysiology of glaucoma.

Hosseini, Hamid; Nilforushan, Naveed; Moghimi, Sasan; Bitrian, Elena; Riddle, Jay; Lee, Gina Yoo; Caprioli, Joseph; Nouri-Mahdavi, Kouros

2014-01-01

247

The effects of polymer pigmentation on fingermark development techniques.  

PubMed

The effectiveness of latent fingerprint development techniques is heavily influenced by the physical and chemical properties of the deposition surface. The use of powder suspensions is increasing for development of prints on a range of surfaces. We demonstrate that carbon powder suspension development on polymers is detrimentally affected by the presence of common white pigment, titanium dioxide. Scanning electron microscopy demonstrates that patches of the compound are clearly associated with increased levels of powder adhesion. Substrates with nonlocalized titanium dioxide content also exhibit increased levels of carbon powder staining on a surface-wide basis. Secondary ion mass spectrometry and complementary techniques demonstrate the importance of levels of the pigment within the top 30 nm. The association is independent of fingermark deposition and may be related to surface energy variation. The detrimental effect of the pigment is not observed with small-particle reagent (MoS2 SPR) or cyanoacrylate (superglue) fuming techniques that exploit different development mechanisms. PMID:23822671

Bacon, Simon R; Ojeda, Jesus J; Downham, Rory; Sears, Vaughn G; Jones, Benjamin J

2013-11-01

248

Effect of Hemodialysis on Retinal Thickness in Patients with Diabetic Retinopathy, with and without Macular Edema, Using Optical Coherence Tomography  

PubMed Central

Background. Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear. Objective. To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD. Methods. Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD. Results. We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value—Kt/V, glycemic hemoglobin, or albumin levels before and after HD. Conclusions. HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study. PMID:25298889

Azem, Nur; Spierer, Oriel; Shaked, Meital; Neudorfer, Meira

2014-01-01

249

Microprobe analysis of chlorpromazine pigmentation  

SciTech Connect

We describe the histochemical, ultrastructural, and microanalytical features of a skin biopsy specimen obtained from a patient with chlorpromazine pigmentation. Golden-brown pigment granules were present in the dermis, predominantly in a perivascular arrangement. The granules stained positively with the Fontana-Masson stain for silver-reducing substances and negatively with Perl's stain for iron. Electron microscopy revealed dense inclusion bodies in dermal histiocytes, pericytes, endothelial cells, and Schwann cells, as well as lying free in the extracellular matrix. These ''chlorpromazine bodies'' were quite dense even in unosmicated, unstained ultrathin sections, indicating that the pigmentation is related, at least in part, to the inclusions. Microprobe analysis of the chlorpromazine bodies revealed a striking peak for sulfur, which strongly suggests the presence of the drug or its metabolite within these inclusions.

Benning, T.L.; McCormack, K.M.; Ingram, P.; Kaplan, D.L.; Shelburne, J.D.

1988-10-01

250

Differences in spectral absorption properties between active neovascular macular degeneration and mild age related maculopathy.  

PubMed

This study examines the differences in spectral absorption properties between the maculae of patients with active neovascular macular degeneration and those with early age related maculopathy (ARM). Patients attending for management of neovascular age related macular degeneration (AMD) underwent multispectral imaging with a system comprising of a modified digital fundus camera coupled with a 250-W tungsten-halogen lamp and a liquid crystal fast-tuneable filter. Images were obtained at 8 wavelengths between 496 and 700 nm. Aligned images were used to generate a DLA (differential light absorption, a measure of spectral absorption properties) map of the macular area. DLA maps were generated for both eyes of 10 sequential patients attending for anti-vascular endothelial growth factor injections. Each of these patients had active leaking neovascular AMD in one eye and early ARM or milder disease in the fellow eye. Eyes with neovascular AMD demonstrated lower average levels of DLA compared with their fellow eyes with early ARM (p=0.037, t test). The significant difference in DLA demonstrates the potential of multispectral imaging for differentiating the two pathologies non-invasively. PMID:23137662

Balaskas, Konstantinos; Nourrit, Vincent; Dinsdale, Michelle; Henson, David B; Aslam, Tariq

2013-05-01

251

Macular Oedema Related to Idiopathic Macular Telangiectasia Type 1 Treated with Dexamethasone Intravitreal Implant (Ozurdex)  

PubMed Central

A 65-year-old female presented with visual disturbance in her right eye lasting for over 2 months. Following investigations, she was diagnosed with MacTel type 1 in the right eye. Visual symptoms were refractory to initial treatment with intravitreal bevacizumab and thereafter intravtireal triamicinolone. The patient was then treated with Ozurdex, following which central macular thickness (CMT) decreased (from 397??m to 286??m) and visual acuity deteriorated (from logMAR 0.48 to 0.59). At 14 weeks posttreatment with Ozurdex, a recurrence of cystoid macular oedema (CMO) was observed. Following a second Ozurdex, visual acuity improved (from logMAR 0.7 to 0.64) and CMT decreased (from 349??m to 279??m). An additional recurrence of CMO was observed at eighteen weeks following the second Ozurdex. Following a third Ozurdex injection visual acuity deteriorated (from logMAR 0.74 to 0.78) and CMT decreased (from 332??m to 279??m). Conclusion. Treatment of macular oedema secondary to MacTel with Ozurdex demonstrated promising anatomical outcomes. However, visual outcomes continued to gradually deteriorate. PMID:25045562

Kamal, Ahmed

2014-01-01

252

Macular oedema related to idiopathic macular telangiectasia type 1 treated with dexamethasone intravitreal implant (ozurdex).  

PubMed

A 65-year-old female presented with visual disturbance in her right eye lasting for over 2 months. Following investigations, she was diagnosed with MacTel type 1 in the right eye. Visual symptoms were refractory to initial treatment with intravitreal bevacizumab and thereafter intravtireal triamicinolone. The patient was then treated with Ozurdex, following which central macular thickness (CMT) decreased (from 397??m to 286??m) and visual acuity deteriorated (from logMAR 0.48 to 0.59). At 14 weeks posttreatment with Ozurdex, a recurrence of cystoid macular oedema (CMO) was observed. Following a second Ozurdex, visual acuity improved (from logMAR 0.7 to 0.64) and CMT decreased (from 349??m to 279??m). An additional recurrence of CMO was observed at eighteen weeks following the second Ozurdex. Following a third Ozurdex injection visual acuity deteriorated (from logMAR 0.74 to 0.78) and CMT decreased (from 332??m to 279??m). Conclusion. Treatment of macular oedema secondary to MacTel with Ozurdex demonstrated promising anatomical outcomes. However, visual outcomes continued to gradually deteriorate. PMID:25045562

Loutfi, Mohamed; Papathomas, Thomas; Kamal, Ahmed

2014-01-01

253

Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions.  

PubMed

Breakdown of the inner endothelial blood-retinal barrier (BRB), as occurs in diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, uveitis and other chronic retinal diseases, results in vasogenic edema and neural tissue damage, causing loss of vision. The central mechanism of altered BRB function is a change in the permeability characteristics of retinal endothelial cells caused by elevated levels of growth factors, cytokines, advanced glycation end products, inflammation, hyperglycemia and loss of pericytes. Subsequently, paracellular but also transcellular transport across the retinal vascular wall increases via opening of endothelial intercellular junctions and qualitative and quantitative changes in endothelial caveolar transcellular transport, respectively. Functional changes in pericytes and astrocytes, as well as structural changes in the composition of the endothelial glycocalyx and the basal lamina around BRB endothelium further facilitate BRB leakage. As Starling's rules apply, active transcellular transport of plasma proteins by the BRB endothelial cells causing increased interstitial osmotic pressure is probably the main factor in the formation of macular edema. The understanding of the complex cellular and molecular processes involved in BRB leakage has grown rapidly in recent years. Although appropriate animal models for human conditions like diabetic macular edema are lacking, these insights have provided tools for rational design of drugs aimed at restoring the BRB as well as for design of effective transport of drugs across the BRB, to treat the chronic retinal diseases such as diabetic macular edema that affect the quality-of-life of millions of patients. PMID:23416119

Klaassen, Ingeborg; Van Noorden, Cornelis J F; Schlingemann, Reinier O

2013-05-01

254

Patterns of diabetic macular edema with optical coherence tomography  

Microsoft Academic Search

PURPOSE: We report cross-sectional images of diabetic macular edema and correlation between tomographic features and visual acuity with best correction by means of optical coherence tomography.METHOD: In a prospective study, optical coherence tomography was performed in 59 eyes of 42 patients with diabetic macular edema and in 10 eyes of 10 normal control subjects.RESULTS: Optical coherence tomography showed three patterns

Tomohiro Otani; Shoji Kishi; Yasuhiro Maruyama

1999-01-01

255

Age-related macular degeneration: a perspective on genetic studies  

Microsoft Academic Search

AimAge-related macular degeneration (AMD) is a common macular disease in the developed world and recent studies have shown that specific genes may be associated with it and may contribute to a higher risk of developing AMD.ObjectiveOur objective was to review systematically recent publications related to the genetics of AMD and provide relevant information that would help both scientists and clinicians

N Patel; T Adewoyin; N V Chong; Victor Chong

2008-01-01

256

Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cells.  

PubMed

The pathogenesis of age-related macular degeneration involves chronic oxidative stress, impaired degradation of membranous discs shed from photoreceptor outer segments and accumulation of lysosomal lipofuscin in retinal pigment epithelial (RPE) cells. It has been estimated that a major part of cellular proteolysis occurs in proteasomes, but the importance of proteasomes and the other proteolytic pathways including autophagy in RPE cells is poorly understood. Prior to proteolysis, heat shock proteins (Hsps), agents that function as molecular chaperones, attempt to refold misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. In the present study, the roles of the Hsp70 molecular chaperone and proteasomal and lysosomal proteolytic pathways were evaluated in human RPE cells (ARPE-19). The Hsp70 and ubiquitin protein levels and localization were analysed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. Hsp70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. The proteasome inhibitor MG-132 evoked the accumulation of perinuclear aggregates positive for Hsp70, ubiquitin-protein conjugates and the lysosomal membrane protein LAMP-2. Interestingly, the hsp70 mRNA depletion significantly increased cell death in conjunction with proteasome inhibition. We found that the accumulation of lysosomes was reversible: a cessation of proteasome inhibition led to clearance of the deposits via a mechanism believed to include autophagy. The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells. PMID:19017362

Ryhänen, Tuomas; Hyttinen, Juha M T; Kopitz, Jürgen; Rilla, Kirsi; Kuusisto, Erkki; Mannermaa, Eliisa; Viiri, Johanna; Holmberg, Carina I; Immonen, Ilkka; Meri, Seppo; Parkkinen, Jussi; Eskelinen, Eeva-Liisa; Uusitalo, Hannu; Salminen, Antero; Kaarniranta, Kai

2009-09-01

257

The role of pigmentation in face perception  

E-print Network

Faces each have distinct pigmentation as well as shape, which suggests that both cues may play a role in the perception of faces. However, there is a common implicit assumption that pigmentation cues are relatively ...

Russell, Richard (Richard P.)

2005-01-01

258

Case-control study of the risk factors for age related macular degeneration  

PubMed Central

AIM—A case-control study was initiated to determine the risk factors for the development of age related macular degeneration (AMD).?METHODS—Study participants, who were all white, aged 50-85 years, and were recruited from private ophthalmology practices. Each practitioner enrolled patients with bilateral AMD, who were then matched with controls for sex and age. Environmental factors and systemic and ocular histories were screened. All patients had bilateral red-free fundus photographs and fluorescein angiography. Photographs were classified into pigment epithelium alterations, drusen, geographic atrophy, and exudative AMD. Statistical analysis included the identification of risk factors for AMD. A multivariate analysis was performed at the end of the study. Analysis included the entire study population and was carried out for each stage of AMD.?RESULTS—1844 controls were compared with 1844 patients with AMD. Mean age was 71 years for controls and 72 for cases. Logistic regression identified six major risk factors for AMD (whole population): arterial hypertension (odds ratio (OR) =1.28), coronary disease (OR=1.31), hyperopia (OR=1.33), light coloured irises (OR=1.22), and lens opacities or previous cataract surgery (OR=1.55). The significance of vascular risk factors was increased for late stages of AMD, especially the atrophic forms (coronary disease, OR=3.19).?CONCLUSIONS—This large case-control study confirms some of the risk factors previously identified and may contribute to the determination of methods for prevention of AMD.?? Keywords: age related macular degeneration; risk factors; case-control study PMID:9893587

Chaine, G.; Hullo, A.; Sahel, J.; Soubrane, G.; Espinasse-Berrod, M.; Schutz, D.; Bourguignon, C.; Harpey, C.; Brault, Y.; Coste, M.; Moccatti, D.; Bourgeois, H.

1998-01-01

259

Automatic Detection of Diabetic Retinopathy and Age-Related Macular Degeneration in Digital Fundus Images  

PubMed Central

Purpose. To describe and evaluate the performance of an algorithm that automatically classifies images with pathologic features commonly found in diabetic retinopathy (DR) and age-related macular degeneration (AMD). Methods. Retinal digital photographs (N = 2247) of three fields of view (FOV) were obtained of the eyes of 822 patients at two centers: The Retina Institute of South Texas (RIST, San Antonio, TX) and The University of Texas Health Science Center San Antonio (UTHSCSA). Ground truth was provided for the presence of pathologic conditions, including microaneurysms, hemorrhages, exudates, neovascularization in the optic disc and elsewhere, drusen, abnormal pigmentation, and geographic atrophy. The algorithm was used to report on the presence or absence of disease. A detection threshold was applied to obtain different values of sensitivity and specificity with respect to ground truth and to construct a receiver operating characteristic (ROC) curve. Results. The system achieved an average area under the ROC curve (AUC) of 0.89 for detection of DR and of 0.92 for detection of sight-threatening DR (STDR). With a fixed specificity of 0.50, the system's sensitivity ranged from 0.92 for all DR cases to 1.00 for clinically significant macular edema (CSME). Conclusions. A computer-aided algorithm was trained to detect different types of pathologic retinal conditions. The cases of hard exudates within 1 disc diameter (DD) of the fovea (surrogate for CSME) were detected with very high accuracy (sensitivity = 1, specificity = 0.50), whereas mild nonproliferative DR was the most challenging condition (sensitivity= 0.92, specificity = 0.50). The algorithm was also tested on images with signs of AMD, achieving a performance of AUC of 0.84 (sensitivity = 0.94, specificity = 0.50). PMID:21666234

Barriga, E. Simon; Murray, Victor; Nemeth, Sheila; Crammer, Robert; Bauman, Wendall; Zamora, Gilberto; Pattichis, Marios S.; Soliz, Peter

2011-01-01

260

Prevention of age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

261

Prevention of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Koo, Simon Chi Yan; Chan, Clement Wai Nang

2010-01-01

262

Optical coherence tomography imaging of macular oedema  

PubMed Central

Macular oedema (ME) occurs in a wide variety of pathological conditions and accounts for different degrees of vision loss. Early detection of ME is therefore critical for diagnosis and therapeutic management. Optical coherence tomography (OCT) is a non-contact, diagnostic method that uses infrared light, which allows the analysis of the retinal structure by means of high-resolution tomographic cross sections. The identification, localisation, quantification and long-term follow-up of fluid collections are the most important capabilities of OCT. Since the introduction of OCT in clinical practice, it has become an invaluable diagnostic tool and different patterns of ME have been reported. The purpose of this manuscript is to review OCT profiles of ME according to the aetiology and describe what has been reported regarding intraretinal features in vivo. PMID:24934220

Trichonas, George; Kaiser, Peter K

2014-01-01

263

Optical coherence tomography classification of diabetic cystoid macular edema  

PubMed Central

Purpose To propose a new classification of diabetic cystoid macular edema (CME) based on optical coherence tomography (OCT) findings and cover all new important findings. Patients and methods A retrospective study was carried out in the El-Minia Investigation Eye Center between January 2012 and November 2012. It included 104 eyes of 86 patients, aged between 50 and 71 years, all with type II diabetes mellitus of duration from 5 to 20 years. All patients were diagnosed to have CME, as assessed by OCT, with measurement of the vertical size of the largest macular cyst and maximum macular thickness, and the relation between them. Results Patients were divided into four groups. Eyes with cysts less than 30% of macular thickness were considered to have CME I (n = 4, 3.84%), while those between 30% and 60% were considered to have CME II (n = 62, 59.62%). Eyes with cysts between 60% and 90% of macular thickness were considered to have CME III (n = 36, 34.62%). CME IV was diagnosed when the size of the cyst became more than 90% of the macular thickness, and this was encountered in two eyes (1.92%). Conclusions OCT is a useful technique for quantitative measurement and helps in better anatomical characterization of CME, and this classification of diabetic CME may be of value in classification of CME due to causes other than diabetes. PMID:24039393

Helmy, Yasser M; Allah, Heba R Atta

2013-01-01

264

Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease?  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch's membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis. PMID:24876950

2014-01-01

265

Perceptual learning in patients with macular degeneration  

PubMed Central

Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex. PMID:25368597

Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Ruhle, Sabine; Greenlee, Mark W.

2014-01-01

266

Effect of pigment volume concentration and latex particle size on pigment distribution  

Microsoft Academic Search

Pigment distribution in latex paints has been investigated by experiments using a combination of computer modelling, experimental model systems and pigmented paints. This paper deals with the geometric effects of variables such as pigment volume concentration and latex particle size on the pigment distribution in water-borne coatings. Physico-chemical effects, such as particle surface potentials and ionic strength of the serum,

Roger F. G. Brown; Christopher Carr; Michael E. Taylor

1997-01-01

267

21 CFR 178.3725 - Pigment dispersants.  

Code of Federal Regulations, 2011 CFR

... 2011-04-01 false Pigment dispersants. 178.3725 Section 178.3725...Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of...section may be safely used as pigment dispersants in food-contact materials. Substances...this chapter. Phosphorylated tall oil fatty acids (CAS Reg. No....

2011-04-01

268

21 CFR 178.3725 - Pigment dispersants.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2009-04-01 true Pigment dispersants. 178.3725 Section 178.3725...Production Aids § 178.3725 Pigment dispersants. Subject to the provisions of...section may be safely used as pigment dispersants in food-contact materials. Substances...this chapter. Phosphorylated tall oil fatty acids (CAS Reg. No....

2010-04-01

269

6 Nondestructive Estimation of Foliar Pigment  

E-print Network

by accurate measurements of the pigments present in plant leaves that play very important role in plant photosynthesis and protection. There are three major classes of pigments found in plants: chlorophylls141 6 Nondestructive Estimation of Foliar Pigment (Chlorophylls, Carotenoids, and Anthocyanins

Gitelson, Anatoly

270

Developmental Integration of Feather Growth and Pigmentation  

E-print Network

Developmental Integration of Feather Growth and Pigmentation and its Implications for the Evolution by coordinated pigmentation of thousands of growing feathers that vary in shape and size. Although the functional, specifically, the rules that link feather growth to pigment uptake and synthesis. Here, we combine biochemical

Badyaev, Alex

271

Polydimethylsiloxane as a substrate for retinal pigment epithelial cell growth.  

PubMed

Retinal pigment epithelial (RPE) cell transplantation represents potential treatment for age-related macular degeneration (AMD). Because delivery of isolated cells can cause serious complications, it is necessary to develop a suitable transplant membrane that could support an intact functioning RPE monolayer. Polydimethylsiloxane (PDMS) possesses the physical properties required for a transplanting device and is widely used clinically. We have investigated the use of PDMS as a potential surface for the growth of healthy RPE monolayers. PDMS discs were surface modified by air and ammonia gas plasma treatments. Dynamic contact angles were measured to determine the changes in wettability. Human ARPE-19 cells were seeded onto untreated and treated samples. Cell number, morphology and monolayer formation, cytotoxicity, and phagocytosis of photoreceptor outer segments (POS) were assessed at set time-points. Air plasma treatment increased the wettability of PDMS. This significantly enhanced cell growth, reaching confluence by day 7. Immunofluorescence revealed well-defined actin staining, monolayer formation, and high cell viability on air plasma treated and untreated surfaces, and to a lesser extent, on ammonia plasma treated. Furthermore, RPE monolayers were able to demonstrate phagocytosis of POS in a time-dependent manner similar to control. PDMS can support an intact functional monolayer of healthy differentiated RPE cells. PMID:17058209

Krishna, Yamini; Sheridan, Carl M; Kent, David L; Grierson, Ian; Williams, Rachel L

2007-03-01

272

Stem cells as source for retinal pigment epithelium transplantation.  

PubMed

Inherited maculopathies, age related macular degeneration and some forms of retinitis pigmentosa are associated with impaired function or loss of the retinal pigment epithelium (RPE). Among potential treatments, transplantation approaches are particularly promising. The arrangement of RPE cells in a well-defined tissue layer makes the RPE amenable to cell or tissue sheet transplantation. Different cell sources have been suggested for RPE transplantation but the development of a clinical protocol faces several obstacles. The source should provide a sufficient number of cells to at least recover the macula area. Secondly, cells should be plastic enough to be able to integrate in the host tissue. Tissue sheets should be considered as well, but the substrate on which RPE cells are cultured needs to be carefully evaluated. Immunogenicity can also be an obstacle for effective transplantation as well as tumorigenicity of not fully differentiated cells. Finally, ethical concerns may represent drawbacks when embryo-derived cells are proposed for RPE transplantation. Here we discuss different cell sources that became available in recent years and their different properties. We also present data on a new source of human RPE. We provide a protocol for RPE differentiation of retinal stem cells derived from adult ciliary bodies of post-mortem donors. We show molecular characterization of the in vitro differentiated RPE tissue and demonstrate its functionality based on a phagocytosis assay. This new source may provide tissue for allogenic transplantation based on best matches through histocompatibility testing. PMID:24933042

Bertolotti, Evelina; Neri, Alberto; Camparini, Monica; Macaluso, Claudio; Marigo, Valeria

2014-09-01

273

The genetic basis of divergent pigment patterns in juvenile threespine sticklebacks  

PubMed Central

Animal pigment patterns are important for a range of functions, including camouflage and communication. Repeating pigment patterns, such as stripes, bars and spots have been of particular interest to developmental and theoretical biologists, but the genetic basis of natural variation in such patterns is largely unexplored. In this study, we identify a difference in a periodic pigment pattern among juvenile threespine sticklebacks (Gasterosteus aculeatus) from different environments. Freshwater sticklebacks exhibit prominent vertical bars that visually break up the body shape, but sticklebacks from marine populations do not. We hypothesize that these distinct pigment patterns are tuned to provide crypsis in different habitats. This phenotypic difference is widespread and appears in most of the freshwater populations that we sampled. We used quantitative trait locus (QTL) mapping in freshwater–marine F2 hybrids to elucidate the genetic architecture underlying divergence in this pigmentation pattern. We identified two QTL that were significantly associated with variation in barring. Interestingly, these QTL were associated with two distinct aspects of the pigment pattern: melanophore number and overall pigment level. We compared the QTL locations with positions of known pigment candidate genes in the stickleback genome. We also identified two major QTL for juvenile body size, providing new insights into the genetic basis of juvenile growth rates in natural populations. In summary, although there is a growing literature describing simple genetic bases for adaptive coloration differences, this study emphasizes that pigment patterns can also possess a more complex genetic architecture. PMID:21304547

Greenwood, A K; Jones, F C; Chan, Y F; Brady, S D; Absher, D M; Grimwood, J; Schmutz, J; Myers, R M; Kingsley, D M; Peichel, C L

2011-01-01

274

Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography.  

PubMed

We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures' tissue-inherent polarization properties. PMID:21198152

Baumann, Bernhard; Gotzinger, Erich; Pircher, Michael; Sattmann, Harald; Schuutze, Christopher; Schlanitz, Ferdinand; Ahlers, Christian; Schmidt-Erfurth, Ursula; Hitzenberger, Christoph K

2010-01-01

275

Segmentation and quantification of retinal lesions in age-related macular degeneration using polarization-sensitive optical coherence tomography  

PubMed Central

We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures’ tissue-inherent polarization properties. PMID:21198152

Baumann, Bernhard; Gotzinger, Erich; Pircher, Michael; Sattmann, Harald; Schutze, Christopher; Schlanitz, Ferdinand; Ahlers, Christian; Schmidt-Erfurth, Ursula; Hitzenberger, Christoph K.

2011-01-01

276

Nano chitosan peptide as a potential therapeutic carrier for retinal delivery to treat age-related macular degeneration  

PubMed Central

Purpose We describe the synthesis and use of an efficient nano carrier molecule for retinal delivery of a nano chitosan peptide that has potential application for treating age-related macular degeneration (AMD). We chose serine-threonine-tyrosine as the peptide sequence because it is well known to act as a transduction signaling agent within and between retinal pigmented epithelium cells. Methods A nanoformulation of a water-soluble chitosan conjugated with a peptide (serine-threonine-tyrosine) was synthesized by a method developed in our laboratory and characterized with dynamic light scattering, zeta potential, transmission electron microscopy, nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The in vitro efficacy of the formulation was evaluated in retinal cells with confocal microscopy by studying the formulation’s action on tyrosine kinase activity. Results The conjugated nano chitosan peptide showed evidence of tyrosine kinase activity as seen by fluorescent signals under confocal microscopy, while nano chitosan or peptide alone did not show such activity. Conclusions Conjugated nano chitosan peptide may promote binding and engulfment. This molecule is an excellent carrier for retinal drug delivery and has the potential to treat age-related macular degeneration. PMID:22977298

Jayaraman, Melamangalam S.; Bharali, Dhruba J.; Sudha, Thangirala

2012-01-01

277

Induced pigmentation in zooplankton: a trade-off between threats from predation and ultraviolet radiation.  

PubMed Central

Ultraviolet (UV) radiation is harmful to all life, and the ongoing depletion of the ozone layer is likely to affect interactions among both terrestrial and aquatic organisms. Some organisms have evolved adaptations to reduce radiation damage, such as the various types of protective pigmentation of freshwater zooplankton. However, strong pigmentation also increases vulnerability to visually hunting predators. Hence, where both UV radiation and predation are intense, zooplankton may be sandwiched between conflicting selective pressures: to be pigmented and to be transparent at the same time. Here, I show that the level of pigmentation in copepods is up to ten times higher in lakes without predatory fishes than where fishes are present. Moreover, animals from the same population exposed to either UV light or predator scent showed a 10% difference in pigmentation after only four days, suggesting that pigmentation is an inducible trait. Hence, individual copepods are not passive victims of selective predation or radiation damage, but adjust the level of pigmentation according to the prevailing threat. The ability to adjust pigmentation level rapidly may be especially useful in situations where risk assessment is difficult due to strong seasonal and spatial variation in risk variables, such as in Arctic regions. With progressive thinning of the ozone layer, the ability of some but not other organisms to adjust protection against UV radiation may lead to counter-intuitive, large-scale alterations in freshwater food webs. PMID:11413651

Hansson, L A

2000-01-01

278

Induced pigmentation in zooplankton: a trade-off between threats from predation and ultraviolet radiation.  

PubMed

Ultraviolet (UV) radiation is harmful to all life, and the ongoing depletion of the ozone layer is likely to affect interactions among both terrestrial and aquatic organisms. Some organisms have evolved adaptations to reduce radiation damage, such as the various types of protective pigmentation of freshwater zooplankton. However, strong pigmentation also increases vulnerability to visually hunting predators. Hence, where both UV radiation and predation are intense, zooplankton may be sandwiched between conflicting selective pressures: to be pigmented and to be transparent at the same time. Here, I show that the level of pigmentation in copepods is up to ten times higher in lakes without predatory fishes than where fishes are present. Moreover, animals from the same population exposed to either UV light or predator scent showed a 10% difference in pigmentation after only four days, suggesting that pigmentation is an inducible trait. Hence, individual copepods are not passive victims of selective predation or radiation damage, but adjust the level of pigmentation according to the prevailing threat. The ability to adjust pigmentation level rapidly may be especially useful in situations where risk assessment is difficult due to strong seasonal and spatial variation in risk variables, such as in Arctic regions. With progressive thinning of the ozone layer, the ability of some but not other organisms to adjust protection against UV radiation may lead to counter-intuitive, large-scale alterations in freshwater food webs. PMID:11413651

Hansson, L A

2000-11-22

279

Evolution of dim-light and color vision pigments.  

PubMed

A striking level of diversity of visual systems in different species reflects their adaptive responses to various light environments. To study the adaptive evolution of visual systems, we need to understand how visual pigments, the light-sensitive molecules, have tuned their wavelengths of light absorption. The molecular basis of spectral tuning in visual pigments, a central unsolved problem in phototransduction, can be understood only by studying how different species have adapted to various light environments. Certain amino acid replacements at 30 residues explain some dim-light and color vision in vertebrates. To better understand the molecular and functional adaptations of visual pigments, we must identify all critical amino acid replacements that are involved in the spectral tuning and elucidate the effects of their interactions on the spectral shifts. PMID:18544031

Yokoyama, Shozo

2008-01-01

280

Age-related macular degeneration: Beyond anti-angiogenesis  

PubMed Central

Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate vascular maturation, rather than its arrest or destruction. This would neutralize hypoxia, thus removing the stimulus that drives neovascularization and in turn the need for repeated lifelong intravitreal therapy. A pro-angiogenic approach would eliminate neovascular leakage and ultimately complete repair and preserve the neurosensory retina. PMID:24426775

2014-01-01

281

Temporal Macular Thinning Associated With X-Linked Alport Syndrome  

PubMed Central

Importance Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS). Objectives To report OCT findings and severity of temporal macular thinning in a cohort with XLAS and to correlate these and other ocular findings with mutation genotype. Design Patients with XLAS underwent genotyping for COL4A5 mutations and complete eye examinations with retinal imaging using spectral domain OCT and fundus photography. Temporal macular thinning was calculated from OCT measurements by comparing the ratio of the retinal thickness of the temporal to the nasal subfields with a published normative database. Setting University departments of ophthalmology and nephrology. Participants Thirty-two patients from 24 families. Main Outcome and Measures Temporal thinning index calculated from spectral domain OCT scans. Results All study patients had a mutation associated with the X-linked COL4A5 gene. Eleven different mutations were identified. Eleven of 32 patients (34%) expressed the L1649R mutation. Of a total of 63 eyes with available OCT scans, 44 (70%) had severe pathological temporal macular thinning. The L1649R mutation was associated with the least amount of severe temporal macular thinning and later onset of renal failure. Conclusions and Relevance Temporal macular thinning is a prominent sign associated with XLAS, suggesting that OCT measurements are essential in the diagnosis and prognosis of the disease. The L1649R mutation in the COL4A5 gene causes a relatively mild form of XLAS characterized by late-onset renal failure and less frequent, severe temporal macular thinning relative to other COL4A5 mutations. The pathological basis for the retinal abnormalities of XLAS remains to be established. PMID:23572034

Ahmed, Faisal; Kamae, Kandon K.; Jones, Denise J.; DeAngelis, Margaret M.; Hageman, Gregory S.; Gregory, Martin C.; Bernstein, Paul S.

2013-01-01

282

Computational assessment of effective dose and patient specific doses for kilovoltage stereotactic radiosurgery of wet age-related macular degeneration  

NASA Astrophysics Data System (ADS)

Age-related macular degeneration (AMD) is a leading cause of vision loss and a major health problem for people over the age of 50 in industrialized nations. The current standard of care, ranibizumab, is used to help slow and in some cases stabilize the process of AMD, but requires frequent invasive injections into the eye. Interest continues for stereotactic radiosurgery (SRS), an option that provides a non-invasive treatment for the wet form of AMD, through the development of the IRay(TM) (Oraya Therapeutics, Inc., Newark, CA). The goal of this modality is to destroy choroidal neovascularization beneath the pigment epithelium via delivery of three 100 kVp photon beams entering through the sclera and overlapping on the macula delivering up to 24 Gy of therapeutic dose over a span of approximately 5 minutes. The divergent x-ray beams targeting the fovea are robotically positioned and the eye is gently immobilized by a suction-enabled contact lens. Device development requires assessment of patient effective dose, reference patient mean absorbed doses to radiosensitive tissues, and patient specific doses to the lens and optic nerve. A series of head phantoms, including both reference and patient specific, was derived from CT data and employed in conjunction with the MCNPX 2.5.0 radiation transport code to simulate treatment and evaluate absorbed doses to potential tissues-at-risk. The reference phantoms were used to evaluate effective dose and mean absorbed doses to several radiosensitive tissues. The optic nerve was modeled with changeable positions based on individual patient variability seen in a review of head CT scans gathered. Patient specific phantoms were used to determine the effect of varying anatomy and gaze. The results showed that absorbed doses to the non-targeted tissues were below the threshold levels for serious complications; specifically the development of radiogenic cataracts and radiation induced optic neuropathy (RON). The effective dose determined (0.29 mSv) is comparable to diagnostic procedures involving the head, such as an x-ray or CT scan. Thus, the computational assessment performed indicates that a previously established therapeutic dose can be delivered effectively to the macula with IRay(TM) without the potential for secondary complications.

Hanlon, Justin Mitchell

283

In vitro inhibition of pigmentation and fiber development in colored cotton.  

PubMed

Colored cotton has naturally pigmented fibers. The mechanism of pigmentation in cotton fiber is not well documented. This experiment was conducted to study the effects of respiratory chain inhibitors, i.e., rotenone and thiourea, on pigmentation and fiber development in colored cotton. After 1 d post-anthesis, ovaries were harvested and developing ovules were cultured on the liquid medium containing different concentrations of rotenone and thiourea for 30 d. The results demonstrate that both respiratory inhibitors reduced fiber length and ovule development under ovule culture conditions, and the inhibition efficiency of rotenone was much higher than that of thiourea. Rotenone and thiourea also showed significant effects on fiber pigment (color) development in colored cotton. In green cotton fiber, rotenone advanced fiber pigment development by 7 d at 200 ?mol/L, while thiourea inhibited fiber pigmentation at all treatment levels (400, 600, 800, 1000, and 2000 ?mol/L). Both respiratory inhibitors, however, had no significant effects on pigmentation of brown cotton fibers. The activities of cytochrome c oxidase (COX) and polyphenol oxidase (PPO) decreased significantly with increasing levels of both respiratory inhibitors. It is suggested that both respiratory inhibitors have important roles in deciphering the mechanism of pigmentation and fiber development in colored cotton. PMID:22661210

Yuan, Shu-na; Malik, Waqas; Hua, Shui-jin; Bibi, Noreen; Wang, Xue-de

2012-06-01

284

Selective Cone Photoreceptor Injury in Acute Macular Neuroretinopathy  

PubMed Central

Purpose To evaluate retinal structural and functional abnormalities in a patient with Acute Macular Neuroretinopathy (AMN). Methods An adaptive optics scanning light ophthalmoscope (AOSLO) was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral domain optical coherence tomography (SD-OCT) was used to examine retinal lamination. Microperimetry was used to assess function across the macula. Results Microperimetry showed reduced function of localized areas within retinal lesions corresponding to subjective scotomas. SD-OCT imaging revealed attenuation of two outer retinal bands typically thought to reflect photoreceptor structure. AOSLO images of the photoreceptor mosaic revealed a heterogeneous presentation within these lesions. There were areas containing non-waveguiding cones and other areas of decreased cone density where the remaining rods had expanded to fill in the vacant space. Within these lesions, cone densities were shown to be significantly lower than eccentricity matched areas of normal retina, as well as accepted histological measurements. A 6-month follow up revealed no change in rod or cone structure. Conclusions Imaging of AMN using an AOSLO shows a preferential disruption of cone photoreceptor structure within the region of decreased retinal sensitivity (as measured by microperimetry). AO-based imaging tools provide a noninvasive way to assess photoreceptor structure at a level of detail that is not resolved by use of conventional SD-OCT or other clinical measures. PMID:23615345

Hansen, Sean O.; Cooper, Robert F.; Dubra, Alfredo; Carroll, Joseph; Weinberg, David V.

2014-01-01

285

Pigmented paravenous retinochoroidal atrophy (Review)  

PubMed Central

Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon disease characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinochoroidal atrophy that are distributed along the retinal veins. Patients are usually asymptomatic and the disease process is non-progressive or slow and subtly progressive. It is commonly bilateral and symmetric. The cause of the condition may be unknown or idiopathic, although a dysgenetic, degenerative, hereditary etiology or even an inflammatory cause has been hypothesized. A non-inflammatory cause is referred to as primary, while inflammation-associated PPRCA is referred to as secondary or pseudo PPRCA. The present study reviewed and summarized the features of PPRCA. PMID:24926324

HUANG, HOU-BIN; ZHANG, YI-XIN

2014-01-01

286

Human skin pigmentation, migration and disease susceptibility  

PubMed Central

Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D3. Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre-vitamin D3 under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples—nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)—are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century. PMID:22312045

Jablonski, Nina G.; Chaplin, George

2012-01-01

287

Willemite pigments with nio additions  

Microsoft Academic Search

of pigments and their formation reaction. In the experimental mixtures we replaced ZnO, present in the composition of wfllemite, by NiO in amounts of from 0.05 to 1 mole. The synthesis was accomplished by solid phase sintering. The salts and oxides in certain stoichiometric ratios were blended in the moist state (porcelain grinder on glass), and the resulting paste after

G. N. Maslennikova; A. I. Glebycheva; N. P. Fomina

1974-01-01

288

Unilateral macular edema with central retinal vein occlusion in systemic lupus erythematosus: a case report  

PubMed Central

Central retinal vein occlusion (CRVO) is frequent in patients with systemic lupus erythematosus (SLE), but the treatment of the macular edema with this disease is extremely difficult. We report a case of cystoid macular edema (CME) secondary to unilateral CRVO in a patient with SLE that responded to intravitreous injection of an anti-vascular endothelial growth factor (VEGF) agent. A 33-year-old Japanese woman was referred to our department with unilateral impairment of vision. Microperimetry (MP-1) showed a cessation of foveal sensitivity. Fluorescein angiography showed CME without ischaemia of the macular region or peripheral retina (nonischemic CRVO). A diagnosis of CME and unilateral nonischemic CRVO combined with SLE was made and intravitreous anti-VEGF therapy was given. A sample of aqueous humor was harvested at the start of intravitreous injection after obtaining informed consent. Then the levels of VEGF and monocyte chemotactic protein (MCP)-1 were measured in the aqueous humor by enzyme-linked immunosorbent assay, revealing that VEGF was 234 pg/mL and MCP-1 was 501 pg/mL. Two weeks later, left eye vision improved to 20/20. Optical coherence tomography (OCT) showed considerable amelioration of retinal swelling and CME. MP-1 showed a marked increase of foveal sensitivity. However, she had recurrence of edema 3 months later. After harvesting aqueous humor again, intravitreous injection of an anti-VEGF agent was repeated for CME. The aqueous VEGF and MCP-1 levels were 156 pg/mL and 360 pg/mL, respectively. These findings suggest that inflammation was improved by intravitreous injection of bevacizumab. Intravitreous injection of anti-VEGF agents may be effective for CME due to nonischemic CRVO in SLE patients if their inflammatory factor levels are low. PMID:23690676

Noma, Hidetaka; Shimizu, Hiroshi; Mimura, Tatsuya

2013-01-01

289

Indocyanine green staining and removal of internal limiting membrane in macular hole surgery: histology and outcome  

Microsoft Academic Search

PURPOSE: To report the surgical technique, outcome, and histologic findings involving indocyanine green staining and removal of internal limiting membrane in primary macular hole surgery.METHODS: Prospectively, consecutive patients with idiopathic macular hole or myopic macular hole with retinal detachment were recruited. After pars plana vitrectomy and epiretinal membrane removal, the internal limiting membrane was stained and removed. The specimens were

Alvin K. H Kwok; Winnie W. Y Li; C. P Pang; Timothy Y. Y Lai; Gary H. F Yam; Nongnart R Chan; Dennis S. C Lam

2001-01-01

290

Changes of macular sensitivity and morphology after pars plana vitrectomy for macular edema with central retinal vein occlusion: a case series  

PubMed Central

Background It is unclear how retinal ischemia influences the changes of visual acuity, macular sensitivity, macular thickness, and macular volume after the performance of pars plana vitrectomy (PPV) for macular edema in patients with central retinal vein occlusion (CRVO). Methods Ten patients (10 eyes) with CRVO and macular edema underwent PPV. Retinal ischemia was evaluated from the area of capillary nonperfusion on fluorescein angiography, and the patients were classified into ischemic or nonischemic groups. Microperimetry was performed with a Micro Perimeter 1. Macular thickness and volume were measured by optical coherence tomography. Results In both groups, the mean macular thickness within the central 4°, 10°, and 20° fields decreased significantly from baseline to 3 and 6 months after PPV (all P?macular sensitivity within the central 4°, 10°, and 20° fields increased from baseline to 3 and 6 months after PPV, but no significant difference was observed. Conclusions These results suggest that PPV may be effective for improving macular thickness, volume, and sensitivity in patients with macular edema secondary to ischemic CRVO, although there was no significant difference. PMID:23379834

2013-01-01

291

Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium  

PubMed Central

Controlling the differentiation of human pluripotent stem cells is the goal of many laboratories, both to study normal human development and to generate cells for transplantation. One important cell type under investigation is the retinal pigmented epithelium (RPE). Age-related macular degeneration (AMD), the leading cause of blindness in the Western world, is caused by dysfunction and death of the RPE. Currently, RPE derived from human embryonic stem cells are in clinical trials for the treatment of AMD. Although protocols to generate RPE from human pluripotent stem cells have become more efficient since the first report in 2004, they are still time-consuming and relatively inefficient. We have found that the addition of defined factors at specific times leads to conversion of approximately 80% of the cells to an RPE phenotype in only 14 days. This protocol should be useful for rapidly generating RPE for transplantation as well as for studying RPE development in vitro. PMID:23599499

Buchholz, David E.; Pennington, Britney O.; Croze, Roxanne H.; Hinman, Cassidy R.

2013-01-01

292

The genomic response of the retinal pigment epithelium to light damage and retinal detachment  

PubMed Central

The retinal pigment epithelium (RPE) plays an essential role in maintaining the health of the retina. The RPE is also the site of pathologic processes in a wide variety of retinal disorders including monogenic retinal dystrophies, age-related macular degeneration, and retinal detachment. Despite intense interest in the RPE, little is known about its molecular response to ocular damage or disease. We have conducted a comprehensive analysis of changes in transcript abundance (the “genomic response”) in the murine RPE following light damage. Several dozen transcripts, many related to cell-cell signaling, show significant increases in abundance in response to bright light; transcripts encoding visual cycle proteins show a decrease in abundance. Similar changes are induced by retinal detachment. Environmental and genetic perturbations that modulate the RPE response to bright light suggest that this response is controlled by the retina. In contrast to the response to bright light, the RPE response to retinal detachment over-rides these modulatory affects. PMID:18815272

Rattner, Amir; Toulabi, Leila; Williams, John; Yu, Huimin; Nathans, Jeremy

2008-01-01

293

C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration  

Microsoft Academic Search

BackgroundThere is increasing evidence that inflammation and immune-mediated processes (complement activation) play an important role in age-related macular degeneration (AMD) pathogenesis. A genetic variation in the gene encoding complement factor H (CFH) and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have consistently been shown to be associated with an increased risk for AMD. In the

Imran A Bhutto; Takayuki Baba; Carol Merges; Vikash Juriasinghani; D Scott McLeod; Gerard A Lutty

2011-01-01

294

Difficulty in performing everyday activities in patients with juvenile macular dystrophies: comparison with patients with retinitis pigmentosa  

Microsoft Academic Search

AIMSTo ascertain the level of perceived difficulty experienced by patients with central vision loss due to juvenile macular dystrophies in the performance of everyday activities. A second objective was to compare their perceived difficulty with that of patients with retinitis pigmentosa (RP) with primarily peripheral vision loss.METHODS72 patients with Stargardt disease, cone dystrophy, or cone-rod dystrophy who had visual acuities

Janet P Szlyk; Gerald A Fishman; Sandeep Grover; Beatrise I Revelins; Deborah J Derlacki

1998-01-01

295

Expression of Pigment Cell-Specific Genes in the Ontogenesis of the Sea Urchin Strongylocentrotus intermedius  

PubMed Central

One of the polyketide compounds, the naphthoquinone pigment echinochrome, is synthesized in sea urchin pigment cells. We analyzed polyketide synthase (pks) and sulfotransferase (sult) gene expression in embryos and larvae of the sea urchin Strongylocentrotus intermedius from various stages of development and in specific tissues of the adults. We observed the highest level of expression of the pks and sult genes at the gastrula stage. In unfertilized eggs, only trace amounts of the pks and sult transcripts were detected, whereas no transcripts of these genes were observed in spermatozoids. The addition of shikimic acid, a precursor of naphthoquinone pigments, to zygotes and embryos increased the expression of the pks and sult genes. Our findings, including the development of specific conditions to promote pigment cell differentiation of embryonic sea urchin cells in culture, represent a definitive study on the molecular signaling pathways that are involved in the biosynthesis of pigments during sea urchin development. PMID:21804858

Ageenko, Natalya V.; Kiselev, Konstantin V.; Odintsova, Nelly A.

2011-01-01

296

Expression of Pigment Cell-Specific Genes in the Ontogenesis of the Sea Urchin Strongylocentrotus intermedius.  

PubMed

One of the polyketide compounds, the naphthoquinone pigment echinochrome, is synthesized in sea urchin pigment cells. We analyzed polyketide synthase (pks) and sulfotransferase (sult) gene expression in embryos and larvae of the sea urchin Strongylocentrotus intermedius from various stages of development and in specific tissues of the adults. We observed the highest level of expression of the pks and sult genes at the gastrula stage. In unfertilized eggs, only trace amounts of the pks and sult transcripts were detected, whereas no transcripts of these genes were observed in spermatozoids. The addition of shikimic acid, a precursor of naphthoquinone pigments, to zygotes and embryos increased the expression of the pks and sult genes. Our findings, including the development of specific conditions to promote pigment cell differentiation of embryonic sea urchin cells in culture, represent a definitive study on the molecular signaling pathways that are involved in the biosynthesis of pigments during sea urchin development. PMID:21804858

Ageenko, Natalya V; Kiselev, Konstantin V; Odintsova, Nelly A

2011-01-01

297

Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration.  

PubMed

This work presents a combined light and electron microscopical approach to investigate the initial breakdown of the retinal pigment epithelium (RPE) and choriocapillaris (CC) in age-related macular degeneration (AMD). Perimacular sections of 12 dry and wet AMD eyes (82 ± 15 years) and 7 age-matched controls (75 ± 10 years) without retinal pathology were investigated. Disease progression was classified into 5 stages of retinal degeneration to investigate the concurrent CC breakdown. Special emphasis was laid on transitions where intact CC-RPE-retina complexes went over into highly atrophied areas. AMD sections showed elevated loss of photoreceptors, RPE and CC (p < 0.01), and thickened Bruch's membrane with increased basal laminar and linear deposits compared with controls. Up to 27% of the CC was lost in controls although RPE and retina were still intact. This primary loss of CC further increased with AMD (up to 100%). The data implicate that CC breakdown already occurs during normal aging and precedes degeneration of the RPE and retina with AMD, defining AMD as a vascular disease. Particular attention should be given to the investigation of early AMD stages and transitional stages to the late stage that reveal a possible sequence of degenerative steps with aging and AMD. PMID:24925811

Biesemeier, Antje; Taubitz, Tatjana; Julien, Sylvie; Yoeruek, Efdal; Schraermeyer, Ulrich

2014-11-01

298

Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia  

PubMed Central

Aims To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Methods Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. Results On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. Conclusions This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented. PMID:22976584

Cherepanoff, Svetlana; Killingsworth, Murray C; Zhu, Meidong; Nolan, Timothy; Hunyor, Alex P; Young, Stephanie H; Hageman, Gregory S; Gillies, Mark C

2012-01-01

299

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.  

PubMed

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness. PMID:21297615

Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D; Fowler, Benjamin J; Cho, Won Gil; Kleinman, Mark E; Ponicsan, Steven L; Hauswirth, William W; Chiodo, Vince A; Karikó, Katalin; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W; Braun, Robert E; Hinton, David R; Zhang, Qing; Grossniklaus, Hans E; Provis, Jan M; Madigan, Michele C; Milam, Ann H; Justice, Nikki L; Albuquerque, Romulo J C; Blandford, Alexander D; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R; Ambati, Balamurali K; Rudin, Charles M; Chong, Mark M W; Provost, Patrick; Kugel, Jennifer F; Goodrich, James A; Dunaief, Joshua L; Baffi, Judit Z; Ambati, Jayakrishna

2011-03-17

300

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration  

PubMed Central

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell death. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness. PMID:21297615

Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D.; Fowler, Benjamin J.; Cho, Won Gil; Kleinman, Mark E.; Ponicsan, Steven L.; Hauswirth, William W.; Chiodo, Vince A.; Karikó, Katalin; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W.; Braun, Robert E.; Hinton, David R.; Zhang, Qing; Grossniklaus, Hans E.; Provis, Jan M.; Madigan, Michele C.; Milam, Ann H.; Justice, Nikki L.; Albuquerque, Romulo J.C.; Blandford, Alexander D.; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R.; Ambati, Balamurali K.; Rudin, Charles M.; Chong, Mark M.W.; Provost, Patrick; Kugel, Jennifer F.; Goodrich, James A.; Dunaief, Joshua L.; Baffi, Judit Z.; Ambati, Jayakrishna

2011-01-01

301

Induced Pluripotent Stem Cell Therapies for Geographic Atrophy of Age-Related Macular Degeneration  

PubMed Central

There is currently no FDA-approved therapy for treating patients with geographic atrophy (GA), a late stage of age-related macular degeneration (AMD). Cell transplantation has the potential to restore vision in these patients. This review discusses how recent advancement in induced pluripotent stem (iPS) cells provides a promising therapy for GA treatment. Recent advances in stem cell biology have demonstrated that it is possible to derive iPS cells from human somatic cells by introducing reprogramming factors. Human retinal pigment epithelium (RPE) cells and photoreceptors can be derived from iPS cells by defined factors. Studies show that transplanting these cells can stabilize or recover vision in animal models. However, cell derivation protocols and transplantation procedures still need to be optimized. Much validation has to be done before clinical-grade, patient-derived iPS can be applied for human therapy. For now, RPE cells and photoreceptors derived from patient-specific iPS cells can serve as a valuable tool in elucidating the mechanism of pathogenesis and drug discovery for GA. PMID:21609235

Du, Hongjun; Lim, Siok Lam; Grob, Seanna; Zhang, Kang

2013-01-01

302

Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD. PMID:24707498

Vereb, Zoltan; Facsko, Andrea; Kaarniranta, Kai

2014-01-01

303

Quantitative genetics of pigmentation development in 2 populations of the common garter snake, Thamnophis sirtalis.  

PubMed

The evolutionary importance of ontogenetic change has been noted since Darwin. However, most analyses of phenotypic evolution focus on single landmark ages. Here, we present an inheritance study that quantifies genetic variation in pigmentation across early-age (i.e., birth to 180 days) development in 2 populations of the common garter snake, Thamnophis sirtalis. The populations are phenotypically distinct and geographically isolated (Manitoba, CA and Northern California, USA). There were highly significant differences between populations for the developmental trajectory of mean pigmentation, with the Manitoba population exhibiting a mean pigmentation level that increased across ontogeny, whereas the California population exhibited mean pigmentation that was invariant across ontogeny. Subsequent quantitative genetic analyses revealed heritable variation at all ages in Manitoba but low levels of phenotypic and genetic variation in California at all ages. A quantitative genetic decomposition of the longitudinal genetic variance-covariance matrix for the age-specific pigmentation phenotypes in the Manitoba population revealed 2 primary orthogonal axes that explained most ( approximately 100%) of the pigmentation variation across ontogeny. The primary axis, explaining 93% of the genetic variation, is an axis of genetic variation whose principal value loadings change from positive to negative across development, suggesting that the most rapid evolutionary response to selection on pigmentation variation will occur in the direction characterized by a tradeoff in early-age versus late-age pigmentation phenotypes. Pigmentation is known to be ecologically important and subject to rapid evolution under selection. Our study shows that significant differences exist between these 2 populations for their capacity to respond to selection on pigmentation which is not only influenced by the population of origin but also by the developmental process. We suggest that developmental timing may be a potential explanatory mechanism for the difference between the populations. PMID:20453034

Westphal, Michael F; Morgan, Theodore J

2010-01-01

304

Progressive Macular Hypomelanosis in Korean Patients: A Clinicopathologic Study  

PubMed Central

Background Progressive macular hypomelanosis is characterized by ill-defined, non-scaly, hypopigmented macules primarily on the trunk of the body. Although numerous cases of progressive macular hypomelanosis have been reported, there have been no clinicopathologic studies of progressive macular hypomelanosis in Korean patients. Objective In this study we examined the clinical characteristics, histologic findings, and treatment methods for progressive macular hypomelanosis in a Korean population. Methods Between 1996 and 2005, 20 patients presented to the Department of Dermatology at Busan Paik Hospital with acquired, non-scaly, confluent, hypopigmented macules on the trunk, and with no history of inflammation or infection. The medical records, clinical photographs, and pathologic findings for each patient were examined. Results The patients included 5 men and 15 women. The mean age of onset was 21.05±3.47 years. The back was the most common site of involvement. All KOH examinations were negative. A Wood's lamp examination showed hypopigmented lesions compared with the adjacent normal skin. A microscopic examination showed a reduction in the number of melanin granules in the lesions compared with the adjacent normal skin, although S-100 immunohistochemical staining did not reveal significant differences in the number of melanocytes. Among the 20 patients, 7 received topical drug therapy, 6 were treated with narrow-band ultraviolet B phototherapy, 4 received oral minocycline, and 3 did not receive any treatment. Conclusion Most of the patients with progressive macular hypomelanosis had asymptomatic ill-defined, non-scaly, and symmetric hypopigmented macules, especially on the back and abdomen. Histologically, the number of melanocytes did not differ significantly between the hypopigmented macules and the normal perilesional skin. No effective treatment is known for progressive macular hypomelanosis; however, narrow-band ultraviolet B phototherapy may be a useful treatment modality. PMID:20523800

Hwang, Seon Wook; Hong, Soon Kwon; Kim, Sang Hyun; Park, Jeong Hoon; Seo, Jong Keun; Sung, Ho Suk

2009-01-01

305

Cerium molybdenum oxides for environmentally benign pigments  

Microsoft Academic Search

A new class of environmentally benign yellow rare earth pigments as alternatives to lead, cadmium and chromium pigments is presented. These pigments are based on cerium molybdenum oxides corresponding to the structural formulae NaCe0.5(MoO4) and Ce(MoO4)2. The coloring properties of the compositions prepared by varying the Ce:Mo ratio in the presence and absence of phosphates have been evaluated. The reflectance

Kalarical Janardhanan Sreeram; Radhika Srinivasan; Jeyapragasam Meena Devi; Balachandran Unni Nair; Thirumalachari Ramasami

2007-01-01

306

Avian eggshell pigments and their variability  

Microsoft Academic Search

Eggshell pigment constituents were determined by a high-performance liquid chromatography method. Most of the work was done on whole clutches of red-backed shrike (Lanius collurio). In addition to the known pigments (protoporphyrin IX, biliverdin), a new pigment, zinc-containing protoporphyrin IX, was found as well. Its content was highly variable—from 0% to 100%. The content of total protoporphyrin IX (with and

I. Mikšík; V. Holá?; Z. Deyl

1996-01-01

307

Resolution of macular edema in idiopathic juxtafoveal telangiectasis using PDT.  

PubMed

A 57-year-old woman was treated by photodynamic therapy for macular edema due to idiopathic juxtafoveal telangiectasis (presumed type 1A) without subretinal neovascularization. Initial visual acuity of the treated eye was 20/200 and it improved to 20/40 by 3 months after the photodynamic therapy session. Visual acuity remained stable 32 months after the treatment. Color photographs and fundus fluorescein angiography before and after photodynamic therapy revealed regression of hemorrhages, exudates, and fluorescein leakage. Photodynamic therapy has long-term benefits for the patient with idiopathic juxtafoveal telangiectasis, presumed type 1A, because it can improve visual acuity and macular edema. PMID:19205501

Kotoula, Maria G; Chatzoulis, Dimitrios Z; Karabatsas, Constantinos H; Tsiloulis, Aristoteles; Tsironi, Evangelia E

2009-01-01

308

Reappraisal of Spontaneous Closure Rate of Idiopathic Full-Thickness Macular Holes  

PubMed Central

We retrospectively reviewed the records of 142 eyes of 138 patients with idiopathic full-thickness macular hole. Spontaneous closure of idiopathic full-thickness macular hole was observed in five eyes (3.5%) of four patients before the planned vitrectomy. In the era when surgical treatment was not available for macular hole, the rate of spontaneous closure of idiopathic full-thickness macular hole was reported as 6.2%. Among several case reports on spontaneous closure of idiopathic full-thickness macular hole based on the optical coherence tomography images only one study reported the rate of spontaneous closure as 2.7%. According to the previous reports and our results, small idiopathic full-thickness macular holes may close spontaneously in a few percent of all macular hole cases. The rate of spontaneous closure may be affected by the waiting time before vitrectomy. PMID:22934124

Sugiyama, Atsushi; Imasawa, Mitsuhiro; Chiba, Tatsuya; Iijima, Hiroyuki

2012-01-01

309

Volcano like pattern in optical coherence tomography in chronic diabetic macular edema.  

PubMed

In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers. This particular morphological feature at the vitreo-foveolar interface, which we name as "volcano sign", has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event. PMID:24843311

Pai, Sivakami A; Hussain, Nazimul; Hebri, Sudhira P; Lootah, Afra M; Dekhain, Moza A

2014-04-01

310

Non-photosynthetic pigments as potential biosignatures  

NASA Astrophysics Data System (ADS)

Photosynthetic organisms on Earth produce potentially detectable surface reflectance biosignatures due in part to the spectral location and strength of pigment absorption. However, life on Earth uses pigments for a multitude of purposes other than photosynthesis, including coping with extreme environments. Macroscopic environments exist on Earth where the surface reflectance is significantly altered by a nonphotosynthetic pigment, such as the case of hypersaline lakes and ponds (Oren et al. 1992). Here we explore the nature and potential detectability of non-photosynthetic pigments in disk-averaged planetary observations using a combination of laboratory measurements and archival reflectance spectra, along with simulated broadband photometry and spectra. The in vivo visible reflectance spectra of a cross section of pigmented microorganisms are presented to illustrate the spectral diversity of biologically produced pigments. Synthetic broadband colors are generated to show a significant spread in color space. A 1D radiative transfer model (Meadows & Crisp 1996; Crisp 1997) is used to approximate the spectra of scenarios where pigmented organisms are widespread on planets with Earth-like atmospheres. Broadband colors are revisited to show that colors due to surface reflectivity are not robust to the addition of scattering and absorption effects from the atmosphere. We consider a èbest case' plausible scenario for the detection of nonphotosynthetic pigments by using the Virtual Planetary Laboratory's 3D spectral Earth model (Robinson et al. 2011) to explore the detectability of the surface biosignature produced by pigmented halophiles that are widespread on an Earth-analog planet.

Schwieterman, E. W.; Cockell, C. S.; Meadows, V. S.

2014-03-01

311

Pathology Case Study: Pigmented Lesion  

NSDL National Science Digital Library

This is a case study presented by the University of Pittsburgh Department of Pathology in which a 69-year-old man has a pigmented lesion on his right ear. Visitors are given the patient history and microscopic description, including images, and are given the opportunity to diagnose the patient. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose disease. It is also a helpful site for educators to use to introduce or test student learning in dermatologic pathology.

Ejadi, Samuel

2007-09-12

312

Retinitis pigmentosa and macular degeneration in a patient with ataxia with isolated vitamin E deficiency with a novel c.717 del C mutation in the TTPA gene.  

PubMed

Ataxia with isolated vitamin E deficiency (AVED) is a neurodegenerative disease caused by a mutation in the ?-tocopherol transfer protein gene (TTPA). The clinical features of the disease resemble Friedreich's ataxia. However, AVED is associated with low plasma vitamin E levels, which results in compromised antioxidant function. Dysregulation of this lipid-soluble antioxidant vitamin plays a major role in the neurodegeneration observed in AVED. Some AVED patients experience decreased visual acuity. Retinitis pigmentosa is thought to be the main cause of this visual impairment. Although antioxidant levels are important for the prevention of macular degeneration, there have been no reports of macular degeneration in AVED. Here, we describe a patient with AVED with progressive macular degeneration, who carried a novel truncating mutation-c.717 del C (p.D239EfsX25)-in exon 5 of the TTPA gene. These findings suggest that this newly identified mutation results in severely low serum vitamin E levels, which may be associated with the development of retinitis pigmentosa and macular degeneration. PMID:25066259

Iwasa, Kazuo; Shima, Keisuke; Komai, Kiyonobu; Nishida, Yoichiro; Yokota, Takanori; Yamada, Masahito

2014-10-15

313

Comparison of Modified-ETDRS and Mild Macular Grid Laser Photocoagulation Strategies for Diabetic Macular Edema  

PubMed Central

Purpose To compare two laser photocoagulation techniques for treatment of diabetic macular edema (DME): modified-ETDRS direct/grid photocoagulation (mETDRS) and a, potentially milder, but potentially more extensive, mild macular grid (MMG) laser technique in which small mild burns are placed throughout the macula, whether or not edema is present, and microaneurysms are not treated directly. Methods 263 subjects (mean age 59 years) with previously untreated DME were randomly assigned to receive laser photocoagulation by mETDRS (N=162 eyes) or MMG (N=161 eyes) technique. Visual acuity, fundus photographs and OCT measurements were obtained at baseline and after 3.5, 8, and 12 months. Treatment was repeated if DME persisted. Main Outcome Measure Change in OCT measures at 12-months follow up. Results From baseline to 12 months, among eyes with baseline central subfield thickness ? 250 microns, central subfield thickening decreased by an average of 88 microns in the mETDRS group and decreased by 49 microns in the MMG group (adjusted mean difference: 33 microns, 95% confidence interval 5 to 61 microns, P=0.02). Weighted inner zone thickening by OCT decreased by 42 and 28 microns, respectively (adjusted mean difference: 14 microns, 95% confidence interval 1 to 27 microns, P=0.04), maximum retinal thickening (maximum of the central and four inner subfields) decreased by 66 and 39 microns, respectively (adjusted mean difference: 27 microns, 95% confidence interval 6 to 47 microns, P=0.01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference: 0.3 mm3, 95% confidence interval 0.02 to 0.53 mm3, P=0.03). At 12 months, the mean change in visual acuity was 0 letters in the mETDRS group and 2 letters worse in the MMG group (adjusted mean difference: 2 letters, 95% confidence interval ?0.5 to 5 letters, P=0.10). Conclusions At 12 months after treatment, the MMG technique is less effective at reducing OCT measured retinal thickening than the more extensively evaluated current mETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice Modified ETDRS focal photocoagulation should continue as a standard approach for treating diabetic macular edema. PMID:17420366

2008-01-01

314

Anti-vascular endothelial growth factor therapy for diabetic macular edema  

PubMed Central

Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients. PMID:24324855

Hopkins, J. Jill; Sorof, Jonathan; Ehrlich, Jason S.

2013-01-01

315

Variability of surface pigment concentrations in the South Atlantic Bight  

NASA Technical Reports Server (NTRS)

A time sequence of surface pigment images of the South Atlantic Bight (SAB), derived from the Nimbus 7 CZCS for the period between November 1978 and October 1979, was correlated with in situ observations of hydrographic parameters, fresh-water discharge, sea level, coastal winds, and currents in order to couple physical processes and the spatial and temporal variability of the surface pigment fields. A definite seasonal modulation of the surface pigment fields was found, with the concentrations in the Georgia Bight being highest in summer, and those north of Cape Romain highest in winter. This phase difference was found to be the result of variations in wind fields, Gulf Stream-shelf interactions, and fresh-water discharge patterns. At some locations (e.g., near Charleston) the alongshore band of high pigment concentrations increased in width throughout the year; at other locations (near Jacksonville), the alongsore band exhibited a minimum width in the summer and a maximum width in the fall of 1979.

Mcclain, Charles R.; Yoder, James A.; Blanton, J. O.; Atkinson, L. P.; Lee, T. N.

1988-01-01

316

Continental variation in wing pigmentation in Calopteryx damselflies is related to the presence of heterospecifics.  

PubMed

Wing pigmentation in Calopteryx damselflies, caused by the deposition of melanin, is energetically expensive to produce and enhances predation risk. However, patterns of melanisation are used in species identification, greater pigmentation is an accurate signal of male immune function in at least some species, and there may be a role for pigment in thermoregulation. This study tested two potential hypotheses to explain the presence of, and variation in, this pigmentation based on these three potential benefits using 907 male specimens of Calopteryx maculata collected from 49 sites (34 discrete populations) across the geographical range of the species in North America: (i) pigmentation varies with the presence of the closely related species, Calopteryx aequabilis, and (ii) pigment increases at higher latitudes as would be expected if it enhances thermoregulatory capacity. No gradual latitudinal pattern was observed, as might be expected if pigmentation was involved in thermoregulation. However, strong variation was observed between populations that were sympatric or allopatric with C. aequabilis. This variation was characterised by dark wings through allopatry in the south of the range and then a step change to much lighter wings at the southern border of sympatry. Pigmentation then increased further north into the sympatric zone, finally returning to allopatry levels at the northern range margin. These patterns are qualitatively similar to variation in pigmentation in C. aequabilis, meaning that the data are consistent with what would be expected from convergent character displacement. Overall, the results corroborate recent research that has suggested sexual selection as a primary driver behind the evolution of wing pigmentation in this group. PMID:24949250

Hassall, Christopher

2014-01-01

317

Natural selection along an environmental gradient: a classic cline in mouse pigmentation.  

PubMed

We revisited a classic study of morphological variation in the oldfield mouse (Peromyscus polionotus) to estimate the strength of selection acting on pigmentation patterns and to identify the underlying genes. We measured 215 specimens collected by Francis Sumner in the 1920s from eight populations across a 155-km, environmentally variable transect from the white sands of Florida's Gulf coast to the dark, loamy soil of southeastern Alabama. Like Sumner, we found significant variation among populations: mice inhabiting coastal sand dunes had larger feet, longer tails, and lighter pigmentation than inland populations. Most striking, all seven pigmentation traits examined showed a sharp decrease in reflectance about 55 km from the coast, with most of the phenotypic change occurring over less than 10 km. The largest change in soil reflectance occurred just south of this break in pigmentation. Geographic analysis of microsatellite markers shows little interpopulation differentiation, so the abrupt change in pigmentation is not associated with recent secondary contact or reduced gene flow between adjacent populations. Using these genetic data, we estimated that the strength of selection needed to maintain the observed distribution of pigment traits ranged from 0.0004 to 21%, depending on the trait and model used. We also examined changes in allele frequency of SNPs in two pigmentation genes, Mc1r and Agouti, and show that mutations in the cis-regulatory region of Agouti may contribute to this cline in pigmentation. The concordance between environmental variation and pigmentation in the face of high levels of interpopulation gene flow strongly implies that natural selection is maintaining a steep cline in pigmentation and the genes underlying it. PMID:18489719

Mullen, Lynne M; Hoekstra, Hopi E

2008-07-01

318

Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism  

PubMed Central

Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin. We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice homozygous for either the Tyrc-2J null allele or the Tyrc-h allele, which model OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyrc-h/c-h mice manifested increased pigmentation in their fur and irides and had more pigmented melanosomes. High levels of tyrosine improved the stability and enzymatic function of the Tyrc-h protein and also increased overall melanin levels in melanocytes from a human with OCA-1B. These results suggest that the use of nitisinone in OCA-1B patients could improve their pigmentation and potentially ameliorate vision loss. PMID:21968110

Onojafe, Ighovie F.; Adams, David R.; Simeonov, Dimitre R.; Zhang, Jun; Chan, Chi-Chao; Bernardini, Isa M.; Sergeev, Yuri V.; Dolinska, Monika B.; Alur, Ramakrishna P.; Brilliant, Murray H.; Gahl, William A.; Brooks, Brian P.

2011-01-01

319

Pigmented squamous intraepithelial neoplasia of the esophagus  

PubMed Central

Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few reports have documented invasive SCC or SCC in situ (intraepithelial neoplasia, IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC, in some organs. However, case series of pigmented SCC or IEN of the esophagus have not yet been reported. This is the first study to analyze the incidence and clinicopathological features of pigmented SCC or IEN of the esophagus. We reviewed 18 surgically-resected and 122 endoscopically-resected esophageal specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed in this series, and all of them were located in the middle to lower third of the esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous epithelium around the IEN. The incidence of pigmented IEN was 2.5% of all endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive SCC was detected in both endoscopically-resected and surgically-resected specimens. The mechanism of pigmentation of esophageal IEN is unknown. However, production of melanocyte chemotactic factors by tumor cells has been demonstrated in pigmented SCC of the oral mucosa. Moreover, two of 3 cases of pigmented IEN in the present series had melanocytosis in the non-neoplastic squamous epithelium, and melanocytosis is thought to be associated with chronic esophagitis, therefore, it has been hypothesized that various stimuli can cause pigmentation in squamous epithelium. Additional studies are needed to clarify the mechanism of pigmentation in squamous IEN of the esophagus. PMID:24040452

Ishida, Mitsuaki; Mochizuki, Yosuke; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

2013-01-01

320

Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema  

PubMed Central

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

Fong, Angie HC; Lai, Timothy YY

2013-01-01

321

Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema.  

PubMed

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

Fong, Angie H C; Lai, Timothy Y Y

2013-01-01

322

Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema  

PubMed Central

The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme (APE) in the management of diabetic retinopathy and diabetic macular edema (DME). Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included. All cases were treated with an initial intravitreal injection of APE and reevaluated one month later, measuring changes in best-corrected visual acuity (BCVA), macular thickness and the status of the posterior hyaloid. A second APE injection was performed in cases with no evident posterior vitreous detachment (PVD) after the initial treatment. Sixty-three eyes were included in the present review. A complete PVD appeared in 38% of cases (24 eyes) after one injection of plasmin and the total increased to 51% (32 eyes) after the second injection, separated at least by one month. The central macular thickness improved in all cases (100%) and BCVA in 89%. Finally, in 50% of eyes with proliferative diabetic retinopathy, a high reduction of new vessels regression was observed. Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema. PMID:24379923

Diaz-Llopis, Manuel; Udaondo, Patricia; Millan, Jose Maria; Arevalo, J Fernando

2013-01-01

323

Spectrum of ABCR gene mutations in autosomal recessive macular dystrophies  

Microsoft Academic Search

Stargardt disease (STGD) and late-onset fundus flavimaculatus (FFM) are autosomal recessive conditions leading to macular degenerations in childhood and adulthood, respectively. Recently, mutations of the photoreceptor cell-specific ATP binding transporter gene (ABCR) have been reported in Stargardt disease. Here, we report on the screening of the whole coding sequence of the ABCR gene in 40 unrelated STGD and 15 FFM

Jean-Michel Rozet; Sylvie Gerber; Eric Souied; Isabelle Perrault; Sophie Châtelin; Imad Ghazi; Corinne Leowski; Jean-Louis Dufier; Arnold Munnich; Josseline Kaplan; J-M Rozet

1998-01-01

324

Complement factor d in age-related macular degeneration  

Microsoft Academic Search

Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was

C. M. Stanton; J. R. W. Yates; A. I. den Hollander; J. M. Seddon; A. Swaroop; D. Stambolian; S. Fauser; C. B. Hoyng; Y. Yu; K. Atsuhiro; K. Branham; M. Othman; W. Chen; E. Kortvely; K. Chalmers; C. Hayward; A. T. Moore; B. Dhillon; M. Ueffing; A. F. Wright

2011-01-01

325

Inflammation in Dry Age-Related Macular Degeneration  

Microsoft Academic Search

Purpose: To summarize the current information regarding the role of immune and inflammatory response in the pathogenesis of dry age-related macular degeneration (ARMD). Methods: A Pubmed search was conducted of the period January 1999 to 2005. Relevant information in the literature on the role of inflammation in early dry ARMD was reviewed. Results: Some important evidence for inflammation in early

Eduardo B. Rodrigues

2007-01-01

326

Age-related macular degeneration among the Inuit in Greenland  

Microsoft Academic Search

Objectives. To investigate the clinical appearance and prevalence of Age-related Macular Degeneration (AMD) among the Inuit in Greenland, to investigate risk factors and to initiate the search for possible genetic markers. Study design. A cross-sectional population study including all individuals older than 60 years of age, born in Greenland and living in the communities of Nuuk and Sisimiut, was performed

Nis Andersen

2003-01-01

327

Regression of diabetic macular edema after subcutaneous exenatide.  

PubMed

The aim of this study is to report a case of complete regression of diabetic macular edema after subcutaneous injection of exenatide in a patient with type 2 diabetes mellitus. This study is an interventional case report. Blood investigations, complete ophthalmic examinations and optical coherence tomography were performed. A 55-year-old female affected by poorly controlled type 2 diabetes mellitus presented with visual impairment due to macular edema in the right eye. The left eye showed mild edema without visual loss. Best-corrected visual acuity (BCVA) was 20/80 and 20/20, respectively. The patient was encouraged to improve metabolic control, and the antidiabetic therapy was modified combining exenatide 10 ?g subcutaneously twice daily to her regimen of oral metformin. The patient did not receive any ocular treatment. A complete tomographic resolution of macular edema was observed after 1 month and BCVA improved to 20/63. These findings were confirmed for the entire 6-month follow-up duration. No ocular or non-ocular adverse events were recorded. This is the first reported case of complete regression of macular edema in a diabetic patient after subcutaneous injection of exenatide. PMID:23925692

Sarao, Valentina; Veritti, Daniele; Lanzetta, Paolo

2014-06-01

328

Thoracic trident pigmentation in Drosophila melanogaster : Differentiation of geographical populations  

E-print Network

Thoracic trident pigmentation in Drosophila melanogaster : Differentiation of geographical : Drosophila melanogaster, pigmentation, teuzperature response, maternal effect, latitudinal cline. Résumé La pigmentation thoracique en forme de trident chez Drosophila melanogaster : différenciation de populations de

Paris-Sud XI, Université de

329

Hyperspectral remote sensing of plant pigments  

Microsoft Academic Search

The dynamics of pigment concentrations are diagnostic of a range of plant physiological properties and pro- cesses. This paper appraises the developing technolo- gies and analytical methods for quantifying pigments non-destructively and repeatedly across a range of spatial scales using hyperspectral remote sensing. Progress in deriving predictive relationships between various characteristics and transforms of hyperspectral reflectance data are evaluated and

George Alan Blackburn

2010-01-01

330

Nanoscale porosity in pigments for chemical sensing  

NASA Astrophysics Data System (ADS)

Porous pigments in which chemically responsive dyes have been immobilized in a matrix of organically modified siloxanes (ormosils) have been prepared and characterized by AFM, TEM, EDS, and optical analysis. In typical chemical sensing applications, an array of 36 different porous ormosil pigments are deposited on polyethylene terephthalate (PET) film.

Kemling, Jonathan W.; Suslick, Kenneth S.

2011-05-01

331

Angiotensin II-Induced Hypertension Regulates AT1 Receptor Subtypes and Extracellular Matrix Turnover in Mouse Retinal Pigment Epithelium  

PubMed Central

Accumulation of specific deposits and extracellular molecules under the retinal pigment epithelium (RPE) have been previously observed in eyes with age-related macular degeneration (AMD) and may play a role in the pathogenesis of AMD. Even though age is the major determinant for developing AMD, clinical studies have revealed hypertension (HTN) as another systemic risk factor. Angiotensin II (Ang II) is considered the most important hormone associated with HTN. To evaluate the relationship of Ang II to AMD, we studied whether mouse RPE expresses functional Ang II receptor subtypes and whether HTN-induced Ang II regulates expression of these receptors as well as critical ECM molecules (MMP-2 and type IV collagen) involved in ECM turnover in RPE. We used 9 month-old C57BL/6 male mice infused with Ang II alone or Ang II in combination with the AT1 receptor antagonist candesartan or the AT2 receptor antagonist PD123319 for 4 weeks to determine whether HTN-associated Ang II was important for ECM regulation in RPE. We found that mouse RPE expressed both Ang II receptor subtypes at the mRNA and protein levels. Infusion with Ang II induced HTN and elevated plasma and ocular Ang II levels. Ang II also regulated AT1a and AT1b receptor mRNA expression, the intracellular concentration of calcium [Ca2+]i, MMP-2 activity, and type IV collagen accumulation. Concurrent administration of Ang II with the AT1 receptor blocker prevented the increase in blood pressure and rise in ocular Ang II levels, as well as the calcium and MMP-2 responses. In contrast, the type IV collagen response to Ang II was prevented by blockade of AT2 receptors, but not AT1 receptors. Plasma Ang II levels were not modified by the AT1 or AT2 receptor blockade. Since the effects of Ang II on MMP-2 and type IV collagen require inhibition of both Ang II receptor subtypes, these receptors may play a role as a potential therapeutic targets to prevent ECM turnover dysregulation in the RPE basement membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD. PMID:19281810

Praddaude, Francoise; Cousins, Scott W.; Pecher, Christiane; Marin-Castano, Maria E.

2009-01-01

332

Quantitative analysis of macular contraction in idiopathic epiretinal membrane  

PubMed Central

Background We aimed to quantify the displacement of macular capillaries using infrared fundus photographs and image processing software (ImageJ) in patients with idiopathic epiretinal membrane (ERM) who have undergone vitrectomy and to analyze the correlation between vessel displacement and retinal thickness. Methods This prospective study included 16 patients who underwent vitrectomy for idiopathic ERM. Ophthalmic examination and optical coherence tomography (OCT) were performed before and 3 months after surgery. The length of radial vessel segment included in each area (VLA) and the length from the foveola to the vessel branching point (FBL) depending on the superior, inferior, nasal, and temporal areas of the macula were measured using infrared fundus images and image processing software (ImageJ). Preoperative and postoperative parameters were compared and correlations between VLA, FBL, macular thickness, and visual acuity were assessed. Results The VLA of superior, inferior, and temporal areas showed a significant postoperative reduction. VLA differences showed a positive correlation with differences in macular thickness, which corresponded to the superior, inferior, and temporal areas; however, no correlation was observed in the nasal area. The FBL of the superior and inferior areas was significantly increased postoperatively. A positive correlation was observed between FBL differences and macular thickness differences in the superior area. Postoperative change in VLA and FBL did not show a significant correlation with postoperative best corrected visual acuity (BCVA) and BCVA differences. Conclusions Infrared fundus photographs and image processing software can be useful for quantifying progressive changes in retinal surface distortion after surgical removal of ERM. Macular edema and vascular distortion showed significant improvement after surgery. Furthermore, a correlation was observed between topographic and tomographic changes. PMID:24735324

2014-01-01

333

Cost-Effectiveness of Bevacizumab and Ranibizumab for Newly Diagnosed Neovascular Macular Degeneration (An American Ophthalmological Society Thesis)  

PubMed Central

Purpose: To determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections. Methods: Using a Markov model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), the Medicare Fee Schedules, and the medical literature. Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242,357 per quality-adjusted life year (QALY). Monthly ranibizumab gains an additional 0.02 QALYs vs monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million per QALY. As-needed ranibizumab was dominated by monthly bevacizumab. In sensitivity analyses assuming a willingness to pay of $100,000 per QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100,000 per QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by one category (eg, from 20/25–20/40 to 20/50–20/80) after 2 years but all patients receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340 per QALY. Conclusion: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration. PMID:24167325

Stein, Joshua D.; Newman-Casey, Paula Anne; Mrinalini, Tavag; Lee, Paul P.; Hutton, David W.

2013-01-01

334

IVTA as Adjunctive Treatment to PRP and MPC for PDR and Macular Edema: A Meta-Analysis  

PubMed Central

Background To quantify the effect of a combination treatment of intravitreal triamcinolone acetonide (IVTA) injection, panretinal photocoagulation (PRP), and macular photocoagulation (MPC) in patients with proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Methodology/Principal Findings We conducted a meta-analysis and searched for reports concerning IVTA injection combined with PRP for the treatment of PDR and DME using Medline, EMbase, Web of Science, the Cochrane Library, and Google according to Cochrane evaluation guidelines. The quality of the reports was evaluated using the Jadad score. Only four studies were ultimately included in this meta-analysis and the fixed-effects model was used. Treatment with IVTA injection combined with PRP and MPC significantly improved BCVA (p<0.001) from one to six months, compared with PRP and MPC alone. There was a statistically significant mean difference in central macular thickness (CMT), at the one-month follow-up (p<0.001). No evidence of publication bias was present. There was a low level of heterogeneity in this group of studies. Conclusions/Significance This meta-analysis indicates that IVTA injection combined with PRP and MPC results in an improvement of BCVA, and CMT reduction in patients with PDR and DME. PMID:22973465

Liu, Lei; Wu, Xiaomei; Geng, Jin; Yuan, Zhe; Chen, Lei

2012-01-01

335

Anthocyanins. Plant pigments and beyond.  

PubMed

Anthocyanins are plant pigments widespread in nature. They play relevant roles in plant propagation and ecophysiology and plant defense mechanisms and are responsible for the color of fruits and vegetables. A large number of novel anthocyanin structures have been identified, including new families such as pyranoanthocyanins or anthocyanin oligomers; their biosynthesis pathways have been elucidated, and new plants with "a la carte" colors have been created by genetic engineering. Furthermore, evidence about their benefits in human health has accumulated, and processes of anthocyanin absorption and biotransformation in the human organism have started to be ascertained. These advances in anthocyanin research were revised in the Seventh International Workshop on Anthocyanins that took place in Porto (Portugal) on September 9-11, 2013. Some selected papers are collected in this special issue, where aspects such as anthocyanin accumulation in plants, relationship with color expression, stability in plants and food, and bioavailability or biological activity are revised. PMID:24970106

Santos-Buelga, Celestino; Mateus, Nuno; De Freitas, Victor

2014-07-23

336

Structure of plant bile pigments  

SciTech Connect

Selective peptide cleavage has provided a general procedure for the study of the structure, including stereochemistry, of plant bile pigments. The information derived from the synthesis and spectral analysis of a series of 2,3-dihydrodioxobilins allows the determination of the trans relative stereochemistry for ring A of the ..beta../sub 1/-phycocyanobilin from C-phycocyanin as well as for ring A of phytochrome. A complete structure proof of the five phycoerythrobilins attached to the ..cap alpha.. and ..beta.. subunits of B-phycoerythrin is described. One of these tetrapyrroles is doubly-peptide linked to a single peptide chain through two thioethers at the C-3' and C-18' positions. The four remaining phycoerythrobilins are singly-linked to the protein through thioethers at the C-3' position and all possess the probable stereochemistry C-2(R), C-3(R), C-3'(R), and C-16(R).

Schoenleber, R.W.

1983-12-01

337

Molecular and developmental contributions to divergent pigment patterns in marine and freshwater sticklebacks  

PubMed Central

SUMMARY Pigment pattern variation across species or populations offers a tractable framework in which to investigate the evolution of development. Juvenile threespine sticklebacks (Gasterosteus aculeatus) from marine and freshwater environments exhibit divergent pigment patterns that are associated with ecological differences. Juvenile marine sticklebacks have a silvery appearance, whereas sticklebacks from freshwater environments exhibit a pattern of vertical bars. We investigated both the developmental and molecular basis of this population-level variation in pigment pattern. Time course imaging during the transition from larval to juvenile stages revealed differences between marine and freshwater fish in spatial patterns of chromatophore differentiation as well as in pigment amount and dispersal. In freshwater fish, melanophores appear primarily within dark bars whereas iridophores appear within light bars. By contrast, in marine fish, these chromatophores are interspersed across the flank. In addition to spatially segregated chromatophore differentiation, pigment amount and dispersal within melanophores varies spatially across the flank of freshwater, but not marine fish. To gain insight into the molecular pathways that underlie the differences in pigment pattern development, we evaluated differential gene expression in the flanks of developing fish using high throughput cDNA sequencing (RNA-seq) and quantitative PCR. We identified several genes that were differentially expressed across dark and light bars of freshwater fish, and between freshwater and marine fish. Together, these experiments begin to shed light on the process of pigment pattern evolution in sticklebacks. PMID:22765206

Greenwood, Anna K.; Cech, Jennifer N.; Peichel, Catherine L.

2012-01-01

338

Pigments, Parasites and Personalitiy: Towards a Unifying Role for Steroid Hormones?  

PubMed Central

A surging interest in the evolution of consistent trait correlations has inspired research on pigment patterns as a correlate of behavioural syndromes, or “animal personalities”. Associations between pigmentation, physiology and health status are less investigated as potentially conserved trait clusters. In the current study, lice counts performed on farmed Atlantic salmon Salmo salar naturally infected with ectoparasitic sea lice Lepeophtheirus salmonis showed that individual fish with high incidence of black melanin-based skin spots harboured fewer female sea lice carrying egg sacs, compared to less pigmented fish. There was no significant association between pigmentation and lice at other developmental stages, suggesting that host factors associated with melanin-based pigmentation may modify ectoparasite development to a larger degree than settlement. In a subsequent laboratory experiment a strong negative correlation between skin spots and post-stress cortisol levels was revealed, with less pigmented individuals showing a more pronounced cortisol response to acute stress. The observation that lice prevalence was strongly increased on a fraction of sexually mature male salmon which occurred among the farmed fish further supports a role for steroid hormones as mediators of reduced parasite resistance. The data presented here propose steroid hormones as a proximate cause for the association between melanin-based pigmentation and parasites. Possible fundamental and applied implications are discussed. PMID:22493685

Kittilsen, Silje; Johansen, Ida Beitnes; Braastad, Bjarne Olai; ?verli, ?yvind

2012-01-01

339

A non-linear irreversible thermodynamic perspective on organic pigment proliferation and biological evolution  

NASA Astrophysics Data System (ADS)

The most important thermodynamic work performed by life today is the dissipation of the solar photon flux into heat through organic pigments in water. From this thermodynamic perspective, biological evolution is thus just the dispersal of organic pigments and water throughout Earth's surface, while adjusting the gases of Earth's atmosphere to allow the most intense part of the solar spectrum to penetrate the atmosphere and reach the surface to be intercepted by these pigments. The covalent bonding of atoms in organic pigments provides excited levels compatible with the energies of these photons. Internal conversion through vibrational relaxation to the ground state of these excited molecules when in water leads to rapid dissipation of the solar photons into heat, and this is the major source of entropy production on Earth. A non-linear irreversible thermodynamic analysis shows that the proliferation of organic pigments on Earth is a direct consequence of the pigments catalytic properties in dissipating the solar photon flux. A small part of the energy of the photon goes into the production of more organic pigments and supporting biomass, while most of the energy is dissipated and channeled into the hydrological cycle through the latent heat of vaporization of surface water. By dissipating the surface to atmosphere temperature gradient, the hydrological cycle further increases the entropy production of Earth. This thermodynamic perspective of solar photon dissipation by life has implications to the possibility of finding extra-terrestrial life in our solar system and the Universe.

Michaelian, K.

2013-12-01

340

Deciphering mutant ELOVL4 activity in autosomal-dominant Stargardt macular dystrophy.  

PubMed

Autosomal-dominant Stargardt-like macular dystrophy [Stargardt3 (STGD3)] results from single allelic mutations in the elongation of very-long-chain fatty acids-like 4 (ELOVL4), whereas recessive mutations lead to skin and brain dysfunction. ELOVL4 protein localizes to the endoplasmic reticulum, where it mediates the condensation reaction catalyzing the formation of very-long-chain (VLC) (C-28 to C-40) fatty acids, saturated and polyunsaturated (PUFA). The defective gene product is truncated at the C terminus, leading to mislocalization and aggregation in other organelles. We hypothesized that the STGD3 truncated mutant may generate mislocalized, and therefore toxic, keto intermediates of fatty acid elongation, thereby contributing to the disease process. Using cell-based and cell-free microsome assays, we found that the truncated protein lacked innate condensation activity. Coexpression of different forms of wild-type and mutant ELOVL4 revealed a large dominant-negative effect of mutant protein on ELOVL4 localization and enzymatic activity, resulting in reduced VLC-PUFA synthesis. The reduction in VLC-PUFA levels in STGD3 and age-related macular degeneration may be a contributing factor to their retinal pathology. PMID:23509295

Logan, Sreemathi; Agbaga, Martin-Paul; Chan, Michael D; Kabir, Nabila; Mandal, Nawajes A; Brush, Richard S; Anderson, Robert E

2013-04-01

341

Diabetic macular edema: new concepts in patho-physiology and treatment  

PubMed Central

Diabetic macular edema (DME), a serious eye complication caused primarily by hyperglycemia, is one of the major causes of blindness. DME, which is characterized by cystic retinal thickening or lipid deposition, is prone to relapse after successful treatment. DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies. Starling’s law theory explains many of the features of DME. Early detection and treatment of DME can prevent vision loss. Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision. Laser photocoagulation is still the gold standard of treatment for DME which does not involve the central macular. This review outlines these new treatments with particular emphasis on the optimal timing of how they are given. PMID:24955234

2014-01-01

342

Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors  

Microsoft Academic Search

The visual pigments of most invertebrate photoreceptors have two thermostable photo-interconvertible states, the ground state\\u000a rhodopsin and photo-activated metarhodopsin, which triggers the phototransduction cascade until it binds arrestin. The ratio\\u000a of the two states in photoequilibrium is determined by their absorbance spectra and the effective spectral distribution of\\u000a illumination. Calculations indicate that metarhodopsin levels in fly photoreceptors are maintained below

Doekele G. StavengaRoger; Roger C. Hardie

2011-01-01

343

Sequence divergence of the red and green visual pigments in great apes and humans.  

PubMed Central

We have determined the coding sequences of red and green visual pigment genes of the chimpanzee, gorilla, and orangutan. The deduced amino acid sequences of these pigments are highly homologous to the equivalent human pigments. None of the amino acid differences occurred at sites that were previously shown to influence pigment absorption characteristics. Therefore, we predict the spectra of red and green pigments of the apes to have wavelengths of maximum absorption that differ by < 2 nm from the equivalent human pigments and that color vision in these nonhuman primates will be very similar, if not identical, to that in humans. A total of 14 within-species polymorphisms (6 involving silent substitutions) were observed in the coding sequences of the red and green pigment genes of the great apes. Remarkably, the polymorphisms at 6 of these sites had been observed in human populations, suggesting that they predated the evolution of higher primates. Alleles at polymorphic sites were often shared between the red and green pigment genes. The average synonymous rate of divergence of red from green sequences was approximately 1/10th that estimated for other proteins of higher primates, indicating the involvement of gene conversion in generating these polymorphisms. The high degree of homology and juxtaposition of these two genes on the X chromosome has promoted unequal recombination and/or gene conversion that led to sequence homogenization. However, natural selection operated to maintain the degree of separation in peak absorbance between the red and green pigments that resulted in optimal chromatic discrimination. This represents a unique case of molecular coevolution between two homologous genes that functionally interact at the behavioral level. PMID:8041777

Deeb, S S; Jorgensen, A L; Battisti, L; Iwasaki, L; Motulsky, A G

1994-01-01

344

Engineering efficient retinal pigment epithelium differentiation from human pluripotent stem cells.  

PubMed

Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration. Although most hESC lines will produce a number of clusters of pigmented RPE cells within 30-50 days when allowed to spontaneously differentiate, the timing and efficiency of differentiation is highly variable. This could prove problematic in the design of robust processes for the large scale production of RPE cells for cell therapy. In this study we sought to identify, quantify, and reduce the sources of variability in hESC-RPE differentiation. By monitoring the emergence of pigmented cells over time, we show how the cell line, passaging method, passage number, and seeding density have a significant and reproducible effect on the RPE yield. To counter this variability, we describe the production of RPE cells from two cell lines in feeder-free, density controlled conditions using single cell dissociation and seeding that is more amenable to scaled up production. The efficacy of small molecules in directing differentiation toward the RPE lineage was tested in two hESC lines with divergent RPE differentiation capacities. Neural induction by treatment with a bone morphogenetic protein inhibitor, dorsomorphin, significantly enhanced the RPE yield in one cell line but significantly reduce it in another, generating instead a Chx10 positive neural progenitor phenotype. This result underlines the necessity to tailor differentiation protocols to suit the innate properties of different cell lines. PMID:25273541

Lane, Amelia; Philip, Lissa Rachel; Ruban, Ludmila; Fynes, Kate; Smart, Matthew; Carr, Amanda; Mason, Chris; Coffey, Pete

2014-11-01

345

A tattoo pigmented node and breast cancer.  

PubMed

Over the last decade, the axillary SLNB has replaced routine ALND for clinical staging in early breast cancer. Studies describe a potential pitfall in the identification of a true sentinel node during surgery due to lymph node pigmentation secondary to migration of tattoo dye. These pigmented “pseudo-sentinel” nodes, if located superficially in the axilla, may mimic the blue sentinel node on visual inspection, therefore missing the true sentinel node and potentially understaging the patient. Here, we present a case report of a breast cancer patient with a tattoo and discuss the importance of tattoo pigment in the LN (Fig. 1, Ref. 8). PMID:25174062

Soran, A; Kanbour-Shakir, A; Bas, O; Bonaventura, M

2014-01-01

346

Cost-effectiveness of smoking cessation to prevent age-related macular degeneration  

Microsoft Academic Search

BACKGROUND: Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk. METHODS: We fitted a function predicting the decline in risk of macular degeneration after quitting to data from 7 studies involving 1,488 patients. We assessed the cost-effectiveness of smoking cessation in terms of its impact on macular degeneration-related outcomes

Susan F Hurley; Jane P Matthews; Robyn H Guymer

2008-01-01

347

Computer-assisted three-dimensional reconstruction and simulations of vestibular macular neural connectivities  

NASA Technical Reports Server (NTRS)

Results of computer-assisted research concerned with the three-dimensional reconstruction and simulations of vestibular macular neural connectivities are summarized. The discussion focuses on terminal/receptive fields, the question of synapses across the striola, endoplasmic reticulum and its potential role in macular information processing, and the inner epithelial plexus. Also included are preliminary results of computer simulations of nerve fiber collateral functioning, an essential step toward the three-dimensional simulation of a functioning macular neural network.

Ross, Muriel D.; Chimento, Thomas; Doshay, David; Cheng, Rei

1992-01-01

348

Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization  

PubMed Central

The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-?B (NF-?B) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-?B, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE–Bruch?s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. PMID:24624338

Li, Y.; Liu, X.; Zhou, T.; Kelley, M.R.; Edwards, P.; Gao, H.; Qiao, X.

2014-01-01

349

Epigalloccatechin-3-gallate inhibits ocular neovascularization and vascular permeability in human retinal pigment epithelial and human retinal microvascular endothelial cells via suppression of MMP-9 and VEGF activation.  

PubMed

Epigalloccatechin-3-gallate (EGCG) is the main polyphenol component of green tea (leaves of Camellia sinensis). EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a key role in the processes of extracellular matrix (ECM) remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNF-?) in human retinal pigment epithelial cells (HRPECs). EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2) by inhibiting generation of reactive oxygen species (ROS). EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs). Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31) on corneal neovascularization (CNV) induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization. PMID:25123184

Lee, Hak Sung; Jun, Jae-Hyun; Jung, Eun-Ha; Koo, Bon Am; Kim, Yeong Shik

2014-01-01

350

DNA shuffling of cytochromes P450 for indigoid pigment production.  

PubMed

DNA family shuffling is a powerful method of directed evolution applied for the generation of novel enzymes with the aim of improving their existing features or creating completely new enzyme properties. This method of evolution in vitro requires parental sequences containing a high level of sequence similarity, such as is found in family members of cytochrome P450 enzymes. Cytochromes P450 (P450s or CYPs) are capable of catalyzing a variety of chemical reactions and generating a wide range of products including dye production (e.g., pigments indigo and indirubin). Application of the method of DNA family shuffling described here has enabled us to create novel P450 enzymes and to further extend the capacity of P450 to oxidize indole, leading to pigment formation. PMID:23475680

Rosic, Nedeljka N

2013-01-01

351

Formulae for Determination of Chlorophyllous Pigments Extracted with N,N-Dimethylformamide 1  

PubMed Central

The extraction of chlorophylls in higher plant tissue using N,N-dimethylformamide expedites the process and enables the determination of small samples with low pigment level. Absorption spectra of Chl a, Chl b, and Pchl and of their acidified derivatives, the phaeophytins, were recorded. Conversion of Chl b to its corresponding acidified product occurs much more slowly than that of Chl a and Pchl. When acidified, Pchl differs from Chl a and Chl b by the disappearance of the red band in the absorption spectrum. Specific extinction coefficients were determined and formulae for quantitative determination of pigments concentrations were developed. When concentrations of pigments are low, as in etiolated plant material, the absorption spectra of the chlorophylls can be distorted due to the presence of other substances simultaneously extracted; formulae for pigment determination under such circumstances were also derived. PMID:16662407

Moran, Rami

1982-01-01

352

Conservation of the chromatophore pigment response.  

PubMed

Toxicant sensing technology has evolved to include biological sensors, such as cell-based biosensors, which rely on viable cells to convey a measurable physiological signal. Chromatophores are a class of pigment cells that have been investigated as cell-based biosensors. We report the characterization of Oncorhynchus tshawytscha melanophores and describe the melanophore pigment response to neurotransmitters in terms of pigment area occupied. Compared with the previously described model, Betta splendens erythrophores, O. tshawytscha melanophores responded similarly, indicating that pigment responses are biologically conserved between these two species. Additionally, melanophores responded to mercuric chloride and sodium arsenite, similar to B. splendens erythrophores, suggesting that melanophores can be used as detectors for environmental toxicants. This report highlights the potential of O. tshawytscha melanophores to be used as cell-based biosensors to address environmental toxicity, and warrants a continued investigation to strengthen this technology and its applications. PMID:20809546

Dukovcic, Stephanie R; Hutchison, Janine R; Trempy, Janine E

2010-08-01

353

Dynamics of pigmentation induction by repeated UV exposures: dose, dose interval and UV spectrum dependence  

PubMed Central

Summary Background The dynamics of UV-induced melanogenesis have been well-characterized for single UV exposures. However, our knowledge of the effects of repeated UV exposures on the development of new pigmentation is limited. Objectives To characterize the dynamics and dose dependence of pigmentation induction by repeated UV exposures using two different UV sources. Methods A total of 40 healthy subjects participated in the study; 21 were exposed to a 5% UVB/95% UVA source and 19 were exposed to a 2% UVB/98% UVA source. Skin phototypes 2 to 3 were represented. Subjects were exposed 1-3 times per week. The minimal erythemal dose and minimal melanogenic dose of all subjects were determined, and both visual and instrumental observations of the development of pigmentation and erythema were recorded. Results Dark brown pigmentation could be produced by a cumulative UV dose of 4200 J/m2 given as 10 exposures over 5 weeks. However, comparable pigmentation could also be induced by a cumulative dose of 2900 J/m2 given in 8 exposures over 4 weeks. The lowest cumulative dose of 1900 J/m2 given over 4 weeks produced moderate pigmentation. The 2% UVB source led to earlier and darker pigmentation than the 5% UVB source did for equally erythemogenic doses. Conclusions These observations show that the dynamics of melanogenesis induced by repeated exposures depends on UV dose, dose interval and emission spectrum. They also indicate that increasing the UV dose above a certain level of cumulative exposure does not significantly increase the level of UV-induced pigmentation. PMID:18616777

Miller, S. A.; Coelho, S. G.; Zmudzka, B. Z.; Bushar, H. F.; Yamaguchi, Y.; Hearing, V. J.; Beer, J. Z.

2009-01-01

354

Use of nepafenac (Nevanac®) in combination with intravitreal anti-VEGF agents in the treatment of recalcitrant exudative macular degeneration requiring monthly injections  

PubMed Central

Purpose The purpose of this study is to determine the efficacy of combining topical nepafenac with monthly intravitreal injections of ranibizumab or bevacizumab in the treatment of recalcitrant exudative macular degeneration. Methods This was a retrospective, consecutive case series of patients with exudative macular degeneration requiring maintenance therapy of antivascular endothelial growth factor ( anti-VEGF) injections at least every 6 weeks, who were started on topical nepafenac. Despite frequent anti-VEGF dosing, all patients included in the study had persistence of any combination of the following: intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Patients underwent pinhole visual acuity, clinical exam, and optical coherence tomography (OCT) at baseline and every follow-up visit. Response to therapy was graded by reviewing quantitative and qualitative OCT data, and statistical analysis was done with paired Student’s t-test. Results Twenty-five patients (average age 77; 14 male and 11 female) were reviewed; the mean number of previous injections was 17.4 (range 3–31). Baseline mean visual acuity was 20/55, and final mean visual acuity after 3 months of treatment was 20/51 (P = 0.13). Monthly mean central foveal thickness measurements were 248, 250, 257, and 247 ?m (P = 0.53) at baseline, 1, 2, and 3 months, respectively. By the end of the 3-month time point, qualitative OCT findings on 13 patients treated with nepafenac were classified as stable, 10 as better, and 2 as worse. Conclusions There was no significant change in visual acuity or quantitative OCT measurements, but there appeared to be a mild trend toward improved anatomy and qualitative OCT findings when topical nepafenac was added to monthly anti-VEGF injections in patients with persistent intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Further prospective studies with longer follow-up may be warranted. PMID:21151329

Chen, Eric; Benz, Matthew S; Fish, Richard H; Brown, David M; Wong, Tien P; Kim, Rosa Y; Major, James C

2010-01-01

355

Molecular Biology and Biotechnology of Flower Pigments  

Microsoft Academic Search

\\u000a The major pigments responsible for flower colour are flavonoids (particularly anthocyanins) and carotenoids, with betalains\\u000a occurring in a relatively small number of species. Flavonoids and betalains are water-soluble and generally located in the\\u000a vacuole. Carotenoids are lipid-soluble, plastid-located terpenoids, which for pigmentation of flowers accumulate in specialized\\u000a plastids called chromoplasts. The biosynthetic pathways for flavonoids and carotenoids have been characterized

K. M. Davies; K. E. Schwinn

356

Macular Pigment Measurement by Heterochromatic Flicker Photometry in Older Subjects: The Carotenoids and Age-Related Eye Disease Study  

Microsoft Academic Search

METHODS. MPOD in eyes of 54 women, age 50 and 79 years (mean, 66), was studied. The spatial profile of MPOD was measured in the right eye, and two spatial points were also measured in the left eye. Forty-eight of these inexperienced subjects completed the protocol on two separate visits. For a subset of the group, the MPOD at two

D. Max Snodderly; Julie A. Mares; Billy R. Wooten; Lisa Oxton; Michael Gruber

2004-01-01

357

The Aged Retinal Pigment Epithelium\\/Choroid: A Potential Substratum for the Pathogenesis of Age-Related Macular Degeneration  

Microsoft Academic Search

Not Available Bibtex entry for this abstract Preferred format for this abstract (see Preferences) Find Similar Abstracts: Use: Authors Title Return: Query Results Return items starting with number Query Form Database: Astronomy Physics arXiv e-prints

Huiyi Chen; Bin Liu; Thomas J. Lukas; Arthur H. Neufeld; Karl-Wilhelm Koch

2008-01-01

358

Purpose. To evaluate the reliability and validity of a portable instrument for measuring macular pigment optical density.  

E-print Network

exposed to several hours of daylight every day or who used sun beds. Conclusions. The portable instrument, 2002 Correspondence: Prof. John Mellerio, School of Biosciences, University of Westminster, 115 New.J.G.M. van Kuijk3,4 , D. Pauleikhoff5 , A.C. Bird4 and J. Marshall2 1 School of Biosciences, University

359

Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration  

PubMed Central

Aging and oxidative stress seem to be the most important factors in the pathogenesis of age-related macular degeneration (AMD), a condition affecting many elderly people in the developed world. However, aging is associated with the accumulation of oxidative damage in many biomolecules, including DNA. Furthermore, mitochondria may be especially important in this process because the reactive oxygen species produced in their electron transport chain can damage cellular components. Therefore, the cellular response to DNA damage, expressed mainly through DNA repair, may play an important role in AMD etiology. In several studies the increase in mitochondrial DNA (mtDNA) damage and mutations, and the decrease in the efficacy of DNA repair have been correlated with the occurrence and the stage of AMD. It has also been shown that mitochondrial DNA accumulates more DNA lesions than nuclear DNA in AMD. However, the DNA damage response in mitochondria is executed by nucleus-encoded proteins, and thus mutagenesis in nuclear DNA (nDNA) may affect the ability to respond to mutagenesis in its mitochondrial counterpart. We reported that lymphocytes from AMD patients displayed a higher amount of total endogenous basal and oxidative DNA damage, exhibited a higher sensitivity to hydrogen peroxide and UV radiation, and repaired the lesions induced by these factors less effectively than did cells from control individuals. We postulate that poor efficacy of DNA repair (i.e., is impaired above average for a particular age) when combined with the enhanced sensitivity of retinal pigment epithelium cells to environmental stress factors, contributes to the pathogenesis of AMD. Collectively, these data suggest that the cellular response to both mitochondrial and nuclear DNA damage may play an important role in AMD pathogenesis. PMID:23434654

Blasiak, Janusz; Glowacki, Sylwester; Kauppinen, Anu; Kaarniranta, Kai

2013-01-01

360

Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS.  

PubMed

Mutations in the photoreceptor tetraspanin gene peripherin-2/retinal degeneration slow (PRPH2/RDS) cause both rod- and cone-dominant diseases. While rod-dominant diseases, such as autosomal dominant retinitis pigmentosa, are thought to arise due to haploinsufficiency caused by loss-of-function mutations, the mechanisms underlying PRPH2-associated cone-dominant diseases are unclear. Here we took advantage of a transgenic mouse line expressing an RDS mutant (R172W) known to cause macular degeneration (MD) in humans. To facilitate the study of cones in the heavily rod-dominant mouse retina, R172W mice were bred onto an Nrl(-/-) background (in which developing rods adopt a cone-like fate). In this model the R172W protein and the key RDS-binding partner, rod outer segment (OS) membrane protein 1 (ROM-1), were properly expressed and trafficked to cone OSs. However, the expression of R172W led to dominant defects in cone structure and function with equal effects on S- and M-cones. Furthermore, the expression of R172W in cones induced subtle alterations in RDS/ROM-1 complex assembly, specifically resulting in the formation of abnormal, large molecular weight ROM-1 complexes. Fundus imaging demonstrated that R172W mice developed severe clinical signs of disease nearly identical to those seen in human MD patients, including retinal degeneration, retinal pigment epithlium (RPE) defects and loss of the choriocapillaris. Collectively, these data identify a primary disease-causing molecular defect in cone cells and suggest that RDS-associated disease in patients may be a result of this defect coupled with secondary sequellae involving RPE and choriocapillaris cell loss. PMID:24463884

Conley, Shannon M; Stuck, Michael W; Burnett, Justin L; Chakraborty, Dibyendu; Azadi, Seifollah; Fliesler, Steven J; Naash, Muna I

2014-06-15

361

Quantification of External Limiting Membrane Disruption Caused by Diabetic Macular Edema from SD-OCT  

PubMed Central

Purpose. Disruption of external limiting membrane (ELM) integrity on spectral-domain optical coherence tomography (SD-OCT) is associated with lower visual acuity outcomes in patients suffering from diabetic macular edema (DME). However, no automated methods to detect ELM and/or determine its integrity from SD-OCT exist. Methods. Sixteen subjects diagnosed with clinically significant DME (CSME) were included and underwent macula-centered SD-OCT (512 × 19 × 496 voxels). Sixteen subjects without retinal thickening and normal acuity were also scanned (200 × 200 × 1024 voxels). Automated quantification of ELM disruption was achieved as follows. First, 11 surfaces were automatically segmented using our standard 3-D graph-search approach, and the subvolume between surface 6 and 11 containing the ELM region was flattened based on the segmented retinal pigment epithelium (RPE) layer. A second, edge-based graph-search surface-detection method segmented the ELM region in close proximity “above” the RPE, and each ELM A-scan was classified as disrupted or nondisrupted based on six texture features in the vicinity of the ELM surface. The vessel silhouettes were considered in the disruption classification process to avoid false detections of ELM disruption. Results. In subjects with CSME, large areas of disrupted ELM were present. In normal subjects, ELM was largely intact. The mean and 95% confidence interval (CI) of the detected disruption area volume for normal and CSME subjects were meannormal = 0.00087 mm3 and CInormal = (0.00074, 0.00100), and meanCSME = 0.00461 mm3 and CICSME = (0.00347, 0.00576) mm3, respectively. Conclusions. In this preliminary study, we were able to show that automated quantification of ELM disruption is feasible and can differentiate continuous ELM in normal subjects from disrupted ELM in subjects with CSME. We have started determining the relationships of quantitative ELM disruption markers to visual outcome in patients undergoing treatment for CSME. PMID:23111607

Chen, Xinjian; Zhang, Li; Sohn, Elliott H.; Lee, Kyungmoo; Niemeijer, Meindert; Chen, John; Sonka, Milan; Abramoff, Michael D.

2012-01-01

362

Relationship between Retinal Layer Thickness and the Visual Field in Early Age-Related Macular Degeneration  

PubMed Central

Purpose. To quantify and compare the structural and functional changes in subjects with early age-related macular degeneration (AMD), using spectral-domain optical coherence tomography (SD-OCT) and microperimetry. Methods. Twenty-one eyes of 21 subjects with early AMD were examined. MP-1 10-2 visual fields (VFs) and SD-OCT line and detail volume scans were acquired. The thicknesses of the outer segment (OS; distance between inner segment ellipsoid band and upper retinal pigment epithelium [RPE] border) and RPE layers and elevation of the RPE from Bruch's membrane were measured using a computer-aided manual segmentation technique. Thickness values were compared with those for 15 controls, and values at locations with VF total deviation defects were compared with values at nondefect locations at equivalent eccentricities. Results. Sixteen of 21 eyes with AMD had VF defects. Compared with controls, line scans showed significant thinning of the OS layer (P = 0.006) and thickening and elevation of the RPE (P = 0.037, P = 0.002). The OS layer was significantly thinner in locations with VF defects compared with locations without defects (P = 0.003). There was a negligible difference between the retinal layer thickness values of the 5 eyes without VF defects and the values of normal controls. Conclusions. In early AMD, when VF defects were present, there was significant thinning of the OS layer and thickening and elevation of the RPE. OS layer thinning was significantly associated with decreased visual sensitivity, consistent with known photoreceptor loss in early AMD. For AMD subjects without VF defects, thickness values were normal. The results highlight the clinical utility of both SD-OCT retinal layer quantification and VF testing in early AMD. PMID:23074210

Acton, Jennifer H.; Smith, R. Theodore; Hood, Donald C.; Greenstein, Vivienne C.

2012-01-01

363

Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye.  

PubMed

Two-photon excitation microscopy can image retinal molecular processes in vivo. Intrinsically fluorescent retinyl esters in subcellular structures called retinosomes are an integral part of the visual chromophore regeneration pathway. Fluorescent condensation products of all-trans-retinal accumulate in the eye with age and are also associated with age-related macular degeneration (AMD). Here, we report repetitive, dynamic imaging of these compounds in live mice through the pupil of the eye. By leveraging advanced adaptive optics, we developed a data acquisition algorithm that permitted the identification of retinosomes and condensation products in the retinal pigment epithelium by their characteristic localization, spectral properties and absence in genetically modified or drug-treated mice. This imaging approach has the potential to detect early molecular changes in retinoid metabolism that trigger light- and AMD-induced retinal defects and to assess the effectiveness of treatments for these conditions. PMID:24952647

Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Hunter, Jennifer J; Williams, David R; Alexander, Nathan S; Palczewski, Krzysztof

2014-07-01

364

Retinal layer segmentation of macular OCT images using boundary classification.  

PubMed

Optical coherence tomography (OCT) has proven to be an essential imaging modality for ophthalmology and is proving to be very important in neurology. OCT enables high resolution imaging of the retina, both at the optic nerve head and the macula. Macular retinal layer thicknesses provide useful diagnostic information and have been shown to correlate well with measures of disease severity in several diseases. Since manual segmentation of these layers is time consuming and prone to bias, automatic segmentation methods are critical for full utilization of this technology. In this work, we build a random forest classifier to segment eight retinal layers in macular cube images acquired by OCT. The random forest classifier learns the boundary pixels between layers, producing an accurate probability map for each boundary, which is then processed to finalize the boundaries. Using this algorithm, we can accurately segment the entire retina contained in the macular cube to an accuracy of at least 4.3 microns for any of the nine boundaries. Experiments were carried out on both healthy and multiple sclerosis subjects, with no difference in the accuracy of our algorithm found between the groups. PMID:23847738

Lang, Andrew; Carass, Aaron; Hauser, Matthew; Sotirchos, Elias S; Calabresi, Peter A; Ying, Howard S; Prince, Jerry L

2013-07-01

365

Occupational pigmented contact dermatitis from Naphthol AS.  

PubMed

Hyper-pigmentation as a manifestation of contact sensitivity to optical brighteners has previously been reported. In 1973 we observed an epidemic of pigmented contact dermatitis occurring in a textile mill in connection with the manufacture of drill fabrics impregnated with a recently introduced azo dye coupling component Naphthol AS. Of the 53 workers included in the study, 12 presented a spotted pattern of hyperpigmentation mainly affecting the exposed areas, but without pruritus, 18 were pigmented to a lesser degree, and in 21 it was not possible to discern any well-defined discoloration; some of the patients in the last group, however, complained of slight pruritus. The last two patients who were fair-skinned showed a reddish-brown pigmentation and a well pronounced pruritus. Hyper-pigmentation was most pronounced in individuals with dark complexions, whereas fair-skinned patient also showed "classical" eczematous symptoms including pruritus. A field study demonstrated direct exposure to the chemical. All 53 patients were patch-tested with Naphthol AS 5% in water, and 24 were found to be positive. Histological features were melanocyte proliferation, incontinence of pigment, and various degrees of damage to the basal layer. PMID:139268

Ancona-Alayón, A; Escobar-Márques, R; Gonález-Mendoza, A; Bernal-Tapia, J A; Macotela-Ruíz, E; Jurado-Mendoza, J

1976-06-01

366

Trade-Offs between Predation Risk and Growth Benefits in the Copepod Eurytemora affinis with Contrasting Pigmentation  

PubMed Central

Intraspecific variation in body pigmentation is an ecologically and evolutionary important trait; however, the pigmentation related trade-offs in marine zooplankton are poorly understood. We tested the effects of intrapopulation phenotypic variation in the pigmentation of the copepod Eurytemora affinis on predation risk, foraging, growth, metabolic activity and antioxidant capacity. Using pigmented and unpigmented specimens, we compared (1) predation and selectivity by the invertebrate predator Cercopagis pengoi, (2) feeding activity of the copepods measured as grazing rate in experiments and gut fluorescence in situ, (3) metabolic activity assayed as RNA:DNA ratio in both experimental and field-collected copepods, (4) reproductive output estimated as egg ratio in the population, and (5) total antioxidant capacity. Moreover, mitochondrial DNA (mtDNA) COI gene variation was analysed. The pigmented individuals were at higher predation risk as evidenced by significantly higher predation rate by C. pengoi on pigmented individuals and positive selection by the predator fed pigmented and unpigmented copepods in a mixture. However, the antioxidant capacity, RNA:DNA and egg ratio values were significantly higher in the pigmented copepods, whereas neither feeding rate nor gut fluorescence differed between the pigmented and unpigmented copepods. The phenotypic variation in pigmentation was not associated with any specific mtDNA genotype. Together, these results support the metabolic stimulation hypothesis to explain variation in E. affinis pigmentation, which translates into beneficial increase in growth via enhanced metabolism and antioxidant protective capacity, together with disadvantageous increase in predation risk. We also suggest an alternative mechanism for the metabolic stimulation via elevated antioxidant levels as a primary means of increasing metabolism without the increase in heat absorbance. The observed trade-offs are relevant to evolutionary mechanisms underlying plasticity and adaptation and have the capacity to modify strength of complex trophic interactions. PMID:23940745

Gorokhova, Elena; Lehtiniemi, Maiju; Motwani, Nisha H.

2013-01-01

367

Trade-offs between predation risk and growth benefits in the copepod Eurytemora affinis with contrasting pigmentation.  

PubMed

Intraspecific variation in body pigmentation is an ecologically and evolutionary important trait; however, the pigmentation related trade-offs in marine zooplankton are poorly understood. We tested the effects of intrapopulation phenotypic variation in the pigmentation of the copepod Eurytemora affinis on predation risk, foraging, growth, metabolic activity and antioxidant capacity. Using pigmented and unpigmented specimens, we compared (1) predation and selectivity by the invertebrate predator Cercopagis pengoi, (2) feeding activity of the copepods measured as grazing rate in experiments and gut fluorescence in situ, (3) metabolic activity assayed as RNA:DNA ratio in both experimental and field-collected copepods, (4) reproductive output estimated as egg ratio in the population, and (5) total antioxidant capacity. Moreover, mitochondrial DNA (mtDNA) COI gene variation was analysed. The pigmented individuals were at higher predation risk as evidenced by significantly higher predation rate by C. pengoi on pigmented individuals and positive selection by the predator fed pigmented and unpigmented copepods in a mixture. However, the antioxidant capacity, RNA:DNA and egg ratio values were significantly higher in the pigmented copepods, whereas neither feeding rate nor gut fluorescence differed between the pigmented and unpigmented copepods. The phenotypic variation in pigmentation was not associated with any specific mtDNA genotype. Together, these results support the metabolic stimulation hypothesis to explain variation in E. affinis pigmentation, which translates into beneficial increase in growth via enhanced metabolism and antioxidant protective capacity, together with disadvantageous increase in predation risk. We also suggest an alternative mechanism for the metabolic stimulation via elevated antioxidant levels as a primary means of increasing metabolism without the increase in heat absorbance. The observed trade-offs are relevant to evolutionary mechanisms underlying plasticity and adaptation and have the capacity to modify strength of complex trophic interactions. PMID:23940745

Gorokhova, Elena; Lehtiniemi, Maiju; Motwani, Nisha H

2013-01-01

368

Fucoidan reduces secretion and expression of vascular endothelial growth factor in the retinal pigment epithelium and reduces angiogenesis in vitro.  

PubMed

Fucoidan is a polysaccharide isolated from brown algae which is of current interest for anti-tumor therapy. In this study, we investigated the effect of fucoidan on the retinal pigment epithelium (RPE), looking at physiology, vascular endothelial growth factor (VEGF) secretion, and angiogenesis, thus investigating a potential use of fucoidan for the treatment of exudative age-related macular degeneration. For this study, human RPE cell line ARPE-19 and primary porcine RPE cells were used, as well as RPE/choroid perfusion organ cultures. The effect of fucoidan on RPE cells was investigated with methyl thiazolyl tetrazolium--assay, trypan blue exclusion assay, phagocytosis assay and a wound healing assay. VEGF expression was evaluated in immunocytochemistry and Western blot, VEGF secretion was evaluated in ELISA. The effect of fucoidan on angiogenesis was tested in a Matrigel assay using calcein-AM vital staining, evaluated by confocal laser scanning microcopy and quantitative image analysis. Fucoidan displays no toxicity and does not diminish proliferation or phagocytosis, but reduces wound healing in RPE cells. Fucoidan decreases VEGF secretion in RPE/choroid explants and RPE cells. Furthermore, it diminishes VEGF expression in RPE cells even when co-applied with bevacizumab. Furthermore, fucoidan reduces RPE-supernatant- and VEGF-induced angiogenesis of peripheral endothelial cells. In conclusion, fucoidan is a non-toxic agent that reduces VEGF expression and angiogenesis in vitro and may be of interest for further studies as a potential therapy against exudative age-related macular degeneration. PMID:24558482

Dithmer, Michaela; Fuchs, Sabine; Shi, Yang; Schmidt, Harald; Richert, Elisabeth; Roider, Johann; Klettner, Alexa

2014-01-01

369

Clinical characteristics of pigment dispersion syndrome in Chinese patients  

Microsoft Academic Search

PurposeTo report clinical findings and characteristics of pigment dispersion syndrome (PDS) in Chinese patients.MethodsPDS suspects with any one of the following signs: corneal endothelial pigmentation, iris transillumination defects (ITDs), pigment granule dusting on anterior iris surface, posterior iris bowing, trabecular meshwork (TM) pigmentation, and lenticular or zonular pigmentation were evaluated for PDS at the glaucoma specialty clinic at Beijing Tongren

G Qing; N Wang; X Tang; S Zhang; H Chen

2009-01-01

370

Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images  

PubMed Central

We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases. PMID:25360373

Srinivasan, Pratul P.; Kim, Leo A.; Mettu, Priyatham S.; Cousins, Scott W.; Comer, Grant M.; Izatt, Joseph A.; Farsiu, Sina

2014-01-01

371

Fully automated detection of diabetic macular edema and dry age-related macular degeneration from optical coherence tomography images.  

PubMed

We present a novel fully automated algorithm for the detection of retinal diseases via optical coherence tomography (OCT) imaging. Our algorithm utilizes multiscale histograms of oriented gradient descriptors as feature vectors of a support vector machine based classifier. The spectral domain OCT data sets used for cross-validation consisted of volumetric scans acquired from 45 subjects: 15 normal subjects, 15 patients with dry age-related macular degeneration (AMD), and 15 patients with diabetic macular edema (DME). Our classifier correctly identified 100% of cases with AMD, 100% cases with DME, and 86.67% cases of normal subjects. This algorithm is a potentially impactful tool for the remote diagnosis of ophthalmic diseases. PMID:25360373

Srinivasan, Pratul P; Kim, Leo A; Mettu, Priyatham S; Cousins, Scott W; Comer, Grant M; Izatt, Joseph A; Farsiu, Sina

2014-10-01

372

The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells  

PubMed Central

Proteins involved in cholesterol trafficking are known to contribute to the pathogenesis of atherosclerosis and Alzheimer's disease. Allelic variants in the cholesterol transporters apolipoprotein E and ATP-binding cassette protein A1 (ABCA1) have recently been associated with susceptibility to age-related macular degeneration (AMD). Histopathological analyses of eyes with AMD demonstrate the presence of cholesterol and cholesteryl ester deposits beneath the retinal pigment epithelium (RPE), implicating abnormal cholesterol trafficking in disease progression. Here, we show that A2E, a quaternary amine and retinoid by-product of the visual cycle, causes the accumulation of free and esterified cholesterol in RPE cells. The mechanism involves neither generalized alterations in late endosomal/lysosomal pH nor a direct inhibition of acid lipase activity. Rather, A2E prevents cholesterol efflux from these organelles, which in turn indirectly inhibits acid lipase, leading to a subsequent accumulation of cholesteryl esters. Transcriptional activation of the ABCA1 cholesterol transporter by agonists of the liver X receptor/peroxisome proliferator-activated receptor pathway relieves the A2E-induced block on cholesterol efflux and restores cholesterol homeostasis in RPE cells. Our data also demonstrate that A2E, which is a cone-shaped lipid, increases the chemical activity and displacement of cholesterol from model membranes, providing a biophysical mechanism for cholesterol sequestration in A2E-loaded cells. Although endogenously produced A2E in the RPE has been associated with macular degeneration, the precise mechanisms are unclear. Our results provide direct evidence that A2E causes aberrant cholesterol metabolism in RPE cells which could likely contribute to AMD progression. PMID:17578916

Lakkaraju, Aparna; Finnemann, Silvia C.; Rodriguez-Boulan, Enrique

2007-01-01

373

Complement Factor H 402H Variant and Reticular Macular Disease  

PubMed Central

Objective To determine the association of high-risk alleles in the complement factor H (CFH; Y402H, rs1061170) and age-related maculopathy susceptibility (ARMS2; A69S, rs10490924) genes with reticular macular disease (RMD), a major clinical subphenotype of age-related macular degeneration (AMD). Methods Using retinal images from the Columbia Macular Genetics Study, we identified 67 subject individuals with RMD. A comparison group of 64 subjects with AMD without RMD was matched by ethnicity, age, sex, and AMD clinical stage. Results In the RMD group, 53 of 67 subjects (79.1%) were female, the mean age was 83 years, and 47 of 67 (70.1%) had late AMD, with closely matched values in the non-RMD group. The frequencies of the CFH 402H allele were 39.6% in the RMD group (53 of 134 individuals) and 58.6% in the non-RMD group (75 of 128 individuals) (?2=8.8; P=.003; odds ratio, 0.46 [95% confidence interval, 0.28–0.76]). The corresponding frequencies of the risk allele for ARMS2 were 44.0% (40 of 128 individuals) and 31.3% (40 of 128 individuals), respectively (?2=4.0; P=.045; odds ratio, 1.73 [95% confidence interval, 1.04–2.90]). Homozygosity for 402Hwas particularly associated with the absence of RMD, occurring in 8 of 67 subjects (11.9%) with RMD vs 24 of 64 subjects (37.5%) without RMD(P ?.001). Retinal macular disease also was associated with hypertension among male patients. Conclusions The AMD-associated CFH 402H risk variant is significantly associated with the absence of RMD but enhanced risk for RMD is conferred by the ARMS2 69S AMD risk allele. These results are consistent with the hypothesis that 402H may confer a survival benefit against certain infections, some of which may cause RMD. Clinical Relevance Reticular macular disease may be genetically distinct from the rest of AMD. PMID:21825189

Smith, R. Theodore; Merriam, Joanna E.; Sohrab, Mahsa A.; Pumariega, Nicole M.; Barile, Gaetano; Blonska, Anna M.; Haans, Raymond; Madigan, David; Allikmets, Rando

2013-01-01

374

Analysis of macular cone photoreceptors in a case of occult macular dystrophy  

PubMed Central

Purpose To investigate changes in cone photoreceptors with adaptive optics (AO) fundus imaging and spectral domain optical coherence tomography (SD-OCT) in a case of occult macular dystrophy (OMD). Patient and methods Both eyes of a 42-year-old woman diagnosed with OMD were examined. We used an AO fundus camera to obtain images of cone photoreceptors in the macula of the OMD subject and five healthy control subjects. Correlations between the AO images and the SD-OCT images were examined. Cone photoreceptors in eight areas in the macula of OMD and healthy control subjects were analyzed and compared. Results SD-OCT showed a loss of the cone outer-segment tips line outside of the fovea in both eyes of the subject with OMD. The left eye with decreased visual acuity showed a discontinuous photoreceptor inner-segment and outer-segment line and cone outer-segment tips line at the fovea in SD-OCT and loss of cone mosaics as a dark spot in the AO image. In panoramic AO images and cone-density maps, less cone density was observed in a ring-like region outside the fovea than in the peripheral retina. In most of the areas examined, the cone densities were lower in the OMD eyes than in the healthy control eyes. Conclusions Cone densities in the macula of the OMD patient were greatly decreased. AO images were found to be useful to evaluate morphologic changes in cone photoreceptors in patients with OMD. PMID:23696695

Tojo, Naoki; Nakamura, Tomoko; Ozaki, Hironori; Oka, Miyako; Oiwake, Toshihiko; Hayashi, Atsushi

2013-01-01

375

Refining the locus for Best vitelliform macular dystrophy and mutation analysis of the candidate gene ROM1  

Microsoft Academic Search

Vitelliform macular dystrophy (Best disease) is an autosomal dominant macular dystrophy which shares important clinical features with age-related macular degeneration, the most common cause of legal blindness in the elderly. Unfortunately, understanding and treatment for this common age-related disorder is limited. Discovery of the gene which causes Best disease has the potential to increase the understanding of the pathogenesis of

B. E. Nichols; E. M. Stone; V. C. Sheffield; R. McInnes; R. Bascom; M. Litt

1994-01-01

376

The role of CRP and inflammation in the pathogenesis of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving the multiple genetic and environmental factors that can result in severe visual loss. The etiology of AMD is not well understood. Many theories exist and feature mechanisms of oxidative stress, atherosclerotic-like changes, genetic predisposition and inflammation. The most recent clinical studies appointed to a great role of inflammation and C-reactive protein (CRP) in the pathogenesis of AMD. There is a large body of evidence indicating the association of CRP with endothelial dysfunction, oxidative stress and production of reactive oxygen species (ROS), as well as with lipid status disorder in AMD patients. According to recent studies, CRP is definitely not only the inflammatory marker but also a mediator of development of the vascular disorders in the retinal circulation. The results obtained from the present studies may help our understanding the pathogenesis of the retinal vascular disease associated with high levels of CRP. PMID:22384518

Colak, Emina; Majkic-Singh, Nada; Zoric, Lepsa; Radosavljevic, Aleksandra; Kosanovic-Jakovic, Natalija

2012-01-01

377

Hypomethylation of IL17RC Promoter Associates with Age-related Macular Degeneration  

PubMed Central

SUMMARY Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its etiology. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. PMID:23177625

Wei, Lai; Liu, Baoying; Tuo, Jingsheng; Shen, Defen; Chen, Ping; Li, Zhiyu; Liu, Xunxian; Ni, Jia; Dagur, Pradeep; Sen, H. Nida; Jawad, Shayma; Ling, Diamond; Park, Stanley; Chakrabarty, Sagarika; Meyerle, Catherine; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.; McCoy, J. Philip; Blum, Emily; Francis, Peter J.; Klein, Michael L.; Guymer, Robyn H.; Baird, Paul N.; Chan, Chi-Chao; Nussenblatt, Robert B.

2012-01-01

378

Modular Spectral Imaging System for Discrimination of Pigments in Cells and Microbial Communities? †  

PubMed Central

Here we describe a spectral imaging system for minimally invasive identification, localization, and relative quantification of pigments in cells and microbial communities. The modularity of the system allows pigment detection on spatial scales ranging from the single-cell level to regions whose areas are several tens of square centimeters. For pigment identification in vivo absorption and/or autofluorescence spectra are used as the analytical signals. Along with the hardware, which is easy to transport and simple to assemble and allows rapid measurement, we describe newly developed software that allows highly sensitive and pigment-specific analyses of the hyperspectral data. We also propose and describe a number of applications of the system for microbial ecology, including identification of pigments in living cells and high-spatial-resolution imaging of pigments and the associated phototrophic groups in complex microbial communities, such as photosynthetic endolithic biofilms, microbial mats, and intertidal sediments. This system provides new possibilities for studying the role of spatial organization of microorganisms in the ecological functioning of complex benthic microbial communities or for noninvasively monitoring changes in the spatial organization and/or composition of a microbial community in response to changing environmental factors. PMID:19074609

Polerecky, Lubos; Bissett, Andrew; Al-Najjar, Mohammad; Faerber, Paul; Osmers, Harald; Suci, Peter A.; Stoodley, Paul; de Beer, Dirk

2009-01-01

379

Human hair melanins: what we have learned and have not learned from mouse coat color pigmentation.  

PubMed

Hair pigmentation is one of the most conspicuous phenotypes in humans. Melanocytes produce two distinct types of melanin pigment: brown to black, indolic eumelanin and yellow to reddish brown, sulfur-containing pheomelanin. Biochemically, the precursor tyrosine and the key enzyme tyrosinase and the tyrosinase-related proteins are involved in eumelanogenesis, while only the additional presence of cysteine is necessary for pheomelanogenesis. Other important proteins involved in melanogenesis include P protein, MATP protein, ?-MSH, agouti signaling protein (ASIP), MC1R (the receptor for MSH and ASIP), and SLC7A11, a cystine transporter. Many studies have examined the effects of loss-of-function mutations of those proteins on mouse coat color pigmentation. In contrast, much less is known regarding the effects of mutations of the corresponding proteins on human hair pigmentation except for MC1R polymorphisms that lead to pheomelanogenesis. This perspective will discuss what we have/have not learned from mouse coat color pigmentation, with special emphasis on the significant roles of pH and the level of cysteine in melanosomes in controlling melanogenesis. Based on these data, a hypothesis is proposed to explain the diversity of human hair pigmentation. PMID:20726950

Ito, Shosuke; Wakamatsu, Kazumasa

2011-02-01

380

Dietary Restriction Slows Age Pigment Accumulation in the Retinal Pigment Epithelium  

Microsoft Academic Search

Purpose. The accumulation of age pigment, or lipofuscin, in postmitotic cells appears to be a universal feature of the aging process in animals. In mammals, the lipofuscin content of the retinal pigment epithelium (RPE) increases progressively during senescence. Dietary restric- tion has been shown to slow the rate at which many biologic parameters change during aging. Experiments were conducted to

Martin L. Katz; Heather A. White; Chun-Lan Gao; George S. Roth; Donald K. Ingram

1993-01-01

381

Betalain: a particular class of antioxidant pigment.  

PubMed

We have analyzed the stability of betalains in juices prepared from Moroccan yellow cactus pears (Opuntia ficus indica (L.) Mill.) as a function of temperature and pH. The experiments were carried out at temperatures ranging from 80 to 100 degrees C with juices at pH 3.5, 5 and 6.5. The degree of pigment retention decreased when the temperature increased. The degradation constant rates were determined for thermal degradation rates of pseudo-first order. The Arrhenius plot obtained for the degradation of betaxanthin from the yellow fruits was not linear. Regardless of the temperature of treatment, the lowest degradation was obtained for pH 5. When some stabilizers were tested for the protection of pigments, the results showed that ascorbic acid was a better protective agent at pH 3.5, increasing the protection by 40%. The inhibitive action of betalain pigments extracted from cactus pears towards corrosion of stainless steel in phosphoric acid was investigated using electrochemical polarization and electrochemical impedance spectroscopy (EIS) methods. It was found that the presence of natural pigments reduces the corrosion rate of the tested metal, especially on addition of the red pigments (97%). The inhibition efficiency increases as the pigment concentration of extracts increases. It was also found that the pigments tested act as mixed inhibitors. The inhibitive action of the extracts is discussed in term of adsorption and that such adsorption follows a Langmuir adsorption isotherm. The calculated values of the free energy of adsorption indicated that the adsorption process is spontaneous. PMID:22164774

El Gharras, Hasna

2011-10-01

382

[Triamcinolone acetonide bevacizumab performance in treatment and idiopathic macular spider veins].  

PubMed

This article evaluated the efficacy of intravitrean injection of anti VEGF agents and triamcinolon in the treatment of macular telangiectasis. The patients were followed six months. We practiced fluorescein angiography, optical coherence tomography. We measured the thickening of macular edema and best corrected of visual acuity. PMID:20540378

Cerbulescu, Beatrice; Taina, Ana-Lavinia; Dinita, Monica; Malaeanu, Raluca; Radocea, Robertina; Carstocea, B

2010-01-01

383

Automatic detection of age-related macular degeneration pathologies in retinal fundus images  

Microsoft Academic Search

Advanced techniques in image processing and analysis are being extensively studied to assist clinical diagnoses. Digital colour retinal fundus images are widely utilised to investigate various eye diseases. In this paper, we describe the detection of optic disc (OD), macula and age-related macular degeneration (ARMD) pathologies of the macular regions in colour fundus images. ARMD causes the loss of central

Ay?egül Güven

2012-01-01

384

Treatment of retinal detachment resulting from myopic macular hole with internal limiting membrane removal  

Microsoft Academic Search

PURPOSE: To examine the efficacy of vitrectomy with internal limiting membrane removal for retinal detachment resulting from a macular hole in highly myopic eyes.METHODS: Eleven consecutive highly myopic eyes (11 patients) with retinal detachment resulting from a macular hole were treated by vitrectomy with removal of the internal limiting membrane, which was stained with indocyanine green and sulfur hexafluoride gas

Kazuaki Kadonosono; Futoshi Yazama; Norihiko Itoh; Eiichi Uchio; Satoshi Nakamura; Junsuke Akura; Hajime Sawada; Shigeaki Ohno

2001-01-01

385

Effect of infusion air pressure on visual field defects after macular hole surgery  

Microsoft Academic Search

PURPOSE: A defect in the visual field is one of the serious complications of macular hole surgery. We investigated the relationship between the occurrence of visual field defect and the location of infusion cannula and air pressure during fluid–air exchange.METHODS: We studied 100 eyes from 90 patients with macular holes. All patients underwent preoperative and postoperative visual field testing. Vitreous

Akira Hirata; Naoko Yonemura; Tadashi Hasumura; Yasuhiro Murata; Akira Negi

2000-01-01

386

Associations between Lutein, Zeaxanthin, and Age-Related Macular Degeneration: An Overview  

Microsoft Academic Search

Age-related macular degeneration, the leading cause of blindness in the elderly, is a degenerative condition of the macula characterized by death or dysfunction of the photoreceptors. With the aging population growing, the incidence of age-related macular degeneration is expected to increase. This raises concern about the future of visual dysfunction related falls and the resulting injuries in the elderly population.

Shannon Carpentier; Maria Knaus; Miyoung Suh

2009-01-01

387

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)  

Microsoft Academic Search

Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of macular degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease.

Hema L. Ramkumar; Jun Zhang; Chi-Chao Chan

2010-01-01

388

Ranibizumab for Macular Edema Due to Retinal Vein Occlusions: Implication of VEGF as a Critical Stimulator  

Microsoft Academic Search

Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO

Peter A Campochiaro; Gulnar Hafiz; Syed Mahmood Shah; Quan Dong Nguyen; Howard Ying; Diana V Do; Edward Quinlan; Ingrid Zimmer-Galler; Julia A Haller; Sharon D Solomon; Jennifer U Sung; Yasmin Hadi; Kashif A Janjua; Nida Jawed; David F Choy; Joseph R Arron

2008-01-01

389

Bilateral and simultaneous cystoid macular edema associated with latanoprost use: report of two cases.  

PubMed

Cystoid macular edema is an uncommon, but well known, side effect of latanoprost. Two cases of bilateral and simultaneous cystoid macular edema associated with latanoprost use are described, which complete resolution of the edema is observed upon drug discontinuation. PMID:20549052

Brasil, Oswaldo Ferreira Moura; Brasil, Maria Vitoria Moura; Ventura, Marcelo Palis; Maia, Hugo Soares

2010-01-01

390

Simple Estimation of Clinically Relevant Lesion Volumes Using Spectral Domain–Optical Coherence Tomography in Neovascular Age-Related Macular Degeneration  

PubMed Central

Purpose. To evaluate simple methods of estimating the volume of clinically relevant features in neovascular age-related macular degeneration (NVAMD) using spectral domain–optical coherence tomography (SD-OCT). Methods. Using a database of NVAMD cases imaged with macular cube (512 A-scans × 128 B-scans) SD-OCT scans, the authors retrospectively selected visits where cystoid macular edema (CME), subretinal fluid (SRF), or pigment epithelial detachments (PEDs) were evident. Patients with single visits were analyzed in the cross-sectional analysis (CSA) and those with a baseline visit and three or more follow-up visits in the longitudinal analysis (LA). The volume of each feature was measured by manual grading using validated grading software. Simplified measurements for each feature included: number of B-scans or A-scans involved and maximum height. Automated measurements of total macular volume and foveal central subfield were also collected from each machine. Correlations were performed between the volumes measured with 3D-OCTOR, automated measurements, and the simplified measures. Results. Forty-five visits for 25 patients were included in this study: 26 cube scans from 26 eyes of 25 patients in the CSA and 24 scans from 5 eyes of 5 patients in the LA. The simplified measures that correlated best with manual grading in the CSA group were maximum lesion height for CME (r2 value = 0.96) and B-scan count for SRF and PED volume (r2 values of 0.88 and 0.70). In the LA group, intervisit differences were correlated. Change in B-scan count correlated well with change in SRF volume (r2 = 0.97), whereas change in maximum height correlated with change in CME and PED volume (r2 = 0.98 and 0.43, respectively). Conclusions. These data suggest that simplified estimators of some NVAMD lesion volumes exist and are accessible by clinicians without the need for specialized software or time-consuming manual segmentation. These simple approaches could enhance quantitative disease monitoring strategies in clinical trials and clinical practice. PMID:21862646

Heussen, Florian M.; Ouyang, Yanling; Sadda, SriniVas R.

2011-01-01

391

The Origin of the Drosophila Subretinal Pigment Layer  

PubMed Central

Optical insulation plays a critical role in the fine visual acuity of the Drosophila compound eye. Screening pigments expressed by a number of cell types contribute to this phenomenon. They provide optical insulation that prevents extraneous light rays from inappropriately activating the photoreceptors. This optical insulation can be divided into two categories; the insulation of the individual ommatidia, and the insulation of the compound eye as a whole. The whole-eye insulation is provided by two sources. The sides of the eye are optically insulated by the pigment rim, a band of pigment cells that circumscribes the eye. The base of the eye is insulated by the subretinal pigment layer; a thick layer of pigment that lies directly underneath the retina. How this subretinal pigment layer is generated has not been clearly described. Here, experiments that manipulate pigment expression during eye development suggest that the subretinal pigment layer is directly derived from pigment cells in the overlying retina. PMID:22684937

Tomlinson, Andrew

2014-01-01

392

Unilateral recurrent macular hole in a patient with retinitis pigmentosa: a case report  

PubMed Central

Introduction Several macular complications related to abnormalities of the vitreoretinal interface have been classically attributed to retinitis pigmentosa of which cystoid macular edema is the most common. Other less frequent complications are as follows: epiretinal membranes, vitreomacular traction syndrome and macular holes. Case presentation A 64-year-old woman, with the previous diagnosis of retinitis pigmentosa, was referred to our department with a complaint of central visual loss in her left eye for 12?months. A fundoscopy and optical coherence tomography examination revealed the presence of a macular hole more than 500?microns in diameter. The patient underwent 20-gauge pars plana vitrectomy. Closure of the hole was observed after surgery, but reopening occurred at 2?years postoperatively. Conclusion The pathogenesis of macular hole formation in patients with retinitis pigmentosa is unclear. Surgical outcomes may not always be favorable, and the possibility of reopening must be taken into account, even after a long time. PMID:23497416

2013-01-01

393

Intravitreal Injection of Bevacizumab to Treat a Macular Edema Caused by Leber's Miliary Aneurysm  

PubMed Central

Purpose Leber's miliary aneurysm is a variant of Coats’ disease and similar to type 1 idiopathic macular telangiectasia. A recent report showed that an intravitreal injection of bevacizumab (IVB) was effective in an adult patient with type 1 idiopathic macular telangiectasia. We describe our experience with an adult patient with a macular edema caused by Leber's miliary aneurysm, which had not been resolved by prior retinal laser photocoagulation, who underwent IVB. Methods We investigated the ocular characteristics of the patient before and after a single administration of IVB. Results The macular edema had partially improved 1 month after IVB, but then it worsened. We performed laser photocoagulation to treat the aneurysms near the fovea. The macular edema improved, but there was no improvement in visual acuity. Conclusion In this patient, the effect of IVB was limited. PMID:23275795

Takeyama, Masayuki; Iwaki, Masayoshi; Zako, Masahiro

2012-01-01

394

Inadvertent Polychlorinated Biphenyls in Commercial Paint Pigments  

PubMed Central

A polychlorinated biphenyl (PCB) that was not produced as part of the Aroclor mixtures banned in the 1980s was recently reported in air samples collected in Chicago, Philadelphia, the Arctic, and several sites around the Great Lakes. In Chicago, the congener 3,3?-dichlorobiphenyl or PCB11 was found to be the fifth most concentrated congener and ubiquitous throughout the city. The congener exhibited strong seasonal concentration trends that suggest volatilization of this compound from common outdoor surfaces. Due to these findings and also the compound’s presence in waters that received waste from paint manufacturing facilities, we hypothesized that PCB11 may be present in current commercial paint. In this study we measured PCBs in paint sold on the current retail market. We tested 33 commercial paint pigments purchased from three local paint stores. The pigment samples were analyzed for all 209 PCB congeners using gas chromatography with tandem mass spectrometry (GC-MS/MS). More than 50 PCB congeners including several dioxin-like PCBs were detected, and the PCB profiles varied due to different types of pigments and different manufacturing processes. PCB congeners were detected in azo and phthalocyanine pigments which are commonly used in paint but also in inks, textiles, paper, cosmetics, leather, plastics, food and other materials. Our findings suggest several possible mechanisms for the inadvertent production of specific PCB congeners during the manufacturing of paint pigments. PMID:19957996

2009-01-01

395

Inadvertent polychlorinated biphenyls in commercial paint pigments.  

PubMed

A polychlorinated biphenyl (PCB) that was not produced as part of the Aroclor mixtures banned in the 1980s was recently reported in air samples collected in Chicago, Philadelphia, the Arctic, and several sites around the Great Lakes. In Chicago, the congener 3,3'-dichlorobiphenyl or PCB11 was found to be the fifth most concentrated congener and ubiquitous throughout the city. The congener exhibited strong seasonal concentration trends that suggest volatilization of this compound from common outdoor surfaces. Due to these findings and also the compound's presence in waters that received waste from paint manufacturing facilities, we hypothesized that PCB11 may be present in current commercial paint. In this study we measured PCBs in paint sold on the current retail market. We tested 33 commercial paint pigments purchased from three local paint stores. The pigment samples were analyzed for all 209 PCB congeners using gas chromatography with tandem mass spectrometry (GC-MS/MS). More than 50 PCB congeners including several dioxin-like PCBs were detected, and the PCB profiles varied due to different types of pigments and different manufacturing processes. PCB congeners were detected in azo and phthalocyanine pigments which are commonly used in paint but also in inks, textiles, paper, cosmetics, leather, plastics, food and other materials. Our findings suggest several possible mechanisms for the inadvertent production of specific PCB congeners during the manufacturing of paint pigments. PMID:19957996

Hu, Dingfei; Hornbuckle, Keri C

2010-04-15

396

Chlamydomonas reinhardtii in the landscape of pigments.  

PubMed

This review focuses on the biosynthesis of pigments in the unicellular alga Chlamydomonas reinhardtii and their physiological and regulatory functions in the context of information gathered from studies of other photosynthetic organisms. C. reinhardtii is serving as an important model organism for studies of photosynthesis and the pigments associated with the photosynthetic apparatus. Despite extensive information pertaining to the biosynthetic pathways critical for making chlorophylls and carotenoids, we are just beginning to understand the control of these pathways, the coordination between pigment and apoprotein synthesis, and the interactions between the activities of these pathways and those for other important cellular metabolites branching from these pathways. Other exciting areas relating to pigment function are also emerging: the role of intermediates of pigment biosynthesis as messengers that coordinate metabolism in the chloroplast with nuclear gene activity, and the identification of photoreceptors and their participation in critical cellular processes including phototaxis, gametogenesis, and the biogenesis of the photosynthetic machinery. These areas of research have become especially attractive for intensive development with the application of potent molecular and genomic tools currently being applied to studies of C. reinhardtii. PMID:15568974

Grossman, Arthur R; Lohr, Martin; Im, Chung Soon

2004-01-01

397

Investigations of biomimetic light energy harvesting pigments  

SciTech Connect

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Nature uses chlorophyll and other porphyrinic pigments to capture and transfer light energy as a preliminary step in photosynthesis. The design of synthetic assemblies of light harvesting and energy directing pigments has been explored through synthesis and characterization of porphyrin oligomers. In this project, pigment electronic and vibrational structures have been explored by electrochemistry and dynamic and static optical measurements. Transient absorption data reveal energy transfer between pigments with lifetimes on the order of 20--200 picoseconds, while Raman data reveal that the basic porphyrin core structure is unperturbed relative to the individual monomer units. These two findings, along with an extensive series of experiments on the oxidized oligomers, reveal that coupling between the pigments is fundamentally weak, but sufficient to allow facile energy transfer as the predominant excited state process. Modeling of the expected quantum yields for energy transfer within a variety of arrays was accomplished, thereby providing a tool to guide synthetic goals.

Van Patten, P.G.; Donohoe, R.J. [Los Alamos National Lab., NM (United States); Lindsey, J.S. [North Carolina State Univ., Raleigh, NC (United States); Bocian, D.F. [Univ. of California, Riverside, CA (United States)

1998-12-01