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Sample records for macular pigment levels

  1. Aqueous Levels of Pigment Epithelium-Derived Factor and Macular Choroidal Thickness in High Myopia

    PubMed Central

    Chen, Wei; Guan, Yubo; He, Guanghui; Li, Zhiwei; Song, Hui; Xie, Shiyong; Han, Quanhong

    2015-01-01

    Purpose. To investigate the correlation between aqueous and serum levels of pigment epithelium-derived factor (PEDF) and macular choroidal thickness in high myopia patients, both with and without choroidal neovascularization (CNV). Methods. Serum and aqueous levels of PEDF were measured by enzyme-linked immunosorbent assay in 36 high myopia patients (36 eyes) with no CNV (non-CNV group), 14 high myopia patients (14 eyes) with CNV (CNV group), and 42 nonmyopia patients (42 eyes) (control group). Macular choroidal thickness was measured by enhanced-depth imaging optical coherence tomography. Results. Aqueous levels of PEDF were significantly higher in CNV group compared with non-CNV (P < 0.001) and control (P < 0.001) groups. Macular choroidal thicknesses were significantly decreased in the non-CNV and CNV groups compared with the control (P < 0.001) group. A statistically significant difference (P = 0.012) was found between the CNV and non-CNV groups. There was a positive correlation between aqueous PEDF and macular choroidal thickness in the non-CNV group (P = 0.005), but no correlation with the CNV group. No correlation between serum PEDF and macular choroidal thickness was detected in the three groups. Conclusion. Variations in aqueous PEDF levels coincide with changes in macular choroidal thickness in high myopia patients with no CNV, while no such relationship exists in high myopia patients with CNV. PMID:26491554

  2. Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin.

    PubMed

    Beatty, Stephen; Nolan, John; Kavanagh, Heather; O'Donovan, Orla

    2004-10-01

    Observational evidence is accumulating that the onset of age-related maculopathy, the leading cause of legal blindness in the Western World, could be delayed, or even averted, with antioxidant supplements. Lutein (L) and zeaxanthin (Z) are two hydroxy-carotenoids with antioxidant activity which accumulate at the macula, where they are collectively known as macular pigment (MP). It has been shown that MP is entirely of dietary origin, and that L and Z levels in serum, diet, and retina correlate. However, the nature of the relationships between L and Z in foodstuffs, blood, and macula is confounded by many variables including processes which influence digestion, absorption, and transport of the compounds in question, and accumulation and stabilization of the carotenoids in the tissues. If macular pigment is protective for age-related maculopathy, a clear understanding of the mechanisms whereby L and Z arrive at the target tissue (retina) from their source (foodstuff) is essential. In this paper, we review the literature germane to this growing area of interest. PMID:15325913

  3. Measurement of macular pigment optical density in a healthy chinese population sample

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macular pigment may protect against age-related macular degeneration (AMD) by its capability to absorb blue light and scavenge free radicals. Current information on human macular pigment density has been largely from studies on Caucasians populations. The purpose of this study was to assess macular ...

  4. Historic perspectives. Macular yellow pigment. The first 200 years.

    PubMed

    Nussbaum, J J; Pruett, R C; Delori, F C

    1981-01-01

    Since 1782 there has been continuing controversy concerning the curious central coloration referred to as "macular yellow," but no cumulative source of information on the subject exists. This paper reviews the research efforts of two centuries to determine the existence, nature, location, and function of a specialized pigment in the foveal region. Using white-light illumination, it is difficult to see a macular yellow spot in the living eye; it is best observed and documented by red-free ophthalmoscopy and blue-light monochromatic photography. Histologic, biochemical, and spectral absorption data suggest that the yellow color is due to a xanthophyllic pigment, lutein, that is distributed in all retinal layers internal to the outer nuclear layer, with greatest concentration in the outer and inner plexiform layers. Clinically absent in newborns, the pigment gradually accumulates from dietary sources and appears to serve both as an optical filter, by absorbing blue light and reducing chromatic aberration, and in a protective capacity, preventing actinic damage. The absorption characteristics of the yellow pigment contribute to the central dark spot seen during fluorescein angiography and to the risk of photocoagulation near the fovea. Its apparent absence in albinos and the reported functional improvement in certain degenerative retinopathies following supplemental xanthophyll administration suggest a possible role in hereditary or acquired maculopathies. PMID:6758089

  5. A Case of Idiopathic Eruptive Macular Pigmentation Limited to Flexural Areas

    PubMed Central

    Kim, En Hyung; Kim, You Chan

    2008-01-01

    Idiopathic eruptive macular pigmentation is a rare condition characterized by asymptomatic pigmented macules involving the neck, trunk, and proximal portions of the extremities. On histopathologic examination, there was increased pigmentation of the basal layer in otherwise normal epidermis and scattered melanophages in the papillary dermis. We report a case of a 26-year-old woman with idiopathic eruptive macular pigmentation involving only the flexural areas of the body. This condition should be considered in the differential diagnosis of flexural hyperpigmented skin lesions.

  6. Compact single-channel Raman detector for macular pigments

    NASA Astrophysics Data System (ADS)

    Ermakov, Igor V.; Ermakova, Maia R.; Gellermann, Werner

    2004-07-01

    Raman detection of macular pigments (MP) holds promise as a novel noninvasive technology for the quantification of lutein and zeaxanthin carotenoids, which are thought to prevent or delay the onset of age-related macular degeneration. Using resonant excitation in the visible, we measure the Raman signals that originate from the double-bond stretch vibrations of the p-conjugated carotenoid molecule's carbon backbone. In this paper we describe the construction and performance of a new, compact, and low-cost MP Raman instrument using dielectric, angle-tuned band-pass filters for wavelength selection and single-channel photo-multiplier detection of carotenoid Raman responses. MP concentration measurements are fast and accurate, as seen in experiments with model eyes and living human eyes. The ease and rapidity of Raman MP measurements, the relative simplicity of the instrumentation, the high accuracy of the measurements, and the lack of significant systematic errors should make this technology useful for widespread clinical research.

  7. Structure and Conformation of the Carotenoids in Human Retinal Macular Pigment.

    PubMed

    Arteni, Ana-Andreea; Fradot, Mathias; Galzerano, Denise; Mendes-Pinto, Maria M; Sahel, José-Alain; Picaud, Serge; Robert, Bruno; Pascal, Andrew A

    2015-01-01

    Human retinal macular pigment (MP) is formed by the carotenoids lutein and zeaxanthin (including the isomer meso-zeaxanthin). MP has several functions in improving visual performance and protecting against the damaging effects of light, and MP levels are used as a proxy for macular health-specifically, to predict the likelihood of developing age-related macular degeneration. While the roles of these carotenoids in retinal health have been the object of intense study in recent years, precise mechanistic details of their protective action remain elusive. We have measured the Raman signals originating from MP carotenoids in ex vivo human retinal tissue, in order to assess their structure and conformation. We show that it is possible to distinguish between lutein and zeaxanthin, by their excitation profile (related to their absorption spectra) and the position of their ν1 Raman mode. In addition, analysis of the ν4 Raman band indicates that these carotenoids are present in a specific, constrained conformation in situ, consistent with their binding to specific proteins as postulated in the literature. We discuss how these conclusions relate to the function of these pigments in macular protection. We also address the possibilities for a more accurate, consistent measurement of MP levels by Raman spectroscopy. PMID:26313550

  8. Structure and Conformation of the Carotenoids in Human Retinal Macular Pigment

    PubMed Central

    Arteni, Ana-Andreea; Fradot, Mathias; Galzerano, Denise; Mendes-Pinto, Maria M.; Sahel, José-Alain; Picaud, Serge; Robert, Bruno; Pascal, Andrew A.

    2015-01-01

    Human retinal macular pigment (MP) is formed by the carotenoids lutein and zeaxanthin (including the isomer meso-zeaxanthin). MP has several functions in improving visual performance and protecting against the damaging effects of light, and MP levels are used as a proxy for macular health–specifically, to predict the likelihood of developing age-related macular degeneration. While the roles of these carotenoids in retinal health have been the object of intense study in recent years, precise mechanistic details of their protective action remain elusive. We have measured the Raman signals originating from MP carotenoids in ex vivo human retinal tissue, in order to assess their structure and conformation. We show that it is possible to distinguish between lutein and zeaxanthin, by their excitation profile (related to their absorption spectra) and the position of their ν1 Raman mode. In addition, analysis of the ν4 Raman band indicates that these carotenoids are present in a specific, constrained conformation in situ, consistent with their binding to specific proteins as postulated in the literature. We discuss how these conclusions relate to the function of these pigments in macular protection. We also address the possibilities for a more accurate, consistent measurement of MP levels by Raman spectroscopy. PMID:26313550

  9. Macular pigment and lens optical density measurements-evaluating a flicker machine with novel features

    NASA Astrophysics Data System (ADS)

    Mukherjee, Anirbaan

    Age related macular degeneration (AMD) is one of the leading causes of blindness amongst the elderly. Macular pigment (MP) in the retina has been established to protect individuals against AMD. Improving levels of MP by diet or supplements is the constant quest of clinical practitioners and researchers, thus necessitating development of instruments capable of repeatable and reliable MP measurement. Cataract, a consequence of the rising opacity levels of the lens with age is one of the other major causes of blindness in the world. Mapcatsf, a LED-based microprocessor-controlled heterochromatic flicker photometer (HFP) using photopic vision is capable of measuring the levels of MP and the opacity of the lens in terms of optical density. Test-retest measurements conducted on 83 subjects were analyzed for repeatability in macular pigment optical density (MPOD) measurements. Reliability of the lens optical density (LOD) measurements were tested and compared with those obtained at absolute scotopic thresholds for 25 individuals. A supplement study with 32 individuals both in the young (50) age groups for 6 months further established Mapcatsf's capacity to monitor changing levels of MP in individuals. As an overall outcome, high levels of repeatability and reliability were obtained in MPOD and LOD measurements establishing Mapcatsf as an instrument for use in clinical settings in the future.

  10. Macular pigment optical density is related to serum lutein in retinitis pigmentosa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: To determine whether macular pigment optical density (MPOD) is related to the degree of cystoid macular edema (CME) in patients with retinitis pigmentosa. Methods: We measured MPOD with heterochromatic flicker photometry and central foveal retinal thickness with optical coherence tomography...

  11. Temporal Visual Mechanisms May Mediate Compensation for Macular Pigment.

    PubMed

    Stringham, Nicole T; Stringham, James M

    2015-12-01

    Macular pigment (MP) is a pre-receptoral filter that is diet derived and deposited in relatively high optical density in the foveal region of the retina. Due to its yellow coloration, MP absorbs light of relatively short wavelengths, ranging from 400 nm to 520 nm. Despite the spectral and spatial nonuniformity imposed upon the sensory retina by MP, perception appears to be relatively uniform across the central visual field. MP therefore offers an opportunity to determine experimentally potential mechanisms responsible for mediating this uniformity. After assessing, in 14 subjects, MP's effects on the temporal sensitivity of both the short-wavelength- and middle-/long-wavelength-sensitive visual pathways, it appears that the visual system compensates for absorption of short-wavelength light by MP by slowing the sampling rate of short-wavelength cones and by increasing the processing speed of middle-/long-wavelength-sensitive cones. This mechanism could work via temporal summation or a temporal neural code, whereby slower response dynamics lead to amplification of relatively weak signals. PMID:26562864

  12. Macular pigment spatial distribution effects on glare disability

    PubMed Central

    Putnam, Christopher M.; Bassi, Carl J.

    2015-01-01

    Purpose This project explored the relationship of the macular pigment optical density (MPOD) spatial profile with measures of glare disability (GD) across the macula. Methods A novel device was used to measure MPOD across the central 16° of retina along four radii using customized heterochromatic flicker photometry (cHFP)at eccentricities of 0°, 2°, 4°, 6° and 8°. MPOD was measured as discrete and integrated values at all measured retinal loci. GD was calculated as a difference in contrast sensitivity (CS) between no glare and glare conditions using identical stimuli presented at the same eccentricities. GD was defined as [(CSNo Glare − CSGlare)/CSNo Glare] in order to isolate the glare attenuation effects of MPOD by controlling for CS variability among the subject sample. Correlations of the discrete and integrated MPOD with GD were compared. Results The cHFP identified reliable MPOD spatial distribution maps demonstrating a 1st-order exponential decay as a function of increasing eccentricity. There was a significant negative correlation between both measures of foveal MPOD and GD using 6 cycles per degree (cpd) and 9 cpd stimuli. Significant correlations were found between corresponding parafoveal MPOD measures and GD at 2 and 4° of eccentricity using 9 cpd stimuli with greater MPOD associated with less glare disability. Conclusions These results are consistent with the glare attenuation effects of MP at higher spatial frequencies and support the hypothesis that discrete and integrated measures of MPOD have similar correlations with glare attenuation effects across the macula. Additionally, peak foveal MPOD appears to influence GD across the macula. PMID:25697374

  13. Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions

    NASA Astrophysics Data System (ADS)

    Sharifzadeh, Mohsen; Bernstein, Paul S.; Gellermann, Werner

    2006-10-01

    We have developed a CCD-camera-based nonmydriatic instrument that detects fluorescence from retinal lipofuscin chromophores ("autofluorescence") as a means to indirectly quantify and spatially image the distribution of macular pigment (MP). The lipofuscin fluorescence intensity is reduced at all retinal locations containing MP, since MP has a competing absorption in the blue-green wavelength region. Projecting a large diameter, 488 nm excitation spot onto the retina, centered on the fovea, but extending into the macular periphery, and comparing lipofuscin fluorescence intensities outside and inside the foveal area, it is possible to spatially map out the distribution of MP. Spectrally selective detection of the lipofuscin fluorescence reveals an important wavelength dependence of the obtainable image contrast and deduced MP optical density levels, showing that it is important to block out interfering fluorescence contributions in the detection setup originating from ocular media such as the lens. Measuring 70 healthy human volunteer subjects with no ocular pathologies, we find widely varying spatial extent of MP, distinctly differing distribution patterns of MP, and strongly differing absolute MP levels among individuals. Our population study suggests that MP imaging based on lipofuscin fluorescence is useful as a relatively simple, objective, and quantitative noninvasive optical technique suitable to rapidly screen MP levels and distributions in healthy humans with undilated pupils.

  14. Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions

    PubMed Central

    Sharifzadeh, Mohsen; Bernstein, Paul S.; Gellermann, Werner

    2011-01-01

    We have developed a CCD-camera-based nonmydriatic instrument that detects fluorescence from retinal lipofuscin chromophores (“autofluorescence”) as a means to indirectly quantify and spatially image the distribution of macular pigment (MP). The lipofuscin fluorescence intensity is reduced at all retinal locations containing MP, since MP has a competing absorption in the blue–green wavelength region. Projecting a large diameter, 488 nm excitation spot onto the retina, centered on the fovea, but extending into the macular periphery, and comparing lipofuscin fluorescence intensities outside and inside the foveal area, it is possible to spatially map out the distribution of MP. Spectrally selective detection of the lipofuscin fluorescence reveals an important wavelength dependence of the obtainable image contrast and deduced MP optical density levels, showing that it is important to block out interfering fluorescence contributions in the detection setup originating from ocular media such as the lens. Measuring 70 healthy human volunteer subjects with no ocular pathologies, we find widely varying spatial extent of MP, distinctly differing distribution patterns of MP, and strongly differing absolute MP levels among individuals. Our population study suggests that MP imaging based on lipofuscin fluorescence is useful as a relatively simple, objective, and quantitative noninvasive optical technique suitable to rapidly screen MP levels and distributions in healthy humans with undilated pupils. PMID:16985523

  15. Absorption of the eye lens and macular pigment derived from the reflectance of cone photoreceptors

    NASA Astrophysics Data System (ADS)

    Zagers, Niels P. A.; van Norren, Dirk

    2004-12-01

    We measured the amplitude of the directional component of the bleached fundus reflectance, the so-called optical Stiles-Crawford effect, as a function of wavelength. The directional reflectance originates from within the outer segments of the photoreceptors. Thus only two anterior absorbers are of importance: macular pigment and the crystalline lens. Analysis of spectra obtained in pseudophakes established that the cone photoreceptors act as spectrally neutral reflectors. The reflectance spectra, expressed in density units, resembled the macular pigment density spectrum. Studying age effects in the lens of normal subjects resulted in a description of the optical density of the lens in terms of a ``young'' and an ``aged'' template. The young template represents the pigment O-β-glucoside of 3-hydroxykynurenine, which dominates the light absorption in young eyes and decreases with age. The aged template represents the pigments accumulating in the lens with age. The total optical density increased with age, but it was lower in the wavelength region 500-650 nm than was previously assumed on the basis of psychophysical studies. Analysis of the spectra also provided precise individual estimates of the optical density of macular pigment. Finally, we observed a decrease in the photoreceptor reflectivity with age, possibly reflecting a degradation of the photoreceptors.

  16. Macular Pigment Imaging in AREDS2 Participants: An Ancillary Study of AREDS2 Subjects Enrolled at the Moran Eye Center

    PubMed Central

    Bernstein, Paul S.; Ahmed, Faisal; Liu, Aihua; Allman, Susan; Sheng, Xiaoming; Sharifzadeh, Mohsen; Ermakov, Igor; Gellermann, Werner

    2012-01-01

    Purpose. Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions. Methods. All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements. Conclusions. Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.) PMID:22879423

  17. In vivo assessment of retinal carotenoids: macular pigment detection techniques and their impact on monitoring pigment status.

    PubMed

    Curran Celentano, Joanne; Burke, Joanne D; Hammond, Billy R

    2002-03-01

    Of the many carotenoids found within human tissue, only the carotenoids within the human retina can be assessed noninvasively at present. Such assessment should eventually provide a more complete understanding of the functional role of retinal lutein (L) and zeaxanthin (Z) (termed macular pigment, MP) in human vision. The emerging data allow for some initial observations. For example, there appears to be wide variation (>factor of 10) in the concentration of MP. Although MP levels have been recorded from nondetectable to 1.20 OD (optical density), the "average" levels, relative to what is possible, appear low. This may be due in part to the low average dietary intake of L and Z in the typical U.S. diet. Nonetheless, individual differences in MP may also be influenced by nondietary factors such as genetics, demographics and lifestyle characteristics. Some evidence indicates that the MP carotenoids may protect the retina and lens, and could improve vision through some optical mechanisms. Consequently, efforts to determine typical MP levels and the factors that influence individual differences in MP density should be continued. PMID:11880588

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

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    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 light-induced 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.

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

    PubMed

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

    2014-09-01

    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

  1. Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with Macular Pigment Optical Density.

    PubMed

    Ma, Le; Liu, Rong; Du, Jun Hui; Liu, Tao; Wu, Shan Shan; Liu, Xiao Hong

    2016-01-01

    The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (rAMD = -0.43, p = 0.06; rhealthy subjects = -0.71, p < 0.001) and blood xanthophyll carotenoids concentration (rAMD = 0.40, p = 0.07; rhealthy subjects = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship. PMID:27420092

  2. Lutein, Zeaxanthin and Meso-zeaxanthin Supplementation Associated with Macular Pigment Optical Density

    PubMed Central

    Ma, Le; Liu, Rong; Du, Jun Hui; Liu, Tao; Wu, Shan Shan; Liu, Xiao Hong

    2016-01-01

    The purpose of this study was to evaluate the effects of lutein, zeaxanthin and meso-zeaxanthin on macular pigment optical density (MPOD) in randomized controlled trials (RCTs) among patients with age-related macular degeneration (AMD) and healthy subjects. Medline, Embase, Web of Science and Cochrane Library databases was searched through May 2016. Meta-analysis was conducted to obtain adjusted weighted mean differences (WMD) for intervention-versus-placebo group about the change of MPOD between baseline and terminal point. Pearson correlation analysis was used to determine the relationship between the changes in MPOD and blood xanthophyll carotenoids or baseline MPOD levels. Twenty RCTs involving 938 AMD patients and 826 healthy subjects were identified. Xanthophyll carotenoids supplementation was associated with significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14). Stratified analysis showed a greater increase in MPOD among trials supplemented and combined with meso-zeaxanthin. Additionally, the changes in MPOD were related with baseline MPOD levels (rAMD = −0.43, p = 0.06; rhealthy subjects = −0.71, p < 0.001) and blood xanthophyll carotenoids concentration (rAMD = 0.40, p = 0.07; rhealthy subjects = 0.33, p = 0.05). This meta-analysis revealed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects with a dose-response relationship. PMID:27420092

  3. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment.

    PubMed

    Nolan, John M; Stack, Jim; O' Donovan, Orla; Loane, Edward; Beatty, Stephen

    2007-01-01

    Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM). This study was undertaken to investigate MP optical density with respect to risk factors for ARM, in 828 healthy subjects from an Irish population. MP optical density was measured psychophysically using heterochromatic flicker photometry, serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed using a validated food-frequency questionnaire. Clinical and personal details were also recorded, with particular attention directed towards risk factors for ARM. We report a statistically significant age-related decline in MP optical density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical density than never smokers and this difference was statistically significant (p<0.01). Subjects with a confirmed family history of ARM had significantly lower levels of MP optical density than subjects with no known family history of disease (p<0.01). For each of these established risk factors, their statistically significant negative association with MP persisted after controlling for the other two, and also after controlling for other potentially confounding variables such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal pathology, and in advance of disease onset, the relative lack of MP seen in association with increasing age, tobacco use and family history of ARM supports the hypothesis that the enhanced risk that these variables represent for ARM may be attributable, at least in part, to a parallel deficiency of macular carotenoids. PMID:17083932

  4. Measurement of macular pigment optical density among healthy Chinese people and patients with early-stage age-related macular degeneration

    PubMed Central

    Ren, Xue-Tao; Gu, Hong; Han, Xu; Zhang, Jun-Yan; Li, Xue; Yang, Xiu-Fen; Xu, Jun; Snellingen, Torkel; Liu, Xi-Pu; Wang, Ning-Li; Liu, Ning-Pu

    2015-01-01

    AIM To measure the macular pigment optical density (MPOD) in healthy Chinese people and patients with early age-related macular degeneration (AMD). METHODS Cross-sectional population based study. Demographic and lifestyle characteristics were ascertained by questionnaire. A food frequency questionnaire was completed for all participants. Participants underwent general physical and ophthalmic examinations and MPOD was measured by heterochromatic flicker photometry. Foveal architecture was measured by optical coherence tomography. RESULTS MPOD of 225 participants (122 healthy and 103 early AMD) was 0.48±0.18. Patients with early AMD (0.52±0.19) tended to have higher MPOD levels than healthy people (0.47±0.17), but the difference was not statistically significant (P=0.06). Participants with carrot or corn oil intake every week tended to have higher levels of MPOD (P=0.002 and 0.008 respectively) while those with corn intake had relatively lower level of MPOD (P=0.01). MPOD increased with the center foveal thickness (P=0.01). CONCLUSION Our findings show that there is no statistically significant association between MPOD and early AMD in the studied population. MPOD is related to center foveal thickness and diets would influence MPOD levels. PMID:26682171

  5. The Effect of Modified Eggs and an Egg-Yolk Based Beverage on Serum Lutein and Zeaxanthin Concentrations and Macular Pigment Optical Density: Results from a Randomized Trial

    PubMed Central

    Kelly, Elton R.; Plat, Jogchum; Haenen, Guido R. M. M.; Kijlstra, Aize; Berendschot, Tos T. J. M.

    2014-01-01

    Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements. Trial Registration ClinicalTrials.gov NCT00527553 PMID:24675775

  6. NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration

    PubMed Central

    Wang, Yujuan; Hanus, Jakub W.; Abu-Asab, Mones S.; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K.; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao

    2016-01-01

    Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. PMID:26760997

  7. NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration.

    PubMed

    Wang, Yujuan; Hanus, Jakub W; Abu-Asab, Mones S; Shen, Defen; Ogilvy, Alexander; Ou, Jingxing; Chu, Xi K; Shi, Guangpu; Li, Wei; Wang, Shusheng; Chan, Chi-Chao

    2016-01-01

    Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. PMID:26760997

  8. Stimulus edge effects in the measurement of macular pigment using heterochromatic flicker photometry

    NASA Astrophysics Data System (ADS)

    Smollon, William E., Jr.; Wooten, Billy R.; Hammond, Billy R.

    2015-11-01

    Heterochromatic flicker photometry (HFP) is the most common technique of measuring macular pigment optical density (MPOD). Some data strongly suggest that HFP samples MPOD specifically at the edge of center-fixated circular stimuli. Other data have led to the conclusion that HFP samples over the entire area of the stimulus. To resolve this disparity, MPOD was measured using HFP and a series of solid discs of varying radii (0.25 to 2.0 deg) and with thin annuli corresponding to the edge of those discs. MPOD assessed with the two methods yielded excellent correspondence and linearity: Y=0.01+0.98X, r=0.96. A second set of experiments showed that if a disc stimulus is adjusted for no-flicker (the standard procedure) and simply reduced in size, no flicker is observed despite the higher level of MPOD in the smaller area. Taken together, these results confirm that MPOD is determined at the edge of the measuring stimulus when using stimulus sizes in the range that is in dispute (up to a radius of 0.75 deg). The basis for this edge effect can be explained by quantitative differences in the spatial-temporal properties of the visual field as a function of angular distance from the fixation point.

  9. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

    PubMed Central

    Ibrahim, Ahmed S.; Mander, Suchreet; Hussein, Khaled A.; Elsherbiny, Nehal M.; Smith, Sylvia B.; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-01-01

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE–photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features. PMID:26885895

  10. Stimulus edge effects in the measurement of macular pigment using heterochromatic flicker photometry.

    PubMed

    Smollon, William E; Wooten, Billy R; Hammond, Billy R

    2015-11-01

    Heterochromatic flicker photometry (HFP) is the most common technique of measuring macular pigment optical density (MPOD). Some data strongly suggest that HFP samples MPOD specifically at the edge of center-fixated circular stimuli. Other data have led to the conclusion that HFP samples over the entire area of the stimulus. To resolve this disparity, MPOD was measured using HFP and a series of solid discs of varying radii (0.25 to 2.0 deg) and with thin annuli corresponding to the edge of those discs. MPOD assessed with the two methods yielded excellent correspondence and linearity: Y=0.01+0.98X , r=0.96. A second set of experiments showed that if a disc stimulus is adjusted for no-flicker (the standard procedure) and simply reduced in size, no flicker is observed despite the higher level of MPOD in the smaller area. Taken together, these results confirm that MPOD is determined at the edge of the measuring stimulus when using stimulus sizes in the range that is in dispute (up to a radius of 0.75 deg). The basis for this edge effect can be explained by quantitative differences in the spatial-temporal properties of the visual field as a function of angular distance from the fixation point. PMID:26562031

  11. [Notalgia paresthetica, "posterior pigmented pruritic patch" and macular amyloidosis. Three stages of a disease].

    PubMed

    Cerroni, L; Kopera, D; Soyer, H P; Kerl, H

    1993-12-01

    We report on nine cases of notalgia paresthetica, a cutaneous condition that has rarely been described in the dermatological literature and is characterized by localized pruritus, burning and hyperesthesia and/or paresthesia on the back. Histological and immunohistochemical studies have not clarified the pathogenesis of this disease. Several factors might be involved in various cases, including increased cutaneous innervation and neuropathy. The so-called posterior pigmented pruritic patch and macular amyloidosis may be considered as progressive evolutional stages of notalgia paresthetica. PMID:8113041

  12. The Effect of BCMO1 Gene Variants on Macular Pigment Optical Density in Young Healthy Caucasians

    PubMed Central

    Kyle-Little, Zachary; Zele, Andrew J.; Morris, C. Phillip; Feigl, Beatrix

    2014-01-01

    Background: Serum lutein (L) and zeaxanthin (Z) positively correlate with macular pigment optical density (MPOD); hence, the latter is a valuable indirect tool for measuring L and Z content in the macula. L and Z have been attributed antioxidant capacity and protection from certain retinal diseases but their uptake within the eye is thought to depend on genetic, age, and environmental factors. In particular, gene variants within beta-carotene monooxygenase (BCMO1) are thought to modulate MPOD in the macula. Objectives: To determine the effect of BCMO1 single nucleotide polymorphisms (SNPs) rs11645428, rs6420424, and rs6564851 on MPOD in a cohort of young healthy participants of Caucasian origin with normal ocular health. Design: In this cohort study, MPOD was assessed in 46 healthy participants (22 male and 24 female) with a mean age of 23.8 ± 4.0 years (range 19–33). The three SNPs, rs11645428, rs6420424, rs6564851 that have established associations with MPOD were determined using MassEXTEND (hME) Sequenom assay. One-way analysis of variance was performed on groups segregated into homozygous and heterozygous BCMO1 genotypes. Correlations between body mass index (BMI), iris color, gender, central retinal thickness (CRT), diet, and MPOD were investigated. Results: Macular pigment optical density neither significantly varied with BCMO1 rs11645428 (F2,41 = 0.70, p = 0.503), rs6420424 (F2,41 = 0.21, p = 0.801) nor rs6464851 homozygous or heterozygous genotypes (F2,41 = 0,13, p = 0.88), in this young healthy cohort. The combination of these three SNPs into triple genotypes based on plasma conversion efficiency did not affect MPOD (F2,41 = 0.07, p = 0.9). There was a significant negative correlation with MPOD and CRT (r = −0.39, p = 0.01) but no significant correlation between BMI, iris color, gender, and MPOD. Conclusion: Our results indicate that macular pigment deposition within the central retina is not dependent on

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

    PubMed

    Cohen, Philip R

    2009-12-01

    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

  14. Macular pigment, photopigments, and melanin: distributions in young subjects determined by four-wavelength reflectometry.

    PubMed

    Bone, Richard A; Brener, Betty; Gibert, Jorge C

    2007-12-01

    We have developed an objective procedure, using a modified retinal camera, to determine macular pigment (MP) optical density distributions in the human retina. Using two multi-band filters, reflectance maps of the retinas of young subjects (<25 years old) were obtained at 460, 528, 610 and 670 nm, without pupil dilation. The log-transformed maps were combined linearly to yield optical density maps of MP, cone and rod photopigments, and melanin. MP optical density and heterochromatic flicker photometry results for 22 subjects were in reasonable agreement. Cone photopigments, like MP, showed similar, well-defined peaks at the fovea, whereas rod photopigment showed a minimum. Melanin was more broadly distributed. PMID:17937965

  15. High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration

    PubMed Central

    Lee, Dong Kyu; Kim, Soon Hyun; You, Yong Sung

    2016-01-01

    Purpose Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. Methods In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. Results The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Conclusions Increasing the dose of bevacizumab in refractory PED may be a possible treatment option. PMID:27478353

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

    PubMed Central

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

    2012-01-01

    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

  17. Effect of Supplemental Lutein and Zeaxanthin on Serum, Macular Pigmentation, and Visual Performance in Patients with Early Age-Related Macular Degeneration

    PubMed Central

    Huang, Yang-Mu; Dou, Hong-Liang; Huang, Fei-Fei; Xu, Xian-Rong; Zou, Zhi-Yong

    2015-01-01

    Purpose. To compare the 2-year effect of multiple doses of lutein/zeaxanthin on serum, macular pigmentation, and visual performance on patients with early age-related macular degeneration (AMD). Methods. In this randomized, double-blinded, and placebo-controlled trial, 112 early AMD patients randomly received either 10 mg lutein, 20 mg lutein, a combination of lutein (10 mg) and zeaxanthin (10 mg), or placebo daily for 2 years. Serum concentration of lutein/zeaxanthin, macular pigment optical density (MPOD), visual functions including best-spectacle corrected visual acuity (BCVA), contrast sensitivity (CS), flash recovery time (FRT), and vision-related quality of life (VFQ25) was quantified. Results. Serum lutein concentration and MPOD significantly increased in all the active treatment groups. Supplementation with 20 mg lutein was the most effective in increasing MPOD and CS at 3 cycles/degree for the first 48 weeks. However, they both significantly increased to the same peak value following supplementation with either 10 mg or 20 mg lutein during the intervention. No statistical changes of BCVA or FRT were observed during the trial. Conclusions. Long-term lutein supplementation could increase serum lutein concentration, MPOD, and visual sensitivities of early AMD patients. 10 mg lutein daily might be an advisable long-term dosage for early AMD treatment. PMID:25815324

  18. Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

    PubMed

    Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye. PMID:23128960

  19. Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration.

    PubMed

    Ye, Fuxiang; Kaneko, Hiroki; Hayashi, Yumi; Takayama, Kei; Hwang, Shiang-Jyi; Nishizawa, Yuji; Kimoto, Reona; Nagasaka, Yosuke; Tsunekawa, Taichi; Matsuura, Toshiyuki; Yasukawa, Tsutomu; Kondo, Takaaki; Terasaki, Hiroko

    2016-05-01

    Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels. PMID:26923802

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

    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.

  1. Women's Health Initiative diet intervention did not increase macular pigment optical density in an ancillary study of a subsample of the Women's Health Initiative.

    PubMed

    Moeller, Suzen M; Voland, Rick; Sarto, Gloria E; Gobel, Vicki L; Streicher, Sharyn L; Mares, Julie A

    2009-09-01

    In this study, we examined the impact of long-term (>8 y), low-fat, high-fruit and -vegetable diets on levels of lutein and zeaxanthin in the macula of the retina, as indicated by the OD of macular pigment. Macular pigment OD, measured by heterochromatic flicker photometry, was compared in women aged 60-87 y, who, 7-18 mo earlier (median 12 mo), had been in the dietary modification intervention (n = 158) or comparison (n = 236) groups of the Women's Health Initiative (WHI) at the Madison, WI site for a mean of 8.5 y. Women in the intervention group ate more fruits and vegetables (mean +/- SEM) (6.1 +/- 0.2 vs. 4.6 +/- 0.2 servings/d; P < 0.0001) and had higher intakes of lutein and zeaxanthin from foods and supplements (2.7 +/- 0.2 vs. 2.1 +/- 0.1 mg/d; P = 0.0003) than the comparison group. However, macular pigment density did not differ between the intervention (0.36 +/- 0.02 OD units) and comparison (0.35 +/- 0.01 OD units) groups. It tended to be higher (11%; P = 0.11) in women consuming lutein and zeaxanthin in the highest compared with the lowest quintile (median 6.4 vs. 1.1 mg/d). The increase in fruit and vegetable intake among dietary modification participants of this WHI subsample was not of sufficient magnitude to alter the mean density of retinal carotenoids, given other existing dietary conditions in this sample. PMID:19587126

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    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 μm (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.

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

    PubMed Central

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

    2011-01-01

    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 μm (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

  4. 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

    2014-01-01

    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 < 0.0001 and p = 0.001, respectively) were higher in older vs younger subjects, whereas macular pigment optical density was lower (p = 0.038). The highest correlation coefficients between intake and serum were for fruit and serum lutein (ρ = 0.452, p < 0.0001) and for fruit and lutein + zeaxanthin (ρ = 0.431, p < 0.0001) in the younger group. Macular pigment optical density correlated with serum xanthophylls (ρ = 0.223, p = 0.02) and fruit and vegetable intake (ρ = 0.350, p = 0.0002), showing highest correlations when lutein and zeaxanthin were expressed in relation to serum lipids in older subjects (ρ = 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

  5. The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration.

    PubMed

    Stringham, J M; Hammond, B R; Nolan, J M; Wooten, B R; Mammen, A; Smollon, W; Snodderly, D M

    2008-11-01

    The purpose of this study was to assess the utility and validity of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment optical density (MPOD) in patients with intermediate stages of age-related macular degeneration (AMD). The measurement procedure was optimized to accommodate individual differences in temporal vision related to age, disease, or other factors. The validity criteria were based on the similarity of the spectral absorption curves to ex vivo curves of lutein and zeaxanthin and the similarity of spatial density profiles to those measured in subjects without retinal disease. Macular pigment optical density (MPOD) spatial profiles were measured with an LED-based macular densitometer; spectral absorption curves were measured with a 3-channel Maxwellian view system including a monochromator. All patients were characterized via clinical exams and all but 2 subjects from whom data were obtained had masked grading of color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. Most of the patients were in AREDS category 2 (27%) or 3 (57%). Patients with visual acuity as poor as 20/80 were included, and could perform the task as long as they could see the stimulus. Eighty-one percent of the patients screened were able to perform the cHFP task, and data were obtained from 30 AMD patients. Spatial profiles of MPOD were measured in 19 subjects who could see the stimulus at all tested loci. These profiles were highly similar to those that have been measured with HFP in subjects without retinal disease. The average shape of the spectral absorption curves for the AMD subjects corresponded well to an ex vivo template. These data support both the utility and validity of the cHFP method for measuring MPOD in subjects with intermediate stages of AMD. The ability to measure the retinal response to nutritional intervention is of practical importance for monitoring patients being supplemented with lutein and

  6. Macular Pigment Optical Density in the Elderly: Findings in a Large Biracial Midsouth Population Sample

    PubMed Central

    Iannaccone, Alessandro; Mura, Marco; Gallaher, Kevin T.; Johnson, Elizabeth J.; Todd, William Andrew; Kenyon, Emily; Harris, Tarsha L.; Harris, Tamara; Satterfield, Suzanne; Johnson, Karen C.; Kritchevsky, Stephen B.

    2008-01-01

    Purpose To report the macular pigment optical density (MPOD) findings at 0.5° of eccentricity from the fovea in elderly subjects participating in ARMA, a study of aging and age-related maculopathy (ARM) ancillary to the Health, Aging, and Body Composition (Health ABC) Study. Methods MPOD was estimated with a heterochromatic flicker photometry (HFP) method in a large biracial population sample of normal 79.1 ± 3.2-year-old adults living in the Midsouth (n = 222; 52% female; 23% black, 34% users of lutein-containing supplements). Within a modified testing protocol, subjects identified the lowest and the highest target intensity at which the flicker sensation disappeared, and the exact middle of this “no-flicker zone” was interpolated by the examiner. Results An MPOD estimate was obtained successfully in 82% of the participants. The mean MPOD in our sample was 0.34 ± 0.21 (SD). The interocular correlation was high (Pearson’s r = 0.82). Compared with lutein supplement users, mean MPOD was 21% lower in nonusers (P = 0.013). MPOD was also 41% lower in blacks than in whites (P = 0.0002), even after adjustment for lutein supplement use. There were no differences in MPOD by gender, iris color, or history of smoking. Conclusions Older adults in the Midsouth appear to have average MPOD and interocular correlation comparable to those in previous studies. Lutein supplement use and white race correlated with higher MPOD. No evidence of an age-related decline in MPOD was seen in the sample. The HFP method for the measurement of MPOD is feasible in epidemiologic investigations of the elderly, the group at highest risk of ARM. PMID:17389471

  7. Progression of Retinal Pigment Epithelial Atrophy in Antiangiogenic Therapy of Neovascular Age-Related Macular Degeneration

    PubMed Central

    Schütze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K.; Schmidt-Erfurth, Ursula

    2015-01-01

    Purpose To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Design Prospective interventional case series. Methods setting: Clinical practice. study population: Thirty patients (31 eyes) with treatment-naïve neovascular AMD. observation procedures: Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. main outcome measures: RPE response, geographic atrophy (GA) progression. Results Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm2 at 12 months to 1.10 mm2 (standard deviation = 1.09 mm2) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Conclusions Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. PMID:25769245

  8. Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements

    PubMed Central

    Okazaki, Shigetoshi; Gellermann, Werner; Bernstein, Paul S.

    2015-01-01

    Purpose To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. Methods Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. Results The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. “retinal responders”, who had an increase of both MPOD levels and serum lutein concentrations (n = 13), “retinal non-responders”, who had only increased serum concentrations and no change in MPOD levels (n = 20), and “retinal and serum non-responders”, who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in

  9. Phototoxic Action Spectrum on a Retinal Pigment Epithelium Model of Age-Related Macular Degeneration Exposed to Sunlight Normalized Conditions

    PubMed Central

    Arnault, Emilie; Barrau, Coralie; Nanteau, Céline; Gondouin, Pauline; Bigot, Karine; Viénot, Françoise; Gutman, Emmanuel; Fontaine, Valérie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, José-Alain; Picaud, Serge

    2013-01-01

    Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the

  10. Spatial Mapping of Macular Pigment Optical Density and Its Relationship to Contrast Sensitivity and Glare Disability

    NASA Astrophysics Data System (ADS)

    Putnam, Christopher

    This dissertation explored the relationship of the macular pigment optical density (MPOD) spatial profile with measures of contrast sensitivity (CS), glare disability (GD), relative glare disability (RGD) and intraocular light scatter. A novel device capable of measuring MPOD across the central 160 of retina along 8 principle meridians using customized heterochromatic flicker photometry (cHFP) at eccentricities of 00, 20, 40, 60 and 80 was built. MPOD was calculated as both discrete and integrated values at all measured retinal loci. CS was measured using vertical grating stimuli of 3, 6 and 9 cycles per degree (cpd) also presented at 00, 20, 4 0, 60 and 80 eccentricity. GD was calculated as a difference in CS between glare and no glare conditions (CSNo Glare - CSGlare) using the same vertical grating stimuli presented at the same eccentricities. RGD [(CSNo Glare - CSGlare) / CSNo Glare] was calculated to isolate the glare attenuation effects of MPOD by controlling for CS variability among the subject sample. Intraocular scatter was assessed through a direct compensation method using a commercially available device. Statistical analyses of the discrete and integrated MPOD associations with CS, GD, RGD and intraocular scatter were evaluated. The cHFP identified reliable MPOD spatial distribution maps demonstrating a 1 st order exponential decay curve as a function of increasing eccentricity. Foveal MPOD revealed the highest correlation coefficients with RGD using 9cpd stimuli. These results are consistent with the glare attenuation effects of MP at higher spatial frequencies. Further support may be seen from the significant correlations found between corresponding parafoveal MPOD measures and both GD and RGD at 20 and 40 of eccentricity using 9cpd stimuli with greater MPOD being associated with less glare disability. All calculated measures of foveal MPOD shared similar significant correlation coefficients with both GD and RGD using 6cpd and 9cpd stimuli. Discrete

  11. Macular pigment optical density: repeatability, intereye correlation, and effect of ocular dominance

    PubMed Central

    Davey, Pinakin Gunvant; Alvarez, Silverio D; Lee, Jessica Y

    2016-01-01

    Purpose To evaluate short-term repeatability, intereye correlation, and effect of ocular dominance on macular pigment optical density (MPOD) measurements obtained using the QuantifEye Heterochromatic Flicker Photometer. Patients and methods A total of 72 study participants were enrolled in this prospective, cross-sectional study. Participants underwent a comprehensive ocular evaluation, including visual acuity, evaluation of ocular dominance, slit lamp examination, intraocular pressure measurement, and optic nerve head and macula analysis using optical coherence tomography and fundus photography. All study participants after initial training underwent MPOD measurement twice in both eyes in a randomized sequence. The repeatability was tested using Altman and Bland plots for first measurements with the second measurements for right eye and left eye and additionally by grouping eyes as a function of ocular dominance. The Pearson correlation coefficient was performed to assess the intereye correlation of MPOD values. Results The mean age of study participants was 35.5 years (range 22–68 years). The mean MPOD measurements for OD (right eye) and OS (left eye) were 0.47 and 0.48, respectively, which followed a normal distribution (Shapiro–Wilk test, P=0.6 and 0.2). The 95% limits of agreement of Altman and Bland plots for the first and second measurements were −0.12 to +0.11 and −0.13 to +0.12 for OD and OS, respectively. The correlation coefficient of mean MPOD measurements of OD and OS was r statistic =0.94 (Pearson correlation coefficient P<0.0001; r2 0.89). The 95% limits of agreement of Altman and Bland plots when evaluated by laterality of eye or by ocular dominance were narrow, with limits of agreement ranging from −0.13 to +0.12. Conclusion The MPOD measurements obtained using the QuantifEye show good short-term repeatability. There is excellent intereye correlation, indicating that the MPOD values of one eye data can predict the fellow eye value with 89

  12. Vitreous estrogen levels in patients with an idiopathic macular hole

    PubMed Central

    Inokuchi, Naoki; Ikeda, Tsunehiko; Nakamura, Kimitoshi; Morishita, Seita; Fukumoto, Masanori; Kida, Teruyo; Oku, Hidehiro

    2015-01-01

    Purpose Estrogen, a female hormone, activates collagenase and might be associated with the pathogenesis of vitreoretinal collagen fiber disease. The purpose of the present study was to investigate the vitreous levels of estrone (E1) and estradiol (E2) in subjects with an idiopathic macular hole (IMH). Methods Vitreous samples were obtained from ten female patients with an IMH and from nine female patients with other retinal diseases (six with rhegmatogenous retinal detachment and three with age-related macular degeneration) as a control at the time of vitreous surgery. E1 and E2 levels in the vitreous samples were then determined using the Coat-A-Count® Estradiol Radioimmunoassay (RIA) Kit and the DSL-70 Estrone RIA Kit, respectively. Results The mean vitreous levels of E1 and E2 in the subjects with IMH were 1.83±2.00 pg/mL and 7.03±2.97 pg/mL, respectively, whereas in the control subjects they were 2.42±1.25 pg/mL and 4.90±2.90 pg/mL, respectively. Thus, the vitreous E2 levels in the subjects with IMH were significantly higher than in the controls (P<0.05). Conclusion The findings of this study suggest that E2 might be associated with the pathogenesis of IMH, but further investigation is needed to elucidate that association. PMID:25848205

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

    PubMed Central

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

    2013-01-01

    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

  14. Macular Pigment Optical Density in Chinese Primary Open Angle Glaucoma Using the One-Wavelength Reflectometry Method

    PubMed Central

    Ji, Yuying; Zuo, Chengguo; Lin, Mingkai; Zhang, Xiongze; Li, Miaoling; Mi, Lan; Liu, Bing; Wen, Feng

    2016-01-01

    Purpose. To investigate macular pigment optical density (MPOD) and its relationship with retinal thickness in primary open angle glaucoma (POAG) patients using the one-wavelength reflectometry method. Methods. A total of 30 eyes from 30 POAG patients (18 males and 12 females, mean age 47.27 ± 16.93) and 52 eyes from 52 controls (27 males and 25 females, mean age 49.54 ± 19.15) were included in this prospective, observational, case-control study. MPOD was measured in a 7-degree area using one-wavelength reflectometry method. Two parameters, max and mean optical density (OD), were used for analyses. Spectral-domain-optical coherence tomography was used to measure retinal thickness, including central retinal thickness (CRT), the macular ganglion cell complex (GCC), and the circumpapillary retinal nerve fiber layer (RNFL). Results. Both maxOD and meanOD were significantly reduced in POAG patients compared with normal subjects (P < 0.001). GCC, CRT, and RNFL thicknesses were also significantly reduced in POAG patients (P < 0.001). GCC thickness had a positive relationship with MPOD. Conclusions. MPOD within the 7-degree area was significantly lower in Chinese POAG patients than in control subjects, and GCC thickness was significantly and positively associated with MPOD. Whether the observed lower MPOD in POAG contributes to the disease process or is secondary to pathological changes caused by the disease (such as loss of ganglion cells) warrants further and longitudinal study. PMID:27144013

  15. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients.

    PubMed

    Song, Won Kyung; Park, Kyung-Mi; Kim, Hyun-Ju; Lee, Jae Ho; Choi, Jinjung; Chong, So Young; Shim, Sung Han; Del Priore, Lucian V; Lanza, Robert

    2015-05-12

    Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease. Here, we report the safety and tolerability of subretinal transplantation of human embryonic-stem-cell (hESC)-derived retinal pigment epithelium in four Asian patients: two with dry age-related macular degeneration and two with Stargardt macular dystrophy. They were followed for 1 year. There was no evidence of adverse proliferation, tumorigenicity, ectopic tissue formation, or other serious safety issues related to the transplanted cells. Visual acuity improved 9-19 letters in three patients and remained stable (+1 letter) in one patient. The results confirmed that hESC-derived cells could serve as a potentially safe new source for regenerative medicine. PMID:25937371

  16. Resonant imaging of carotenoid pigments in the human retina

    NASA Astrophysics Data System (ADS)

    Gellermann, Werner; Emakov, Igor V.; McClane, Robert W.

    2002-06-01

    We have generated high spatial resolution images showing the distribution of carotenoid macular pigments in the human retina using Raman spectroscopy. A low level of macular pigments is associated with an increased risk of developing age-related macular degeneration, a leading cause of irreversible blindness. Using excised human eyecups and resonant excitation of the pigment molecules with narrow bandwidth blue light from a mercury arc lamp, we record Raman images originating from the carbon-carbon double bond stretch vibrations of lutein and zeaxanthin, the carotenoids comprising human macular pigments. Our Raman images reveal significant differences among subjects, both in regard to absolute levels as well as spatial distribution within the macula. Since the light levels used to obtain these images are well below established safety limits, this technique holds promise for developing a rapid screening diagnostic in large populations at risk for vision loss from age-related macular degeneration.

  17. The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

    PubMed Central

    Zanzottera, Emma C.; Messinger, Jeffrey D.; Ach, Thomas; Smith, R. Theodore; Freund, K. Bailey; Curcio, Christine A.

    2015-01-01

    Purpose. To seek pathways of retinal pigment epithelium (RPE) fate in age-related macular degeneration via a morphology grading system; provide nomenclature, visualization targets, and metrics for clinical imaging and model systems. Methods. Donor eyes with geographic atrophy (GA) or choroidal neovascularization (CNV) and one GA eye with previous clinical spectral-domain optical coherence tomography (SDOCT) imaging were processed for histology, photodocumented, and annotated at predefined locations. Retinal pigment epithelial cells contained spindle-shaped melanosomes, apposed a basal lamina or basal laminar deposit (BLamD), and exhibited recognizable morphologies. Thicknesses and unbiased estimates of frequencies were obtained. Results. In 13 GA eyes (449 locations), ‘Shedding,’ ‘Sloughed,’ and ‘Dissociated’ morphologies were abundant; 22.2% of atrophic locations had ‘Dissociated’ RPE. In 39 CNV eyes (1363 locations), 37.3% of locations with fibrovascular/fibrocellular scar had ‘Entombed’ RPE; ‘Sloughed,’ ‘Dissociated,’ and ‘Bilaminar’ morphologies were abundant. Of abnormal RPE, CNV and GA both had ∼35% ‘Sloughed’/‘Intraretinal,’ with more Intraretinal in CNV (9.5% vs. 1.8%). ‘Shedding’ cells associated with granule aggregations in BLamD. The RPE layer did not thin, and BLamD remained thick, with progression. Granule-containing material consistent with three morphologies correlated to SDOCT hyperreflective foci in the previously examined GA patient. Conclusions. Retinal pigment epithelium morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are ‘Dissociated’ and ‘Sloughed’ cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping

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

    NASA Astrophysics Data System (ADS)

    Vishwanathan, Rohini

    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 macular degeneration (AMD), the leading cause of vision loss in the elderly population. Antioxidant and lutein supplementation has been shown to decrease the risk and prevent the progression of AMD. The egg yolk is a highly bioavailable source of lutein and zeaxanthin and thus a possible contender for AMD prevention and treatment. Consumption of 2 egg yolks/d for 5 weeks was shown herein to significantly increase serum lutein and zeaxanthin concentration and clinically improve macular pigment concentrations at 0.5° retinal eccentricity in an older adult population taking cholesterol-lowering statins. Four egg yolks/d not only raised serum lutein and zeaxanthin significantly but also macular pigment densities at 0.25°, 0.5° and 1° retinal eccentricity. A positive outcome of the 2 egg yolk consumption was the significant increase in serum HDL-C with a tendency of serum LDL-C to decrease, although not significantly. Four egg yolks/d seemed to cross the threshold for dietary cholesterol tolerance as serum LDL-C tended to increase, although not significantly, despite the significant increase in serum HDL-C. There is a strong possibility that greater build up of lutein and zeaxanthin in the macula may have been observed with 2 egg yolks/d if the intervention period was longer than 5 weeks. Addition of up to 2 eggs a day to the diet is suggested to benefit an older adult population, especially those who are already taking cholesterol-lowering statins by (a) building their macular pigment and possibly protect against AMD and (b

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

    NASA Astrophysics Data System (ADS)

    Vishwanathan, Rohini

    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 macular degeneration (AMD), the leading cause of vision loss in the elderly population. Antioxidant and lutein supplementation has been shown to decrease the risk and prevent the progression of AMD. The egg yolk is a highly bioavailable source of lutein and zeaxanthin and thus a possible contender for AMD prevention and treatment. Consumption of 2 egg yolks/d for 5 weeks was shown herein to significantly increase serum lutein and zeaxanthin concentration and clinically improve macular pigment concentrations at 0.5° retinal eccentricity in an older adult population taking cholesterol-lowering statins. Four egg yolks/d not only raised serum lutein and zeaxanthin significantly but also macular pigment densities at 0.25°, 0.5° and 1° retinal eccentricity. A positive outcome of the 2 egg yolk consumption was the significant increase in serum HDL-C with a tendency of serum LDL-C to decrease, although not significantly. Four egg yolks/d seemed to cross the threshold for dietary cholesterol tolerance as serum LDL-C tended to increase, although not significantly, despite the significant increase in serum HDL-C. There is a strong possibility that greater build up of lutein and zeaxanthin in the macula may have been observed with 2 egg yolks/d if the intervention period was longer than 5 weeks. Addition of up to 2 eggs a day to the diet is suggested to benefit an older adult population, especially those who are already taking cholesterol-lowering statins by (a) building their macular pigment and possibly protect against AMD and (b

  20. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    PubMed Central

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE. Methods We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE. Results We defined sets of mouse (64), human (171) and mouse–human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like “organ development” and “disorders related to neurological tissue”. However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch’s membrane, immune-regulation and outer blood retina barrier. Conclusion These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular

  1. Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

    PubMed Central

    Zhao, Chun; Zhang, Zhen; Chen, Lei; Wang, Fang; Xu, Ding

    2016-01-01

    Background We sought to observe the effectiveness of intravitreal injection of ranibizumab in treating neovascular age-related macular degeneration (nAMD) with serous pigment epithelial detachment (sPED). Material/Methods A retrospective, noncomparative case series was performed. Twenty-3 eyes of 23 patients with sPED secondary to nAMD who had received intravitreal injections of ranibizumab were included in this study. All patients underwent best-corrected visual acuity (BCVA), synchronous fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) examinations. All patients were treated with pro re nata intravitreal injections after 3 loading doses of ranibizumab and were followed up for 12 months. The differences in the BCVAs, maximum PED heights, PED volumes and CFTs of the affected eyes were compared between the baseline and last visit. Results Twelve months after the first injection, improved visual acuity was observed in 16 of the 23 eyes. 4 eyes exhibited stable visual acuity, and 3 eyes exhibited impaired visual acuity. The mean post-injection logMAR BCVA was 0.58±0.05, which was much better than that at baseline (0.76±0.08; t=1.751, P=0.0869). The mean maximum PED height at baseline was 350.17±35.73μm and it was decreased to 238.87±36.87μm (t=2.192, P=0.0337) at the last visit. The mean PED volume after injection was 0.34±0.1 mm3, which was significantly decreased compared with that at baseline (0.81±0.21 mm3; t=2.021, P=0.0494).The mean CFT decreased, but this difference was not statistically significant (t=1.003, P=0.3211). None of the patients exhibited endophthalmitis, uveitis or RPE tears. Conclusions Intravitreal injection of ranibizumab for the treatment of neovascular age-related macular degeneration with serous pigment epithelial detachment safely and effectively improved the patients’ visual acuities and decreased their PED heights volumes. PMID:26972376

  2. Lipofuscin Redistribution and Loss Accompanied by Cytoskeletal Stress in Retinal Pigment Epithelium of Eyes With Age-Related Macular Degeneration

    PubMed Central

    Ach, Thomas; Tolstik, Elen; Messinger, Jeffrey D.; Zarubina, Anna V.; Heintzmann, Rainer; Curcio, Christine A.

    2015-01-01

    Purpose. Lipofuscin (LF) and melanolipofuscin (MLF) of the retinal pigment epithelium (RPE) are the principal sources of autofluorescence (AF) signals in clinical fundus–AF imaging. Few details about the subcellular distribution of AF organelles in AMD are available. We describe the impact of aging and AMD on RPE morphology revealed by the distribution of AF LF/MLF granules and actin cytoskeleton in human tissues. Methods. Thirty-five RPE-Bruch's membrane flatmounts from 35 donors were prepared (postmortem: ≤4 hours). Ex vivo fundus examination at the time of accession revealed either absence of chorioretinal pathologies (10 tissues; mean age: 83.0 ± 2.6 years) or stages of AMD (25 tissues; 85.0 ± 5.8 years): early AMD, geographic atrophy, and late exudative AMD. Retinal pigment epithelium cytoskeleton was labeled with AlexaFluor647-Phalloidin. Tissues were imaged on a spinning-disk fluorescence microscope and a high-resolution structured illumination microscope. Results. Age-related macular degeneration impacts individual RPE cells by (1) lipofuscin redistribution by (i) degranulation (granule-by-granule loss) and/or (ii) aggregation and apparent shedding into the extracellular space; (2) enlarged RPE cell area and conversion from convex to irregular and sometimes concave polygons; and (3) cytoskeleton derangement including separations and breaks around subretinal deposits, thickening, and stress fibers. Conclusions. We report an extensive and systematic en face analysis of LF/MLF-AF in AMD eyes. Redistribution and loss of AF granules are among the earliest AMD changes and could reduce fundus AF signal attributable to RPE at these locations. Data can enhance the interpretation of clinical fundus–AF and provide a basis for future quantitative studies. PMID:25758814

  3. Non-responsiveness to intravitreal aflibercept treatment in neovascular age-related macular degeneration: implications of serous pigment epithelial detachment

    PubMed Central

    Nagai, Norihiro; Suzuki, Misa; Uchida, Atsuro; Kurihara, Toshihide; Kamoshita, Mamoru; Minami, Sakiko; Shinoda, Hajime; Tsubota, Kazuo; Ozawa, Yoko

    2016-01-01

    The prognosis of neovascular age-related macular degeneration (AMD) has been improved by anti-vascular endothelial growth factor treatments, including intravitreal aflibercept (IVA) treatment. However, many patients remain incurable. In this study, we retrospectively evaluated non-responsiveness to IVA monotherapy at 12 months in 133 eyes of 133 AMD patients. Sixty-two patients were initially treatment-naive, and 71 had received other treatments before IVA (the treatment-switched group). Mean best-corrected visual acuity (BCVA) was improved in the treatment-naive group but not in the treatment-switched group, although mean central retinal thickness (CRT) decreased in both groups. The respective percentages of non-responders as determined by worsened BCVA in the treatment-naive and treatment-switched groups were 8.1% and 15.5%, and via fundus findings, they were 12.9% and 8.5%. Multivariate analyses adjusted for age, gender, CRT, and greatest linear dimension showed that serous pigment epithelial detachment (PED) at baseline was associated with non-responsiveness in both groups as determined by BCVA and by fundus findings, and fibrovascular PED measurements indicated no response as determined by fundus findings in the treatment-switched group. The results reported herein may assist the formulation of appropriate treatment protocols for AMD patients. PMID:27403807

  4. Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles

    NASA Astrophysics Data System (ADS)

    van der Veen, Rob L. P.; Berendschot, Tos T. J. M.; Makridaki, Maria; Hendrikse, Fred; Carden, David; Murray, Ian J.

    2009-11-01

    A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg.

  5. Macular telangiectasia type 2

    PubMed Central

    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

    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

  6. Macular telangiectasia type 2.

    PubMed

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

    2013-05-01

    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 non-neovascular 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

  7. Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids

    PubMed Central

    Kelly, David; Coen, Robert F.; Akuffo, Kwadwo Owusu; Beatty, Stephen; Dennison, Jessica; Moran, Rachel; Stack, Jim; Howard, Alan N.; Mulcahy, Riona; Nolan, John M.

    2015-01-01

    Abstract Background: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly. Objective: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n = 105) and in subjects with AMD (Group 2, n = 121). Methods: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC. Results: Significant correlations were evident between MP and various measures of cognitive function in both groups (r = –0.273 to 0.261, p≤0.05, for all). Both serum L and Z concentrations correlated significantly (r = 0.187, p≤0.05 and r = 0.197, p≤0.05, respectively) with semantic (animal) fluency cognitive scores in Group 2 (the AMD study group), while serum L concentrations also correlated significantly with Verbal Recognition Memory learning slope scores in the AMD study group (r = 0.200, p = 0.031). Most of the correlations with MP, but not serum L or Z, remained significant after controlling for age, gender, diet, and education level. Conclusion: MP offers potential as a non-invasive clinical biomarker of cognitive health, and appears more successful in this role than serum concentrations of L or Z. PMID:26401946

  8. [Tear in retinal pigment epithelium under anti-VEGF therapy for exudative age-related macular degeneration : function recovery under intensive therapy].

    PubMed

    Bartels, S; Barrelmann, A; Book, B; Heimes, B; Gutfleisch, M; Spital, G; Pauleikhoff, D; Lommatzsch, A

    2014-05-01

    This article reports the case of a 72-year-old woman with pigment epithelial detachment with occult choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) which developed under anti-vascular endothelial growth factor (VEGF) therapy of a tear in the retinal pigment epithelium (RPE). In the area of free RPE autofluorescence was completely absent and the microperimetry in this area showed an absolute scotoma. The visual acuity was 0.1. After continuation of anti-VEGF therapy because of persistent subretinal and intraretinal fluid over 3 years an increased autofluorescence was observed and the microperimetry showed an increase in central retinal sensitivity. The central visual acuity improved to 0.5 and in this area a whitish subretinal tissue formed morphologically. In the spectral domain optical coherence tomography (SD-OCT) image this structure was hyperreflective which might suggest a certain regeneration process of the RPE under anti-VEGF-therapy. PMID:24046170

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

    PubMed Central

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

    2000-01-01

    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, encoding the protein bestrophin, was identified. The function of bestrophin is unknown. To facilitate studies of bestrophin, we produced both rabbit polyclonal and mouse monoclonal antibodies that proved useful for Western blotting, immunoprecipitation, and immunocytochemistry. To characterize bestrophin, we initially probed the retinal pigment epithelium (RPE)-derived cell lines ARPE-19, D407, and RPE-J. All of the cell lines expressed bestrophin mRNA by reverse transcription-PCR, but not on Western blots. Bestrophin in human RPE partitioned in the detergent phase during Triton X-114 extraction and could be modified by biotin in intact cells, indicative of a plasma membrane localization. Immunocytochemical staining of macaque and porcine eyes indicated that bestrophin is localized at the basolateral plasma membrane of RPE cells. When expressed in RPE-J cells by adenovirus-mediated gene transfer, bestrophin again was determined by confocal microscopy and cell surface biotinylation to be a basolateral plasma membrane protein. The basolateral plasma membrane localization of bestrophin suggests the possibility that bestrophin plays a role in generating the altered electrooculogram of individuals with Best disease. PMID:11050159

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

    PubMed

    Marmorstein, A D; Marmorstein, L Y; Rayborn, M; Wang, X; Hollyfield, J G; Petrukhin, K

    2000-11-01

    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, encoding the protein bestrophin, was identified. The function of bestrophin is unknown. To facilitate studies of bestrophin, we produced both rabbit polyclonal and mouse monoclonal antibodies that proved useful for Western blotting, immunoprecipitation, and immunocytochemistry. To characterize bestrophin, we initially probed the retinal pigment epithelium (RPE)-derived cell lines ARPE-19, D407, and RPE-J. All of the cell lines expressed bestrophin mRNA by reverse transcription-PCR, but not on Western blots. Bestrophin in human RPE partitioned in the detergent phase during Triton X-114 extraction and could be modified by biotin in intact cells, indicative of a plasma membrane localization. Immunocytochemical staining of macaque and porcine eyes indicated that bestrophin is localized at the basolateral plasma membrane of RPE cells. When expressed in RPE-J cells by adenovirus-mediated gene transfer, bestrophin again was determined by confocal microscopy and cell surface biotinylation to be a basolateral plasma membrane protein. The basolateral plasma membrane localization of bestrophin suggests the possibility that bestrophin plays a role in generating the altered electrooculogram of individuals with Best disease. PMID:11050159

  11. 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 Central

    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

    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

  12. 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)

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

    2002-10-01

    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.

  13. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

    PubMed Central

    Bhutto, Imran A.; McLeod, D. Scott; Hasegawa, Takuya; Kim, Sahng Y.; Merges, Carol; Tong, Patrick; Lutty, Gerard A.

    2016-01-01

    The purpose of this study was to examine the localization and relative levels of vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid and to determine if the localization or their relative levels changed in age-related macular degeneration (AMD). Ocular tissues were obtained from eight aged control donors (age range, 75–86 years; mean age, 79.8 years) with no evidence or history of chorioretinal disease and from 12 donors diagnosed with AMD (age range, 61–105 years; mean age, 83.9 years). Tissues were cryopreserved and streptavidin alkaline phosphatase immunohistochemistry was performed with rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF antibodies. Binding of the antibodies was blocked by preincubation of the antibody with an excess of recombinant human PEDF or VEGF peptide. Choroidal blood vessels were identified with mouse anti-human CD-34 antibody in adjacent tissue sections. Three independent observers graded the immunohistochemical reaction product. The most prominent sites of VEGF and PEDF localization in aged control choroid were RPE–Bruch’s membrane–choriocapillaris complex including RPE basal lamina, intercapillary septa, and choroidal stroma. There was no significant difference in immunostaining intensity and localization of VEGF and PEDF in aged control choroids. The most intense VEGF immunoreactivity was observed in leukocytes within blood vessels. AMD choroid had a similar pattern and intensity of VEGF immunostaining to that observed in aged controls. However, PEDF immunoreactivity was significantly lower in RPE cells (p = 0.0073), RPE basal lamina (p = 0.0141), Bruch’s membrane (p < 0.0001), and choroidal stroma (p = 0.0161) of AMD choroids. The most intense PEDF immunoreactivity was observed in disciform scars. Drusen and basal laminar deposits (BLDs) were positive for VEGF and PEDF. In aged control subjects

  14. Estimation of macular pigment optical density in the elderly: Test–retest variability and effect of optical blur in pseudophakic subjects

    PubMed Central

    Gallaher, Kevin T.; Mura, Marco; Todd, Wm. Andrew; Harris, Tarsha L.; Kenyon, Emily; Harris, Tamara; Johnson, Karen C.; Satterfield, Suzanne; Kritchevsky, Stephen B.; Iannaccone, Alessandro

    2008-01-01

    The reproducibility of macular pigment optical density (MPOD) estimates in the elderly was assessed in 40 subjects (age: 79.1 ± 3.5). Test–retest variability was good (Pearson’s r coefficient: 0.734), with an average coefficient of variation (CV) of 18.4% and an intraclass correlation coefficient (ICC) of 0.96. The effect of optical blur on MPOD estimates was investigated in 22 elderly pseudophakic subjects (age: 79.9 ± 3.6) by comparing the baseline MPOD, obtained with an optimal correction, with MPODs obtained with a ±1.00-diopter optical blur. This optical blur did not cause differences in the MPOD estimates, its accuracy, or test duration. PMID:17376502

  15. Three dimensional distribution of the vitelliform lesion, photoreceptors, and retinal pigment epithelium in the macula of patients with Best vitelliform macular dystrophy

    PubMed Central

    Kay, Christine N.; Abramoff, Michael D.; Mullins, Robert F.; Kinnick, Tyson R.; Lee, Kyuongmoo; Eyestone, Mari E.; Chung, Mina M.; Sohn, Elliott H.; Stone, Edwin M.

    2015-01-01

    Objective To describe the anatomical phenotypes of Best vitelliform macular dystrophy (BVMD) with spectraldomain optical coherence tomography (SD-OCT) in a large series of patients with confirmed mutations in the BEST1 gene. Methods In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis. Results The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 μm, and control patients had a mean photoreceptor equivalent thickness of 21.8 μm, a mean difference of 6.5 μm (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P=.53). Conclusions The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE. Clinical Relevance: These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of

  16. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration

    PubMed Central

    Zhang, J; Bai, Y; Huang, L; Qi, Y; Zhang, Q; Li, S; Wu, Y; Li, X

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial (RPE) cells is a crucial causative factor responsible for the onset and progression of AMD. A2E, a major component of toxic lipofuscin implicated in AMD, is deposited in RPE cells with age. However, the mechanism whereby A2E may contribute to the pathogenesis of AMD remains unclear. We demonstrated that A2E was a danger signal of RPE cells, which induced autophagy and decreased cell viability in a concentration- and time-dependent manner. Within 15 min after the treatment of RPE with 25 μM A2E, the induction of autophagosome was detected by transmission electron microscopy. After continuous incubating RPE cells with A2E, intense punctate staining of LC3 and increased expression of LC3-II and Beclin-1 were identified. Meanwhile, the levels of intercellular adhesion molecule (ICAM), interleukin (IL)1β, IL2, IL-6, IL-8, IL-17A, IL-22, macrophage cationic peptide (MCP)-1, stromal cell-derived factor (SDF)-1, and vascular endothelial growth factor A (VEGFA) were elevated. The autophagic inhibitor 3-methyladenine (3-MA) and activator rapamycin were also used to verify the effect of autophagy on RPE cells against A2E. Our results revealed that 3-MA decreased the autophagosomes and LC3 puncta induced by A2E, increased inflammation-associated protein expression including ICAM, IL1β, IL2, IL-6, IL-8, IL-17A, IL-22, and SDF-1, and upregulated VEGFA expression. Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. The enhancement of autophagy has a protective role in RPE cells against the adverse effects of A2E by reducing the

  17. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration.

    PubMed

    Zhang, J; Bai, Y; Huang, L; Qi, Y; Zhang, Q; Li, S; Wu, Y; Li, X

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial (RPE) cells is a crucial causative factor responsible for the onset and progression of AMD. A2E, a major component of toxic lipofuscin implicated in AMD, is deposited in RPE cells with age. However, the mechanism whereby A2E may contribute to the pathogenesis of AMD remains unclear. We demonstrated that A2E was a danger signal of RPE cells, which induced autophagy and decreased cell viability in a concentration- and time-dependent manner. Within 15 min after the treatment of RPE with 25 μM A2E, the induction of autophagosome was detected by transmission electron microscopy. After continuous incubating RPE cells with A2E, intense punctate staining of LC3 and increased expression of LC3-II and Beclin-1 were identified. Meanwhile, the levels of intercellular adhesion molecule (ICAM), interleukin (IL)1β, IL2, IL-6, IL-8, IL-17A, IL-22, macrophage cationic peptide (MCP)-1, stromal cell-derived factor (SDF)-1, and vascular endothelial growth factor A (VEGFA) were elevated. The autophagic inhibitor 3-methyladenine (3-MA) and activator rapamycin were also used to verify the effect of autophagy on RPE cells against A2E. Our results revealed that 3-MA decreased the autophagosomes and LC3 puncta induced by A2E, increased inflammation-associated protein expression including ICAM, IL1β, IL2, IL-6, IL-8, IL-17A, IL-22, and SDF-1, and upregulated VEGFA expression. Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. The enhancement of autophagy has a protective role in RPE cells against the adverse effects of A2E by reducing the

  18. A novel fluorescence-based assay for measuring A2E removal from human retinal pigment epithelial cells to screen for age-related macular degeneration inhibitors.

    PubMed

    Jin, Hong Lan; Lee, Sung-Chan; Kwon, Yong Sam; Choung, Se-Young; Jeong, Kwang Won

    2016-01-01

    Age-related macular degeneration (AMD) is a common retinal disease that leads to irreversible central vision loss in the elderly population. Recent studies have identified many factors related to the development of dry AMD, such as aging, cigarette smoking, genetic predispositions, and oxidative stress, eventually inducing the accumulation of lipofuscin, which is one of the most critical risk factors. One of the major lipofuscins in retinal pigment epithelial (RPE) cells is N-retinylidene-N-retinylethanolamine (also known as A2E), a pyridinium bis-retinoid. Currently there is a lack of effective therapy to prevent or restore vision loss caused by dry AMD. Recent studies have shown that 430 nm blue light induces the oxidation of A2E and the activation of caspase-3 to subsequently cause the death of RPE cells, suggesting that removal of A2E from retinal pigment cells might be critical for preventing AMD. Here, we developed a fluorescence-labeled A2E analog (A2E-BDP) that functions similar to A2E in RPE cells, but is more sensitive to detection than A2E. A2E-BDP-based tracing of intracellular A2E will be helpful, not only for studying the accumulation and removal of A2E in human RPE cells but also for identifying possible inhibitors of AMD. PMID:26604166

  19. Genetics Home Reference: vitelliform macular dystrophy

    MedlinePlus

    ... faces. Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the ... structures in these cells that contain light-sensing pigments. It is unclear why PRPH2 mutations affect only ...

  20. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    PubMed Central

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  1. Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration.

    PubMed

    Szatmári-Tóth, M; Kristóf, E; Veréb, Z; Akhtar, S; Facskó, A; Fésüs, L; Kauppinen, A; Kaarniranta, K; Petrovski, G

    2016-01-01

    Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis. PMID:27607582

  2. Change of retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in exudative age-related macular degeneration

    PubMed Central

    Kim, Moosang; Kim, Eung Suk; Seo, Kyung Hoon; Yu, Seung-Young; Kwak, Hyung-Woo

    2016-01-01

    Purpose: The study aimed to investigate the quantitative changes of retinal pigment epithelial (RPE) atrophy during a 24-month follow-up period of anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (AMD). Materials and Methods: This is a retrospective study. Sixty-five eyes of 62 consecutive patients with naïve exudative AMD who had received treatment with anti-VEGF therapy and followed for more 24 months were enrolled. All patients received three initial monthly injections of anti-VEGF (ranibizumab or bevacizumab), followed by pro re nata or treat-and-extend protocol. Color fundus image, optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was performed to investigate the predictive factors found during univariate analysis to identify an association with increased RPE atrophic areas. Results: The mean number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 ± 1.298 mm2 at baseline and enlarged to 2.394 ± 1.940 mm2 after 24 months, which differed significantly (P = 0.001). Multiple regression analysis revealed that larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments were associated with increased RPE atrophic areas. Conclusions: RPE atrophy progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated with an increased risk of progression of RPE atrophy the following treatment. These findings may be useful to clinicians using intravitreal anti-VEGF for the treatment of exudative AMD, both for selecting an appropriate treatment plan and for predicting the progression of RPE atrophy. PMID:27488150

  3. Association between Blood Lead Levels and Age-Related Macular Degeneration

    PubMed Central

    Hwang, Ho Sik; Lee, Seung Bum; Jee, Donghyun

    2015-01-01

    Purpose To investigate the association between blood lead levels and prevalence of age-related macular degeneration (AMD). Methods A nationwide population-based cross-sectional study included 4,933 subjects aged over 40 years who participated in the 2008–2012 Korean National Health and Nutrition Examination Survey, and for whom fundus photographs were available. All participants underwent a standardized interview, evaluation of blood lead concentration, and a comprehensive ophthalmic examination. Digital fundus photographs (45°) were taken of both eyes under physiological mydriasis. All fundus photographs were graded using an international classification and grading system. Results Mean blood lead levels were 3.15 μg/dL in men and 2.27 μg/dL in women (P < 0.001). After adjusting for potential confounders including age, gender, smoking status, total cholesterol levels, triglyceride levels, heart problems and strokes, the adjusted odds ratio (OR) in women for any AMD was 1.86 (95% Confidence Interval [CI], 1.03–3.36) and for early AMD was 1.92 (95% CI, 1.06–3.48), for those in the highest quintile of lead level compared with the lowest quintile. In men, however, blood lead level was not significantly associated with AMD. Conclusions Blood lead levels were higher in men, but were only associated with AMD in women. Increased levels of blood lead may be involved in the pathogenesis of AMD development in women. PMID:26252225

  4. Allicin attenuates H₂O₂-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species.

    PubMed

    Tu, Gerile; Zhang, Yu-Feng; Wei, Wei; Li, Langen; Zhang, Yanmei; Yang, Jia; Xing, Yiqiao

    2016-03-01

    Retinal pigmented epithelial cell (RPE) oxidative stress is known to have a vital role in the etiology of age‑related macular degeneration (AMD). The present study aimed to investigate whether allicin, a natural product with antioxidant activity, was able to protect RPEs (ARPE‑19) from hydrogen peroxide (H2O2)‑induced damage, and to determine the underlying mechanisms. The 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyl tetrazolium bromide assay was used to determine cellular viability, and reactive oxygen species (ROS) were detected using a ROS Assay kit. The results demonstrated that allicin was able to protect ARPE‑19 cells from H2O2‑induced damage in a dose‑dependent manner. In addition, allicin attenuated oxidative stress by reducing the levels of intracellular ROS and malondialdehyde (MDA), and enhancing the glutathione/glutathione disulfide (GSSG) ratio. With regards to the underlying mechanism, allicin was able to markedly modulate the expression levels of ROS‑associated enzymes, including superoxide dismutase, NADPH oxidase 4 and NAD(P)H dehydrogenase quinone 1, and elevate the activity of nuclear factor erythroid 2‑related factor 2 in the H2O2‑stimulated ARPE‑19 cells. These results suggested that allicin may exert protective effects against H2O2‑induced cytotoxicity in RPEs via ROS regulation. PMID:26781848

  5. Macular changes resulting from papilloedema.

    PubMed

    Morris, A T; Sanders, M D

    1980-03-01

    Six cases are presented with macular changes in association with papilloedema; 4 suffered permanent visual loss. The present paper emphasises this previously infrequent finding and discusses the haemodynamic and mechanical factors responsible. The macular changes consisted of haemorrhages situated in front, within, or behind the retina, and occasionally the results of neovascular membrane formation produced secondary visual loss. Changes in the pigment epithelium were seen in 3 cases associated with choroidal folds. Macular stars rarely produce visual loss. Recognition of these changes is important in the assessment of the visual loss in papilloedema. PMID:7387954

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

    PubMed

    Anezaki, Katsunori; Nakano, Takeshi

    2014-01-01

    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

  7. Serum levels of lipid metabolites in age-related macular degeneration.

    PubMed

    Orban, Tivadar; Johnson, William M; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J; Palczewski, Krzysztof

    2015-11-01

    Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala(69)→Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD. PMID:26187344

  8. Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

    PubMed Central

    Örnek, Nurgül; Örnek, Kemal; Aydin, Süleyman; Yilmaz, Musa; Ölmez, Yaşar

    2016-01-01

    AIM To investigate the serum levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and adropin in age-related macular degeneration (AMD) patients. METHODS Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group. Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups. RESULTS AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness (P =0.01, 0.047, 0.025 and <0.001, respectively). Serum VEGFR-2 level revealed a significant decrease in AMD patients compared to controls (26.48±6.44 vs 30.42±7.92 ng/mL, P<0.001). There was an insignificant increase in serum adropin level in AMD patients (6.17±3.19 vs 5.79±2.71 ng/mL, P=0.4). Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness (r=-0.226, P=0.025) and a significant positive correlation with subfoveal choroidal thickness (r=0.2, P=0.048). CONCLUSION The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD. PMID:27162728

  9. Prospective Study of Plasma Homocysteine Level and Risk of Age-related Macular Degeneration in Women

    PubMed Central

    Christen, William G.; Cook, Nancy R.; Ridker, Paul M.; Buring, Julie E.

    2014-01-01

    Purpose Prospective data to examine the association of homocysteine and age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. Methods We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results During an average of 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually-significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.95–1.63; p for trend, 0.07) and visually-significant AMD (HR, 1.41; 95% CI, 0.92–2.17; p for trend, 0.052) in age- and treatment-adjusted analyses. Conclusions These prospective data from a large cohort of apparently-healthy women do not support a strong role for homocysteine in AMD occurrence. PMID:25777307

  10. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  11. Increased Macular Pigment Optical Density and Visual Acuity following Consumption of a Buttermilk Drink Containing Lutein-Enriched Egg Yolks: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    van der Made, Sanne M.; Kelly, Elton R.; Kijlstra, Aize; Plat, Jogchum

    2016-01-01

    Purpose. To study the effect of 1-year daily consumption of a dairy drink containing lutein-enriched egg yolks on macular pigment optical density (MPOD) and visual function parameters in elderly subjects with ocular drusen and/or retinal pigment abnormalities. Methods. One hundred and one subjects were recruited to participate in this randomized, double-blind, placebo-controlled parallel intervention trial. Statistical analyses were performed with 46 subjects in the lutein group and 43 in the control group. MPOD, best corrected visual acuity (BCVA, logMAR), and dark adaptation were measured at the start of the study, after 6 months and after 12 months. Plasma lutein and zeaxanthin concentrations were assessed at baseline and at the end of the study. Results. In the lutein group, plasma lutein concentrations increased significantly from 205 ng/mL at baseline to 399 ng/mL after twelve months of intervention. MPOD increased significantly from 0.45 to 0.52 and BCVA improved significantly from −0.04 to −0.09 LogMar. Differences in rod dark adaptation rate between both groups were not significant. Conclusion. Daily consumption of a dairy drink containing lutein-enriched egg yolks for one year improves visual acuity, MPOD, and plasma lutein concentration in elderly subjects with drusen and/or retinal pigment epithelial abnormalities. PMID:27064326

  12. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration

    PubMed Central

    Marazita, Mariela C.; Dugour, Andrea; Marquioni-Ramella, Melisa D.; Figueroa, Juan M.; Suburo, Angela M.

    2015-01-01

    Oxidative stress has a critical role in the pathogenesis of Age-related Macular Degeneration (AMD), a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. Stress-induced premature cellular senescence (SIPS) is postulated to contribute to this condition. In this study, we hypothesized that oxidative damage, promoted by endogenous or exogenous sources, could elicit a senescence response in RPE cells, which would in turn dysregulate the expression of major players in AMD pathogenic mechanisms. We showed that exposure of a human RPE cell line (ARPE-19) to a cigarette smoke concentrate (CSC), not only enhanced Reactive Oxygen Species (ROS) levels, but also induced 8-Hydroxydeoxyguanosine-immunoreactive (8-OHdG) DNA lesions and phosphorylated-Histone 2AX-immunoreactive (p-H2AX) nuclear foci. CSC-nuclear damage was followed by premature senescence as shown by positive senescence associated-β-galactosidase (SA-β-Gal) staining, and p16INK4a and p21Waf-Cip1 protein upregulation. N-acetylcysteine (NAC) treatment, a ROS scavenger, decreased senescence markers, thus supporting the role of oxidative damage in CSC-induced senescence activation. ARPE-19 senescent cultures were also established by exposure to hydrogen peroxide (H2O2), which is an endogenous stress source produced in the retina under photo-oxidation conditions. Senescent cells upregulated the proinflammatory cytokines IL-6 and IL-8, the main markers of the senescence-associated secretory phenotype (SASP). Most important, we show for the first time that senescent ARPE-19 cells upregulated vascular endothelial growth factor (VEGF) and simultaneously downregulated complement factor H (CFH) expression. Since both phenomena are involved in AMD pathogenesis, our results support the hypothesis that SIPS could be a principal player in the induction and progression of AMD. Moreover, they would also explain the striking association of this disease

  13. The relationship between the violet pigment PP-V production and intracellular ammonium level in Penicillium purpurogenum.

    PubMed

    Kojima, Ryo; Arai, Teppei; Matsufuji, Hiroshi; Kasumi, Takafumi; Watanabe, Taisuke; Ogihara, Jun

    2016-12-01

    Penicillium purpurogenum is the fungus that produces an azaphilone pigment. However, details about the pigment biosynthesis pathway are unknown. The violet pigment PP-V is the one of the main pigments biosynthesized by this fungus. This pigment contains an amino group in a pyran ring as its core structure. We focused on this pigment and examined the relationship between intracellular ammonium concentration and pigment production using glutamine as a nitrogen source. The intracellular ammonium level decreased about 1.5-fold in conditions favoring PP-V production. Moreover, P. purpurogenum was transferred to medium in which it commonly produces the related pigment PP-O after cultivating it in the presence or absence of glutamine to investigate whether this fungus biosynthesizes PP-V using surplus ammonium in cells. Only mycelia cultured in medium containing 10 mM glutamine produced the violet pigment, and simultaneously intracellular ammonium levels decreased under this condition. From comparisons of the amount of PP-V that was secreted with quantity of surplus intracellular ammonium, it is suggested that P. purpurogenum maintains ammonium homeostasis by excreting waste ammonium as PP-V. PMID:27368914

  14. The Effect of L-Carnitine Treatment on Levels of Malondialdehyde and Glutathione in Patients with Age Related Macular Degeneration

    PubMed Central

    Ates, Orhan; Alp, H. Hakan; Mumcu, Ugur; Azizi, Sedat; Cinici, Emine; Kiziltunc, Ahmet; Baykal, Orhan

    2008-01-01

    Objective: The aim of this study was to determine the antioxidant properties of the L-carnitine (LC) in the treatment of patients with age-related macular degeneration (AMD). Materials and Methods: This study involved 60 patients diagnosed with early AMD. The patients were divided into two groups. Group I was the study group that received LC supplementation for 3 months. Group II was the control group and did not consent to LC supplementation over the 3 months. At the end of the 3-month period, markers of lipid peroxidation, malondialdehyde (MDA) and reduced glutathione (GSH) were measured in the two groups. Results: In the study group, the MDA level was significantly reduced, while the GSH level was significantly increased at the end of the 3-month period (P<0.001). Conclusion: Our results suggest that LC may protect against oxidative damage by decreasing the MDA level, a marker of lipid peroxidation, and increasing GSH. PMID:25610013

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-11-01

    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

  17. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. PMID:26518628

  18. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

  19. Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years.

    PubMed

    Schwartz, Steven D; Tan, Gavin; Hosseini, Hamid; Nagiel, Aaron

    2016-04-01

    Advanced macular degeneration is an important cause of vision loss in the United States with over 2 million people affected by the disease. Despite substantial progress in the development of new therapies for wet AMD, the severe visual impairment associated with geographic atrophy in dry AMD or Stargardt disease remains untreatable. Recently, two phase I/II studies involving 18 patients with these diseases have demonstrated that it is possible to safely implant human embryonic stem cell-derived RPE (hESC-RPE) in an attempt to rescue photoreceptors and visual function. The anatomical and functional results are encouraging, with more than half of treated patients experiencing sustained improvements in visual acuity and demonstrating evidence of possible cellular engraftment. However, any conclusions remain tempered by the relatively short follow-up time, lack of a formal control group, poor initial visual acuity, and small number of patients. Aside from an instance of postoperative infectious endophthalmitis, no adverse events related to the cell therapy, such as hyperproliferation, tumorigenicity, or rejection-related inflammation were noted in this initial cohort of 18 patients. These first-in-human safety studies have opened the door to future studies enrolling patients with less advanced disease, treating other diseases that result in RPE loss, employing shorter immunosuppressive regimens, and using alternative strategies for RPE transplantation such as sheets of cells with or without scaffolding to mimic Bruch's membrane. The ultimate goal of these initial safety studies is to promote continued translation of complex biological therapies into meaningful treatment strategies that may address unmet medical needs. PMID:27116660

  20. Pigmented casts.

    PubMed

    Miteva, Mariya; Romanelli, Paolo; Tosti, Antonella

    2014-01-01

    Pigmented casts have been reported with variable frequency in scalp biopsies from alopecia areata, trichotillomania, chemotherapy-induced alopecia and postoperative (pressure induced) alopecia. Their presence and morphology in other scalp disorders has not been described. The authors assessed for the presence and morphology of pigmented casts in 308 transversely bisected scalp biopsies from nonscarring and scarring alopecia, referred to the Department of Dermatology, University of Miami within a year. The pigmented casts were present in 21 of 29 cases of alopecia areata (72%), 7 of 7 cases of trichotillomania (100%), 1 case of friction alopecia, 4 of 28 cases of central centrifugal cicatricial alopecia (14%), and 4 of 4 cases of dissecting cellulitis (100%). They did not show any distinguishing features except for the morphology in trichotillomania, which included twisted, linear (zip), and "button"-like pigment aggregation. The linear arrangement was found also in friction alopecia and dissecting cellulitis. Pigmented casts in the hair canals of miniaturized/vellus hairs was a clue to alopecia areata. Pigmented casts can be observed in biopsies of different hair disorders, but they are not specific for the diagnosis. Horizontal sections allow to better assess their morphology and the follicular level of presence of pigmented casts, which in the context of the other follicular findings may be a clue to the diagnosis. PMID:23823025

  1. A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo

    PubMed Central

    Paun, Constantin C.; Lechanteur, Yara T. E.; Groenewoud, Joannes M. M.; Altay, Lebriz; Schick, Tina; Daha, Mohamed R.; Fauser, Sascha; Hoyng, Carel B.; den Hollander, Anneke I.; de Jong, Eiko K.

    2016-01-01

    The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation in vitro. Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10−13) and complement activation levels in vivo (p = 8.31*10−9). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments. PMID:27241480

  2. A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo.

    PubMed

    Paun, Constantin C; Lechanteur, Yara T E; Groenewoud, Joannes M M; Altay, Lebriz; Schick, Tina; Daha, Mohamed R; Fauser, Sascha; Hoyng, Carel B; den Hollander, Anneke I; de Jong, Eiko K

    2016-01-01

    The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation in vitro. Here we describe a novel complotype composed of CFB (rs4151667)-CFB (rs641153)-CFH (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10(-13)) and complement activation levels in vivo (p = 8.31*10(-9)). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments. PMID:27241480

  3. Macular Degeneration

    MedlinePlus

    ... common early symptom. Dry AMD happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease ...

  4. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

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

    PubMed Central

    Bhutto, Imran; Lutty, Gerard

    2012-01-01

    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

  6. Methods for analysis of photosynthetic pigments and steady-state levels of intermediates of tetrapyrrole biosynthesis.

    PubMed

    Czarnecki, Olaf; Peter, Enrico; Grimm, Bernhard

    2011-01-01

    Tetrapyrroles and carotenoids are required for many indispensable functions in photosynthesis. Tetrapyrroles are essential metabolites for photosynthesis, redox reaction, and detoxification of reactive oxygen species and xenobiotics, while carotenoids function as accessory pigments, in photoprotection and in attraction to animals. Their branched metabolic pathways of synthesis and degradation are tightly controlled to provide adequate amounts of each metabolite (carotenoids/tetrapyrroles) and to prevent accumulation of photoreactive intermediates (tetrapyrroles). Many Arabidopsis mutants and transgenic plants have been reported to show variations in steady-state levels of tetrapyrrole intermediates and contents of different carotenoid species. It is a challenging task to determine the minute amounts of these metabolites to assess the metabolic flow and the activities of both pigment-synthesising and degrading pathways, to unravel limiting enzymatic steps of these biosynthetic pathways, and to characterise mutants with accumulating intermediates. In this chapter, we present a series of methods to qualify and quantify anabolic and catabolic intermediates of Arabidopsis tetrapyrrole metabolism, and describe a common method for quantification of different plant carotenoid species. Additionally, we introduce two methods for quantification of non-covalently bound haem. The approach of analysing steady-state levels of tetrapyrrole intermediates in plants, when applied in combination with analyses of transcripts, proteins, and enzyme activities, enables the biochemical and genetic elucidation of the tetrapyrrole pathway in wild-type plants, varieties, and mutants. Steady-state levels of tetrapyrrole intermediates are only up to 1/1,000 of the amounts of the accumulating end-products, chlorophyll, and haem. Although present in very low amounts, the accumulation and availability of tetrapyrrole intermediates have major consequences on the physiology and activity of

  7. Loosely coupled level sets for retinal layers and drusen segmentation in subjects with dry age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Novosel, Jelena; Wang, Ziyuan; de Jong, Henk; Vermeer, Koenraad A.; van Vliet, Lucas J.

    2016-03-01

    Optical coherence tomography (OCT) is used to produce high-resolution three-dimensional images of the retina, which permit the investigation of retinal irregularities. In dry age-related macular degeneration (AMD), a chronic eye disease that causes central vision loss, disruptions such as drusen and changes in retinal layer thicknesses occur which could be used as biomarkers for disease monitoring and diagnosis. Due to the topology disrupting pathology, existing segmentation methods often fail. Here, we present a solution for the segmentation of retinal layers in dry AMD subjects by extending our previously presented loosely coupled level sets framework which operates on attenuation coefficients. In eyes affected by AMD, Bruch's membrane becomes visible only below the drusen and our segmentation framework is adapted to delineate such a partially discernible interface. Furthermore, the initialization stage, which tentatively segments five interfaces, is modified to accommodate the appearance of drusen. This stage is based on Dijkstra's algorithm and combines prior knowledge on the shape of the interface, gradient and attenuation coefficient in the newly proposed cost function. This prior knowledge is incorporated by varying the weights for horizontal, diagonal and vertical edges. Finally, quantitative evaluation of the accuracy shows a good agreement between manual and automated segmentation.

  8. Macular Diplopia.

    PubMed

    Shippman, Sara; Cohen, Kenneth R; Heiser, Larissa

    2015-01-01

    Maculopathies affect point-to-point foveal correspondence causing diplopia. The effect that the maculopathies have on the interaction of central sensory fusion and peripheral fusion are different than the usual understanding of treatment for diplopia. This paper reviews the pathophysiology of macular diplopia, describes the binocular pathology causing the diplopia, discusses the clinical evaluation, and reviews the present treatments including some newer treatment techniques. PMID:26564922

  9. Effects of low-level laser therapy, electroacupuncture, and radiofrequency on the pigmentation and skin tone of adult women.

    PubMed

    Kim, Hee-Kyoung; Min, Kyoung-Ok; Choi, Jung-Hyun; Kim, Soon-Hee

    2016-05-01

    [Purpose] In this study, the effects of low-level laser therapy (LLLT), electroacupuncture (EA), and radiofrequency (RF), which are used in physical therapy, on the pigmentation and skin tone of adult women's faces were investigated to provide basic data for skin interventions. [Subjects and Methods] Thirty adult females were assigned to either an LLLT group (n=10), an EA group (n=10), or an RF group (n=10). The intervention was performed in two 15-minute sessions per week for six weeks. Subjects' skin tone and pigmentation were observed before and after the intervention. [Results] The EA group showed significant reductions in pigmentation in the left and right eye rims, as well as in the left cheek. The RF group showed significant post-intervention reductions in pigmentation under the left eye, as well as in the left and right eye rims and the left cheek. The LLLT group showed significant increases in skin tone in the forehead and both eye rims. The RF group showed significant increases in skin tone under both eyes. [Conclusion] The application of LLLT, EA, and RF had positive effects on pigmentation and skin tone of adult women's faces. PMID:27313340

  10. Effects of low-level laser therapy, electroacupuncture, and radiofrequency on the pigmentation and skin tone of adult women

    PubMed Central

    Kim, Hee-Kyoung; Min, Kyoung-Ok; Choi, Jung-Hyun; Kim, Soon-Hee

    2016-01-01

    [Purpose] In this study, the effects of low-level laser therapy (LLLT), electroacupuncture (EA), and radiofrequency (RF), which are used in physical therapy, on the pigmentation and skin tone of adult women’s faces were investigated to provide basic data for skin interventions. [Subjects and Methods] Thirty adult females were assigned to either an LLLT group (n=10), an EA group (n=10), or an RF group (n=10). The intervention was performed in two 15-minute sessions per week for six weeks. Subjects’ skin tone and pigmentation were observed before and after the intervention. [Results] The EA group showed significant reductions in pigmentation in the left and right eye rims, as well as in the left cheek. The RF group showed significant post-intervention reductions in pigmentation under the left eye, as well as in the left and right eye rims and the left cheek. The LLLT group showed significant increases in skin tone in the forehead and both eye rims. The RF group showed significant increases in skin tone under both eyes. [Conclusion] The application of LLLT, EA, and RF had positive effects on pigmentation and skin tone of adult women’s faces. PMID:27313340

  11. Omega-3 Supplementation Combined With Anti–Vascular Endothelial Growth Factor Lowers Vitreal Levels of Vascular Endothelial Growth Factor in Wet Age-Related Macular Degeneration

    PubMed Central

    REZENDE, FLAVIO A.; LAPALME, ERIC; QIAN, CYNTHIA X.; SMITH, LOIS E.; SANGIOVANNI, JOHN PAUL; SAPIEHA, PRZEMYSLAW

    2015-01-01

    PURPOSE To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment. DESIGN Prospective, randomized, open-label, single-center, clinical trial, consecutive interventional case series. METHODS The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n = 10) or without omega-3 fatty acids (group 2, n = 10). They were compared with an anti-VEGF treatment-naïve wet AMD group (group 3, n = 10) and an epiretinal membrane or macular hole group (group 4, n = 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3 months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively. RESULTS Patients receiving omega-3s (group 1) had significantly lower levels of vitreal VEGF-A (141.11 ± 61.89 pg/mL) when compared with group 2 (626.09 ± 279.27 pg/mL; P = .036) and group 3 (735.48 ± 216.43 pg/mL; P = .013), but similar levels to group 4 (235.81 ± 33.99 pg/mL; P=.215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements. CONCLUSIONS This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients. PMID:25089351

  12. Ageing and degeneration in the macular region: a clinico-pathological study.

    PubMed Central

    Sarks, S H

    1976-01-01

    Clinical and pathological examination was performed on 378 eyes from 216 patients aged 43 to 97 years. This series represented eyes in which the fundi were normal or showed various manifestations of senile macular degeneration. The eyes were divided into six groups according to the histological appearance of a linear deposit at the base of the retinal pigment cells. Groups I and II were considered to represent normal ageing, Groups III and IV the progressive development of senile macular degeneration and Groups V and VI the end-results. Group I showed no basal linear deposit. Thickening and hyalinization of Bruch's membrane was noted as early as the fifth decade. Group II showed patchy development of the basal linear deposit in relation to thickened or basophilic segments of Bruch's membrane, or over intercapillary hyalinization extending to the level of the outer surface of the choriocapillaris. Almost all eyes in these two groups retained a normal fundus appearance but visual acuity declined with age even in the absence of other causes. In Group III the basal deposit formed a thin continuous layer associated with moderate degeneration of the retinal pigment epithelium. More than half the eyes had developed a clinical disturbance of pigmentation and in most vision was reduced. Group IV was characterized by thickening of the deposit and more pronounced disturbance of the pigment epithelium. Clinically most eyes showed coarse pigmentary changes and vision was in the order of 6/24. 14-3 per cent of eyes in this group showed early neovascularization from the choroid. In Group V the pigment epithelium disappeared to produce circumscribed areas of depigmentation. The basal linear deposit could be traced throughout the depigmented area in most eyes. Thin fibrovascular sheets were found beneath the pigment epithelium in 41-7 per cent of eyes. Group VI represented disciform degeneration. The basal linear deposit could often be demonstrated as a disrupted hyalinized layer

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

    PubMed Central

    2014-01-01

    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

  14. Analysis of Risk Alleles and Complement Activation Levels in Familial and Non-Familial Age-Related Macular Degeneration

    PubMed Central

    Saksens, Nicole T. M.; Lechanteur, Yara T. E.; Verbakel, Sanne K.; Groenewoud, Joannes M. M.; Daha, Mohamed R.; Schick, Tina; Fauser, Sascha; Boon, Camiel J. F.; Hoyng, Carel B.; den Hollander, Anneke I.

    2016-01-01

    Aims Age-related macular degeneration (AMD) is a multifactorial disease, in which complement-mediated inflammation plays a pivotal role. A positive family history is an important risk factor for developing AMD. Certain lifestyle factors are shown to be significantly associated with AMD in non-familial cases, but not in familial cases. This study aimed to investigate whether the contribution of common genetic variants and complement activation levels differs between familial and sporadic cases with AMD. Methods and Results 1216 AMD patients (281 familial and 935 sporadic) and 1043 controls (143 unaffected members with a family history of AMD and 900 unrelated controls without a family history of AMD) were included in this study. Ophthalmic examinations were performed, and lifestyle and family history were documented with a questionnaire. Nine single nucleotide polymorphisms (SNPs) known to be associated with AMD were genotyped, and serum concentrations of complement components C3 and C3d were measured. Associations were assessed in familial and sporadic individuals. The association with risk alleles of the age-related maculopathy susceptibility 2 (ARMS2) gene was significantly stronger in sporadic AMD patients compared to familial cases (p = 0.017 for all AMD stages and p = 0.003 for advanced AMD, respectively). ARMS2 risk alleles had the largest effect in sporadic cases but were not significantly associated with AMD in densely affected families. The C3d/C3 ratio was a significant risk factor for AMD in sporadic cases and may also be associated with familial cases. In patients with a densely affected family this effect was particularly strong with ORs of 5.37 and 4.99 for all AMD and advanced AMD respectively. Conclusion This study suggests that in familial AMD patients, the common genetic risk variant in ARMS2 is less important compared to sporadic AMD. In contrast, factors leading to increased complement activation appear to play a larger role in patients with a

  15. Skin pigmentation evaluation in broilers fed natural and synthetic pigments.

    PubMed

    Castañeda, M P; Hirschler, E M; Sams, A R

    2005-01-01

    Broiler carcass skin color is important in the United States and Mexico. This study evaluated the use of natural and synthetic pigments in broiler diets at commercial levels. Birds were fed natural or synthetic pigments at low or high levels, simulating US and Mexican commercial practices. Skin color was measured during live production (3 to 7 wk of age) and after slaughter and chilling. The natural pigments had consistently greater skin b* values (yellowness) than the synthetic pigments. The high levels produced greater skin b* values than the low levels, regardless of source. The synthetic pigments had a slower increase in skin b* but reached the same level as the natural low by 7 wk. There was no difference in skin a* values (redness) due to pigment source or level or the age of the bird. By 7 wk, all pigment sources approached plateau levels in the blood, but the synthetic pigment diet produced higher blood levels of yellow and red pigments than the natural pigment diets. Processing intensified skin yellowness and reduced skin redness. These data suggest that although synthetic pigments might have been absorbed better than natural ones, natural pigments were more efficient at increasing skin yellowness and there were only small differences between high and low levels for each pigment source. This finding may allow reduction in pigment use and feed cost to achieve the same skin acceptance by the consumer. PMID:15685954

  16. Skin Pigment

    MedlinePlus

    ... Professional Version Pigment Disorders Overview of Skin Pigment Albinism Vitiligo Hyperpigmentation Melasma Melanin is the brown pigment ... dark-skinned people produce the most. People with albinism have little or no melanin and thus their ...

  17. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  18. Dietary carotenoid pigment supplementation influences hepatic lipid and mucopolysaccharide levels in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Page, G I; Russell, P M; Davies, S J

    2005-12-01

    We assessed the effects of dietary carotenoid pigment supplementation on liver histochemistry in the rainbow trout. One hundred and eight rainbow trout (mean mass 266+/-10 g) were assigned to each of three replicate tanks for each of three dietary treatments; astaxanthin, canthaxanthin, or control at a target dietary inclusion of 100 mg/kg, by top-coating a pigment-free commercially extruded basal diet (Trouw Aquaculture, U.K.). Fish were fed for 3 weeks at a ration of 1.2% body mass/day, in a recirculating freshwater system maintained at 16 degrees C. Frozen liver sections were stained for total lipids, unsaturated lipids, glycogen, mucopolysaccharides, glycogen phosphorylase and aspartate aminotransferase. Relative amounts were measured quantitatively by image analysis. Carotenoid treatment significantly (P<0.05) altered the total lipid profile and hepatic mucopolysaccharide contents of livers of rainbow trout. Results are discussed in relation to the catabolic potential of the liver in carotenoid pigment metabolism. PMID:16209931

  19. Iron deficiency anemia presenting with macular star.

    PubMed

    Trivedi, Bhakti P; Ravindran, Meenakshi; Pawar, Neelam; Ramakrishnan, Rengappa; Shelke, Vijaysai

    2015-10-01

    We report the case of 16-year-old girl who presented with sudden painless decreased vision in her right eye of 5 days' duration. Anterior segment examination in both eyes showed conjunctival pallor. Results of ophthalmoscopic examination and optical coherence tomography were consistent with macular preretinal hemorrhage in both eyes with macular star in the left eye. Hematologic investigation disclosed severe iron deficiency anaemia. After 2 months, with oral substitution therapy with ferrous ascorbate and improved iron levels, the patient's visual acuity improved and macular preretinal hemorrhage resolved in both eyes. PMID:26486041

  20. Reduction of Endogenous Angiogenesis Inhibitors in Bruch’s Membrane of the Submacular Region in Eyes With Age-Related Macular Degeneration

    PubMed Central

    Bhutto, Imran A.; Uno, Koichi; Merges, Carol; Zhang, Lei; McLeod, D. Scott; Lutty, Gerard A.

    2016-01-01

    Objectives To determine the relative levels of 3 potent inhibitors of angiogenesis (endostatin, pigment epithelium–derived factor, and thrombospondin 1) in the retinal pigment epithelium–Bruch’s membrane–choriocapillaris complex in the submacular region in aged control eyes and eyes with age-related macular degeneration (AMD). Methods Immunohistochemical analysis with antibodies against endostatin, pigment epithelium–derived factor, and thrombospondin 1 was performed on the macular region of aged control donor eyes (n=8; mean age, 79.8 years) and eyes with AMD (n=12; mean age, 83.9 years). Three independent masked observers scored the reaction product (scored from 0–7). Mean scores from the control eyes and the eyes with AMD were analyzed using 1-way analysis of variance and unpaired t test. Results In control eyes, strong immunoreactivity of all 3 inhibitors was observed in the retinal pigment epithelium–Bruch’s membrane–choriocapillaris complex. Immunoreactivity for endostatin, pigment epithelium–derived factor, and thrombospondin 1 in Bruch’s membrane was significantly lower in eyes with AMD compared with aged control eyes (analysis of variance, P=.003, P = .009, and P< .001, respectively). In the choriocapillaris, a significant reduction was observed in endostatin (analysis of variance, P=.02) and thrombospondin 1 (analysis of variance, P=.005) in eyes with AMD. Conclusions These findings suggest that endogenous angiogenesis inhibitors in the retinal pigment epithelium–Bruch’s membrane–choriocapillaris complex may provide a biochemical barrier for choroidal neovascular invasion. Clinical Relevance Decreased levels of angiogenic inhibitors at the retinal pigment epithelium–Bruch’s membrane–choriocapillaris complex in eyes with AMD make Bruch’s membrane vulnerable to choroidal neovascularization. PMID:18474778

  1. Complications of Macular Peeling

    PubMed Central

    Asencio-Duran, Mónica; Manzano-Muñoz, Beatriz; Vallejo-García, José Luis; García-Martínez, Jesús

    2015-01-01

    Macular peeling refers to the surgical technique for the removal of preretinal tissue or the internal limiting membrane (ILM) in the macula for several retinal disorders, ranging from epiretinal membranes (primary or secondary to diabetic retinopathy, retinal detachment…) to full-thickness macular holes, macular edema, foveal retinoschisis, and others. The technique has evolved in the last two decades, and the different instrumentations and adjuncts have progressively advanced turning into a safer, easier, and more useful tool for the vitreoretinal surgeon. Here, we describe the main milestones of macular peeling, drawing attention to its associated complications. PMID:26425351

  2. Complications of Macular Peeling.

    PubMed

    Asencio-Duran, Mónica; Manzano-Muñoz, Beatriz; Vallejo-García, José Luis; García-Martínez, Jesús

    2015-01-01

    Macular peeling refers to the surgical technique for the removal of preretinal tissue or the internal limiting membrane (ILM) in the macula for several retinal disorders, ranging from epiretinal membranes (primary or secondary to diabetic retinopathy, retinal detachment…) to full-thickness macular holes, macular edema, foveal retinoschisis, and others. The technique has evolved in the last two decades, and the different instrumentations and adjuncts have progressively advanced turning into a safer, easier, and more useful tool for the vitreoretinal surgeon. Here, we describe the main milestones of macular peeling, drawing attention to its associated complications. PMID:26425351

  3. Carotenoid accumulation in orange-pigmented Capsicum annuum fruit, regulated at multiple levels

    PubMed Central

    Rodriguez-Uribe, Laura; Guzman, Ivette; Rajapakse, Wathsala; Richins, Richard D.; O’Connell, Mary A.

    2012-01-01

    The pericarp of Capsicum fruit is a rich dietary source of carotenoids. Accumulation of these compounds may be controlled, in part, by gene transcription of biosynthetic enzymes. The carotenoid composition in a number of orange-coloured C. annuum cultivars was determined using HPLC and compared with transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs determined by qRT-PCR. There were unique carotenoid profiles as well as distinct patterns of transcription of carotenogenic enzymes within the seven orange-coloured cultivars. In one cultivar, ‘Fogo’, carrying the mutant ccs-3 allele, transcripts were detected for this gene, but no CCS protein accumulated. The premature stop termination in ccs-3 prevented expression of the biosynthetic activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two other orange-coloured cultivars, ‘Orange Grande’ and ‘Oriole’, both with wild-type versions of all four carotenogenic enzymes, no transcripts for Ccs were detected and no red pigments accumulated. Finally, in a third case, the orange-coloured cultivar, Canary, transcripts for all four of the wild-type carotenogenic enzymes were readily detected yet no CCS protein appeared to accumulate and no red carotenoids were synthesized. In the past, mutations in Psy and Ccs have been identified as the loci controlling colour in the fruit. Now there is evidence that a non-structural gene may control colour development in Capsicum. PMID:21948863

  4. Dependence of Photosynthetic Capacity, Photosynthetic Pigment Allocation, and Carbon Storage on Nitrogen Levels in Foliage of Aspen Stands

    NASA Technical Reports Server (NTRS)

    Middleton, Elizabeth M.; Sullivan, Joseph H.; Papagno, Andrea J.

    2000-01-01

    complexes and enzymes. In mature leaves, differences in pigment content vs. N among canopy strata were accentuated when N was expressed per unit leaf area (Mg cm (exp -2)) . However, the simplest log-linear relationship between a pigment variable and N was obtained for a ratio describing the relative allocation of photosynthetic pigment to Chl a (Chl a/[Chl b + carotenoids], microgram cm (exp -2)/ microgram cm-2) vs. %N (r (exp 2) = 0.90, n=343, P less than 0.001). Attainment of comparable A (sub max) Chl a content and relative Chl a allocation per unit N (mg cm (exp -2)) was achieved at different foliar N levels per canopy group: the lowest N requirement was for hazelnut leaves in the lowest, shaded stratum at the older, closed canopy site; the highest N requirement was in aspen leaves of the upper-most stratum at the younger, more open canopy site. These results highlight the differences in physiological responses between young and fully expanded leaves and show that sustaining those foliar constituents and processes important to C balance may require higher foliar N levels in leaves of establishing vs. mature aspen stands. There may be implications for remote-sensing assessments made for carbon balance in springtime, or over a landscape mosaic comprised of different aged stands.

  5. Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case-Control Study

    PubMed Central

    Osthoff, Michael; Dean, Melinda M.; Baird, Paul N.; Richardson, Andrea J.; Daniell, Mark; Guymer, Robyn H.; Eisen, Damon P.

    2015-01-01

    Background In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD. Methods MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls. Results MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (<0.5 μg/ml) was encountered less frequently in the late AMD group (35% vs 56%, p = 0.03). FCN2 and MBL2 allele frequencies were similarly distributed in early and late AMD cases compared with controls (p>0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD. Conclusions SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity. PMID:26207622

  6. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    PubMed Central

    Fronk, Aaron H; Vargis, Elizabeth

    2016-01-01

    The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included. PMID:27493715

  7. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations.

    PubMed

    Fronk, Aaron H; Vargis, Elizabeth

    2016-01-01

    The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included. PMID:27493715

  8. Association of gene polymorphism with serum levels of inflammatory and angiogenic factors in Pakistani patients with age-related macular degeneration

    PubMed Central

    Ambreen, Fareeha; Ismail, Muhammad

    2015-01-01

    Purpose To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients. Methods This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy age-matched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box–Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ2 tests applying Hardy–Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05. Results Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant

  9. Identification of the gene responsible for Best macular dystrophy.

    PubMed

    Petrukhin, K; Koisti, M J; Bakall, B; Li, W; Xie, G; Marknell, T; Sandgren, O; Forsman, K; Holmgren, G; Andreasson, S; Vujic, M; Bergen, A A; McGarty-Dugan, V; Figueroa, D; Austin, C P; Metzker, M L; Caskey, C T; Wadelius, C

    1998-07-01

    Best macular dystrophy (BMD), also known as vitelliform macular dystrophy (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration characterized by an abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. In pursuit of the disease gene, we limited the minimum genetic region by recombination breakpoint analysis and mapped to this region a novel retina-specific gene (VMD2). Genetic mapping data, identification of five independent disease-specific mutations and expression studies provide evidence that mutations within the candidate gene are a cause of BMD. The 3' UTR of the candidate gene contains a region of antisense complementarity to the 3' UTR of the ferritin heavy-chain gene (FTH1), indicating the possibility of antisense interaction between VMD2 and FTH1 transcripts. PMID:9662395

  10. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  11. A level-set method for pathology segmentation in fluorescein angiograms and en face retinal images of patients with age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Mohammad, Fatimah; Ansari, Rashid; Shahidi, Mahnaz

    2013-03-01

    The visibility and continuity of the inner segment outer segment (ISOS) junction layer of the photoreceptors on spectral domain optical coherence tomography images is known to be related to visual acuity in patients with age-related macular degeneration (AMD). Automatic detection and segmentation of lesions and pathologies in retinal images is crucial for the screening, diagnosis, and follow-up of patients with retinal diseases. One of the challenges of using the classical level-set algorithms for segmentation involves the placement of the initial contour. Manually defining the contour or randomly placing it in the image may lead to segmentation of erroneous structures. It is important to be able to automatically define the contour by using information provided by image features. We explored a level-set method which is based on the classical Chan-Vese model and which utilizes image feature information for automatic contour placement for the segmentation of pathologies in fluorescein angiograms and en face retinal images of the ISOS layer. This was accomplished by exploiting a priori knowledge of the shape and intensity distribution allowing the use of projection profiles to detect the presence of pathologies that are characterized by intensity differences with surrounding areas in retinal images. We first tested our method by applying it to fluorescein angiograms. We then applied our method to en face retinal images of patients with AMD. The experimental results included demonstrate that the proposed method provided a quick and improved outcome as compared to the classical Chan-Vese method in which the initial contour is randomly placed, thus indicating the potential to provide a more accurate and detailed view of changes in pathologies due to disease progression and treatment.

  12. Mitochondrial DNA Variants Mediate Energy Production and Expression Levels for CFH, C3 and EFEMP1 Genes: Implications for Age-Related Macular Degeneration

    PubMed Central

    Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Pavlis, Janelle M.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Hsu, Tiffany; Woo, Grace; Soe, Kyaw; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin

    2013-01-01

    Background Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). Methodology/Principal Findings Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. Conclusion/Significance Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD. PMID:23365660

  13. Clinicopathologic findings in Best vitelliform macular dystrophy

    PubMed Central

    Zhang, Qing; Small, Kent W.

    2012-01-01

    Purpose To correlate the clinical and histopathologic features of Best vitelliform macular dystrophy (BVMD). Methods Two eyes were obtained postmortem from a patient with BVMD. The patient’s clinical information was reviewed. Series sections of the globes were performed and sequentially stained with hematoxylin-eosin, periodic acid-Schiff or Masson trichrome. A section of the left macula was submitted for electron microscopic processing. Histopathologic findings were reconstructed in a scaled two-dimensional map and compared with fundus photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) images. Results The macular lesion of the right eye was identified as a well-demarcated region with pigment, elevated submacular yellow material and subretinal fluid. This corresponded histopathologically to a well-circumscribed area of RPE hyperplasia, accumulation of lipofuscin in the RPE, deposition of granular material in the photoreceptors, macrophages and drusen. The left eye displayed a 1 disc diameter chorioretinal scar with surrounding shallow fluid and submacular pigment. This corresponded to RPE changes and a fibrocellular proliferation in the choriocapillaris. Conclusion Histopathologic mapping revealed retinal edema, RPE abnormalities, drusen and a chorioretinal scar in BVMD that correlated with the fundus, FFA, FAF and OCT findings. PMID:21136072

  14. Dark adaptation in patients with Best vitelliform macular dystrophy.

    PubMed Central

    Baca, W; Fishman, G A; Alexander, K R; Glenn, A M

    1994-01-01

    Psychophysical dark adaptation studies were performed in six patients with Best vitelliform macular dystrophy (BVMD) using a Goldmann-Weekers dark adaptometer. Prebleach thresholds were determined before obtaining a postbleach full recovery curve. Unlike patients with Stargardt macular dystrophy, all patients with BVMD showed a normal time to reach their baseline dark adapted thresholds after bleaching of their rod visual pigment when tested in clinically normal appearing retina. Although a lipofuscin material accumulates within retinal pigment epithelial cells in patients with either Best or Stargardt dystrophy, functional findings pertaining to recovery of rod dark adaptation thresholds as well as electro-oculogram light peak to dark trough ratios are different in these two disorders. PMID:8060924

  15. Dark adaptation in patients with Best vitelliform macular dystrophy.

    PubMed

    Baca, W; Fishman, G A; Alexander, K R; Glenn, A M

    1994-06-01

    Psychophysical dark adaptation studies were performed in six patients with Best vitelliform macular dystrophy (BVMD) using a Goldmann-Weekers dark adaptometer. Prebleach thresholds were determined before obtaining a postbleach full recovery curve. Unlike patients with Stargardt macular dystrophy, all patients with BVMD showed a normal time to reach their baseline dark adapted thresholds after bleaching of their rod visual pigment when tested in clinically normal appearing retina. Although a lipofuscin material accumulates within retinal pigment epithelial cells in patients with either Best or Stargardt dystrophy, functional findings pertaining to recovery of rod dark adaptation thresholds as well as electro-oculogram light peak to dark trough ratios are different in these two disorders. PMID:8060924

  16. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  17. Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

    PubMed Central

    Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

    2011-01-01

    Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

  18. Photosynthetic Pigments in Diatoms

    PubMed Central

    Kuczynska, Paulina; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

    2015-01-01

    Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries. PMID:26389924

  19. Photosynthetic Pigments in Diatoms.

    PubMed

    Kuczynska, Paulina; Jemiola-Rzeminska, Malgorzata; Strzalka, Kazimierz

    2015-09-01

    Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries. PMID:26389924

  20. Diabetic Macular Edema

    NASA Astrophysics Data System (ADS)

    Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

    The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

  1. Birthmarks - pigmented

    MedlinePlus

    ... its own appearance: Cafe-au-lait spots are light tan, the color of coffee with milk. Moles are small clusters of colored skin cells. Mongolian spots (also called Mongolian blue ... dark or light skin Growth of hair from pigmented skin Skin ...

  2. In vivo micropathology of Best macular dystrophy with optical coherence tomography.

    PubMed

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

    2003-02-01

    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 known VMD2 mutations, were included. OCT scans were recorded in the central retina and longitudinal reflectivity profiles were analysed. The central retina in BMD showed different OCT abnormalities at or near the level of the highly reflective deep retinal band termed the outer retina-choroid complex (ORCC). Two types of ORCC change were noted to occur either separately or together: (1) splitting with or without intervening hyporeflective areas; and (2) elevation. Longitudinal study of a BMD patient indicated that such abnormalities were dynamic and changed in type and degree with time. The pathogenetic sequence in BMD may begin with defective fluid transport across the RPE secondary to the channelopathy in the basolateral membrane. In the macula, this leads to an abnormal interface with adjacent structures at both apical and basal surfaces of the RPE. The disease process results in detachments of the neurosensory retina, such as in central serous chorioretinopathy, and sub-RPE pathology resembling some stages of age-related macular degeneration, with eventual loss of photoreceptors, inner retina and central vision. PMID:12565808

  3. Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration.

    PubMed

    Zeng, Shemin; Whitmore, S Scott; Sohn, Elliott H; Riker, Megan J; Wiley, Luke A; Scheetz, Todd E; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

    2016-02-01

    Age-related macular degeneration (AMD) is a common, blinding disease of the elderly in which macular photoreceptor cells, retinal pigment epithelium and choriocapillaris endothelial cells ultimately degenerate. Recent studies have found that degeneration of the choriocapillaris occurs early in this disease and that endothelial cell drop-out is concomitant with increased deposition of the complement membrane attack complex (MAC) at the choroidal endothelium. However, the impact of MAC injury to choroidal endothelial cells is poorly understood. To model this event in vitro, and to study the downstream consequences of MAC injury, endothelial cells were exposed to complement from human serum, compared to heat-inactivated serum, which lacks complement components. Cells exposed to complement components in human serum showed increased labelling with antibodies directed against the MAC, time- and dose-dependent cell death, as assessed by lactate dehydrogenase assay and increased permeability. RNA-Seq analysis following complement injury revealed increased expression of genes associated with angiogenesis including matrix metalloproteinase (MMP)-3 and -9, and VEGF-A. The MAC-induced increase in MMP9 RNA expression was validated using C5-depleted serum compared to C5-reconstituted serum. Increased levels of MMP9 were also established, using western blot and zymography. These data suggest that, in addition to cell lysis, complement attack on choroidal endothelial cells promotes an angiogenic phenotype in surviving cells. PMID:26564985

  4. Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

    PubMed Central

    Pinazo-Durán, Maria D.; Gómez-Ulla, Francisco; Arias, Luis; Araiz, Javier; Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; García-Medina, Jose J.; López-Gálvez, Maria Isabel; Manzanas, Lucía; Salas, Anna; Zapata, Miguel; Diaz-Llopis, Manuel; García-Layana, Alfredo

    2014-01-01

    Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids (ω-3) supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain). Results. High dietary intakes of ω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD. PMID:24672708

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

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    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

  6. VMD2 mutations in vitelliform macular dystrophy (Best disease) and other maculopathies.

    PubMed

    White, K; Marquardt, A; Weber, B H

    2000-01-01

    Mutations in the gene VMD2 are associated with autosomal dominant vitelliform macular dystrophy (Best disease). VMD2 is expressed in the retinal pigment epithelium and codes for a 585 amino acid putative transmembrane protein with undetermined functional properties. To date, 48 different mutations, predominantly missense, have been described in Best disease families. These mutations generally affect amino acids in the first 50% of the protein, and occur in four distinct clusters possibly representing regions of functional importance. VMD2 has also been investigated in other macular diseases. Mutations have been documented in a significant percentage of patients with adult vitelliform macular dystrophy (AVMD) and in a single case of "bull's-eye" maculopathy. Results of analysis in two large series of individuals with age-related macular degeneration (AMD) suggest that VMD2 does not play a major role in this prevalent disorder. PMID:10737974

  7. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Degeneration Diagnosis: How is AMD diagnosed? Macular Degeneration Treatment: How is AMD Treated? Macular ... macular degeneration (AMD) is a deterioration or breakdown of the eye's macula. The macula is a small area in the ...

  8. Melanization and phagocytosis: implications for age related macular degeneration.

    PubMed

    Sarangarajan, Rangaprasad; Apte, Shireesh P

    2005-01-01

    Signaling pathways that upregulate melanization in the retinal pigment epithelium (RPE) may also be implicated in the downregulation of rod outer segment (ROS) phagocytosis by the RPE. Melanization activating pathways may also modulate oxygen consumption by the photoreceptors, apolipoprotein E4 levels, and the rate of photoisomerization events such that the net effect may be a reduction in drusen and/or lipofuscin accumulation. An increase in melanin at the apical microvilli of the RPE may shield ROS from light thereby contributing in part to the decrease in the rate of ROS phagocytosis. This decrease in ROS phagocytosis by the RPE may serve to maintain a balance between ingestion and degradation/recycling thereby avoiding an increase to its already substantial metabolic load. Several experimental drugs for age related macular degeneration (ARMD) coincidentally are also capable of decreasing the rate of ROS phagocytosis. This review attempts to identify the signaling pathways that may link the upregulation of melanization to the downregulation of ROS phagocytosis. Phagocytic pathways that are modulated by melanization need to be studied in isolation to determine what role, if any, they possess in ameliorating the onset and progression of ARMD. Many more empirical studies are needed to unravel specific pathways and mechanisms that seem to link melanization with ARMD. PMID:16030499

  9. Proline levels, oxidative metabolism and photosynthetic pigments during in vitro growth and acclimatization of Pitcairnia encholirioides L.B. Sm. (Bromeliaceae).

    PubMed

    Resende, C F; Braga, V F; Pereira, P F; Silva, C J; Vale, V F; Bianchetti, R E; Forzza, R C; Ribeiro, C; Peixoto, P H P

    2016-02-01

    This study aimed to evaluate the variation in the levels of proline, oxidative metabolism and photosynthetic pigments in plants of Pitcairnia encholirioides grown in vitro under different conditions and after acclimatization. The analyses were performed after 150 days of in vitro cultivation in MS media supplemented with 10 µM GA3 or 0.2 µM NAA, sucrose at 15 or 30 g L-1, in test tubes which allowed gas exchange or in a hermetically sealed system, and 180 days after acclimatization. The in vitro maintenance in hermetically sealed flasks, with GA3 and 15 g L-1 sucrose had adverse metabolic effects, which was demonstrated by the lower proline and photosynthetic pigments accumulation and by the increase in antioxidant enzymes activities. After acclimatization, differences for proline and photosynthetic pigments were no longer found and the enzymatic activities ranged unevenly. The results suggest that the in vitro cultivation in media with 0.2 µM NAA and 30 g L-1 sucrose, in test tubes capped with closures which allowed gas exchange, is more suitable for micropropagation of P. encholirioides, providing a prolonged maintenance of in vitro cultures and plantlets with superior quality for ex vitro development. PMID:26909639

  10. INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA

    PubMed Central

    Bailey, Clare; Loewenstein, Anat; Massin, Pascale

    2015-01-01

    Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans. PMID:26352555

  11. Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study

    PubMed Central

    Dow, Coad Thomas; Harley, Calvin B

    2016-01-01

    Purpose Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. Method Thirty-eight (38) patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. Results The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). Conclusion The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. PMID:26869760

  12. Macular carotenoids and age-related maculopathy.

    PubMed

    O'Connell, Eamonn; Neelam, Kumari; Nolan, John; Au Eong, Kah-Guan; Beatty, Stephan

    2006-11-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary supplementation with these carotenoids might prevent, delay, or modify the course of ARM. This article discusses the scientific rationale supporting the hypothesis that L and Z are protective against ARM, and presents the recent evidence germane to this theory. PMID:17160199

  13. Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity.

    PubMed

    Saksens, Nicole T M; Krebs, Mark P; Schoenmaker-Koller, Frederieke E; Hicks, Wanda; Yu, Minzhong; Shi, Lanying; Rowe, Lucy; Collin, Gayle B; Charette, Jeremy R; Letteboer, Stef J; Neveling, Kornelia; van Moorsel, Tamara W; Abu-Ltaif, Sleiman; De Baere, Elfride; Walraedt, Sophie; Banfi, Sandro; Simonelli, Francesca; Cremers, Frans P M; Boon, Camiel J F; Roepman, Ronald; Leroy, Bart P; Peachey, Neal S; Hoyng, Carel B; Nishina, Patsy M; den Hollander, Anneke I

    2016-02-01

    Butterfly-shaped pigment dystrophy is an eye disease characterized by lesions in the macula that can resemble the wings of a butterfly. Here we report the identification of heterozygous missense mutations in the CTNNA1 gene (encoding α-catenin 1) in three families with butterfly-shaped pigment dystrophy. In addition, we identified a Ctnna1 missense mutation in a chemically induced mouse mutant, tvrm5. Parallel clinical phenotypes were observed in the retinal pigment epithelium (RPE) of individuals with butterfly-shaped pigment dystrophy and in tvrm5 mice, including pigmentary abnormalities, focal thickening and elevated lesions, and decreased light-activated responses. Morphological studies in tvrm5 mice demonstrated increased cell shedding and the presence of large multinucleated RPE cells, suggesting defects in intercellular adhesion and cytokinesis. This study identifies CTNNA1 gene variants as a cause of macular dystrophy, indicates that CTNNA1 is involved in maintaining RPE integrity and suggests that other components that participate in intercellular adhesion may be implicated in macular disease. PMID:26691986

  14. Mutations in CTNNA1 cause butterfly-shaped pigment dystrophy and perturbed retinal pigment epithelium integrity

    PubMed Central

    Saksens, Nicole T.M.; Krebs, Mark P.; Schoenmaker-Koller, Frederieke E.; Hicks, Wanda; Yu, Minzhong; Shi, Lanying; Rowe, Lucy; Collin, Gayle B.; Charette, Jeremy R.; Letteboer, Stef J.; Neveling, Kornelia; van Moorsel, Tamara W.; Abu-Ltaif, Sleiman; De Baere, Elfride; Walraedt, Sophie; Banfi, Sandro; Simonelli, Francesca; Cremers, Frans P.M.; Boon, Camiel J.F.; Roepman, Ronald; Leroy, Bart P.; Peachey, Neal S.; Hoyng, Carel B.; Nishina, Patsy M.; den Hollander, Anneke I.

    2015-01-01

    Butterfly-shaped pigment dystrophy is an eye disease characterized by lesions in the macula that can resemble the wings of a butterfly. Here, we report the identification of heterozygous missense mutations in the α-catenin 1 (CTNNA1) gene in three families with butterfly-shaped pigment dystrophy. In addition, we identified a Ctnna1 missense mutation in a chemically induced mouse mutant, tvrm5. Parallel clinical phenotypes were observed in the retinal pigment epithelium (RPE) of individuals with butterfly-shaped pigment dystrophy and in tvrm5 mice, including pigmentary abnormalities, focal thickening and elevated lesions, and decreased light-activated responses. Morphological studies in tvrm5 mice revealed increased cell shedding and large multinucleated RPE cells, suggesting defects in intercellular adhesion and cytokinesis. This study identifies CTNNA1 gene variants as a cause of macular dystrophy, suggests that CTNNA1 is involved in maintaining RPE integrity, and suggests that other components that participate in intercellular adhesion may be implicated in macular disease. PMID:26691986

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

    PubMed

    Butler, Michael W; McGraw, Kevin J

    2013-07-15

    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

  16. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

  17. Expression of Human Complement Factor H Prevents Age-Related Macular Degeneration–Like Retina Damage and Kidney Abnormalities in Aged Cfh Knockout Mice

    PubMed Central

    Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B.; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G.; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M.; Bowes Rickman, Catherine

    2016-01-01

    Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh−/−) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh−/− mice, and transgenics had a thicker outer nuclear layer and less sub–retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets. PMID:25447048

  18. Macular and serum carotenoid concentrations in patients with malabsorption syndromes.

    PubMed

    Ward, Matthew S; Zhao, Da You; Bernstein, Paul S

    2008-03-01

    The carotenoids lutein and zeaxanthin are believed to protect the human macula by absorbing blue light and quenching free radicals. Intestinal malabsorption syndromes such as celiac and Crohn's disease are known to cause deficiencies of lipid-soluble nutrients. We hypothesized that subjects with nutrient malabsorption syndromes will demonstrate lower carotenoid levels in the macula and blood, and that these lower levels may correlate with early-onset maculopathy. Resonance Raman spectrographic (RRS) measurements of macular carotenoid levels were collected from subjects with and without a history of malabsorption syndromes. Carotenoids were extracted from serum and analyzed by high performance liquid chromatography (HPLC). Subjects with malabsorption (n = 22) had 37% lower levels of macular carotenoids on average versus controls (n = 25, P < 0.001). Malabsorption was not associated with decreased serum carotenoid levels. Convincing signs of early maculopathy were not observed. We conclude that intestinal malabsorption results in lower macular carotenoid levels. PMID:19081745

  19. Skin Pigmentation Disorders

    MedlinePlus

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  20. The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway.

    PubMed

    Eidet, J R; Reppe, S; Pasovic, L; Olstad, O K; Lyberg, T; Khan, A Z; Fostad, I G; Chen, D F; Utheim, T P

    2016-01-01

    Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin's potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated. PMID:26940175

  1. The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway

    PubMed Central

    Eidet, J. R.; Reppe, S.; Pasovic, L.; Olstad, O. K.; Lyberg, T.; Khan, A. Z.; Fostad, I. G.; Chen, D. F.; Utheim, T. P.

    2016-01-01

    Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin’s potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated. PMID:26940175

  2. Achondroplasia and Macular Coloboma

    PubMed Central

    Ahoor, M. H.; Amizadeh, Y.; Sorkhabi, R.

    2015-01-01

    Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia. PMID:26692730

  3. Achondroplasia and Macular Coloboma.

    PubMed

    Ahoor, M H; Amizadeh, Y; Sorkhabi, R

    2015-01-01

    Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia. PMID:26692730

  4. Sunlight Exposure, Pigmentation, and Incident Age-Related Macular Degeneration

    PubMed Central

    Klein, Barbara E. K.; Howard, Kerri P.; Iyengar, Sudha K.; Sivakumaran, Theru A.; Meyers, Kristin J.; Cruickshanks, Karen J.; Klein, Ronald

    2014-01-01

    Purpose. Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD. Methods. Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color. Results. Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD. Conclusions. Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype. PMID:25125603

  5. Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is not Increased in Non-Lesion Areas of Retina.

    PubMed

    Sparrow, Janet R; Duncker, Tobias; Woods, Russell; Delori, François C

    2016-01-01

    Since the lipofuscin of retinal pigment epithelial (RPE) cells has been implicated in the pathogenesis of Best vitelliform macular dystrophy, we quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be within normal limits for age. By spectral domain optical coherence tomography (SD-OCT) vitelliform lesions presented as fluid-filled subretinal detachments containing reflective material. We discuss photoreceptor outer segment debris as the source of the intense fluorescence of these lesions and loss of anion channel functioning as an explanation for the bullous photoreceptor-RPE detachment. Unexplained is the propensity of the disease for central retina. PMID:26427423

  6. Age-Related Macular Degeneration: Advances in Management and Diagnosis.

    PubMed

    Yonekawa, Yoshihiro; Miller, Joan W; Kim, Ivana K

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  7. [Diagnostic Criteria for Atrophic Age-related Macular Degeneration].

    PubMed

    Takahashi, Kanji; Shiraga, Fumio; Ishida, Susumu; Kamei, Motohiro; Yanagi, Yasuo; Yoshimura, Nagahisa

    2015-10-01

    Diagnostic criteria for dry age-related macular degeneration is described. Criteria include visual acuity, fundscopic findings, diagnostic image findings, exclusion criteria and classification of severity grades. Essential findings to make diagnosis as "geographic atrophy" are, 1) at least 250 μm in diameter, 2) round/oval/cluster-like or geographic in shape, 3) sharp delineation, 4) hypopigmentation or depigmentation in retinal pigment epithelium, 5) choroidal vessels are more visible than in surrounding area. Severity grades were classified as mild, medium and severe by relation of geographic atrophy to the fovea and attendant findings. PMID:26571627

  8. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  9. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

    PubMed Central

    Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

    2014-01-01

    Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

  10. Macular morphology and response to ranibizumab treatment in patients with wet age-related macular degeneration

    PubMed Central

    Dervenis, Nikolaos; Younis, Saad

    2016-01-01

    Purpose The purpose of this study was to assess whether specific characteristics of spectral domain optical coherence tomography (SD-OCT) affect structural and functional outcomes and number of injections needed in ranibizumab (0.05 mL of 10 mg/mL Lucentis solution)-treated wet age-related macular degeneration (AMD) patients. Patients and methods This retrospective case series included 62 newly diagnosed wet AMD patients treated with three monthly intravitreal ranibizumab injections followed by monthly follow-up and pro re nata retreatment. The presence of dome-shaped pigment epithelial detachment (PED), disruption of the retinal pigment epithelium (RPE), and subretinal and intraretinal fluid was associated with changes in Early Treatment of Diabetic Retinopathy Study visual acuity, central macular thickness (CMT), and number of injections needed during the 6-month follow-up. Results The presence of PED was associated with lower values of CMT at presentation (399 μm [±132 μm] vs 310 μm [±51 μm], P=0.005). The presence of RPE disruption was associated with worse visual acuity in month 6 (0.36 [±0.22] vs 0.61 [0.45], P=0.027) and fewer injections (4.23 [±0.92] vs 3.55 [±0.60], P=0.007). The presence of intraretinal fluid at presentation was associated with worse visual acuity outcomes in month 4 (P=0.045) but not in month 6. Conclusion The dome-shaped PED was associated with lower CMT at presentation, but it did not affect response to treatment. RPE disruption was associated with worse functional outcomes with fewer injections. Intraretinal fluid at presentation may suggest delayed response to treatment. Individualized SD-OCT analysis could lead to individualized approach to wet AMD patients. SD-OCT can offer imaging biomarkers to assess the prognosis of anti-VEGF treatment in AMD patients. PMID:27366051

  11. Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

    PubMed Central

    Parmeggiani, Francesco; Sorrentino, Francesco S.; Romano, Mario R.; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Nadai, Katia; Bonomo Roversi, Elia; Franceschelli, Paola; Sebastiani, Adolfo

    2013-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch's membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease. PMID:24369445

  12. Ziv-aflibercept in macular disease

    PubMed Central

    Mansour, Ahmad M; Al-Ghadban, Sara I; Yunis, Muhammad H; El-Sabban, Marwan E

    2015-01-01

    Background/aims Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis. Methods Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA. Results There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab. Conclusions Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept. Trial registration number NCT02173873. PMID:25677668

  13. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. PMID:26292978

  14. Effect of Storage Temperature on Key Functions of Cultured Retinal Pigment Epithelial Cells

    PubMed Central

    Pasovic, Lara; Eidet, Jon Roger; Brusletto, Berit S.; Lyberg, Torstein; Utheim, Tor P.

    2015-01-01

    Purpose. Replacement of the diseased retinal pigment epithelium (RPE) with cells capable of performing the specialized functions of the RPE is the aim of cell replacement therapy for treatment of macular degenerative diseases. A storage method for RPE is likely to become a prerequisite for the establishment of such treatment. Herein, we analyze the effect of storage temperature on key functions of cultured RPE cells. Methods. Cultured ARPE-19 cells were stored in Minimum Essential Medium at 4°C, 16°C, and 37°C for seven days. Total RNA was isolated and the gene expression profile was determined using DNA microarrays. Comparison of the microarray expression values with qRT-PCR analysis of selected genes validated the results. Results. Expression levels of several key genes involved in phagocytosis, pigment synthesis, the visual cycle, adherens, and tight junctions, and glucose and ion transport were maintained close to control levels in cultures stored at 4°C and 16°C. Cultures stored at 37°C displayed regulational changes in a larger subset of genes related to phagocytosis, adherens, and tight junctions. Conclusion. RPE cultures stored at 4°C and 16°C for one week are capable of maintaining the expression levels of genes important for key RPE functions close to control levels. PMID:26448872

  15. Macular protection with IOLs

    NASA Astrophysics Data System (ADS)

    Soderberg, Per G.; Lofgren, Stefan; Ayala, Marcelo; Dong, Xiuqin; Kakar, Manoj; Mody, Vino; Meyer, Linda; Laurell, Carl-Gustaf

    2004-07-01

    The clinical outcome within one month after phacoemulsification cataract extraction with implantation of the blue-blocking SN60AT IOL was examined prospectively and compared to a retrospectively examined material of implantations of the equivalent SA30AL without blue-blocker. There was no difference in best corrected visual acuity gain between the two lenses. In addition, the subjective color perception was examined for with a questionnaire after the first implantation of blue-blocking IOL and after the second implantation of blue-blocking IOL. Only one patient noted a changed color perception. There are thus strong theoretical reasons to block blue light in IOLs and no short term clinical inconvenience. But, it remains to be proven in long term follow up studies that the blue-blocking IOL protects against macular degeneration.

  16. Diabetic Macular Edema

    PubMed Central

    Gundogan, Fatih C.; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

    2016-01-01

    Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. Sources of data selection: The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article. PMID:27182271

  17. Inflammation and its role in age-related macular degeneration.

    PubMed

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms. PMID:26852158

  18. Macular Degeneration - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Macular Degeneration URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Macular Degeneration - Multiple Languages To use the sharing features on ...

  19. Intrachoroidal Neovascularization in Transgenic Mice Overexpressing Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium

    PubMed Central

    Schwesinger, Catherine; Yee, Charles; Rohan, Richard M.; Joussen, Antonia M.; Fernandez, Antonio; Meyer, Tobias N.; Poulaki, Vassiliki; Ma, Joseph J. K.; Redmond, T. Michael; Liu, Suyan; Adamis, Anthony P.; D’Amato, Robert J.

    2001-01-01

    Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch’s membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE65 promoter) coupled to murine VEGF164 cDNA with a rabbit β-globin-3′ UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch’s membrane. These results support the hypothesis that additional insults to the integrity of Bruch’s membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth. PMID:11238064

  20. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration

    PubMed Central

    Ueda, Keiko; Zhao, Jin; Kim, Hye Jin; Sparrow, Janet R.

    2016-01-01

    Adducts of retinaldehyde (bisretinoids) form nonenzymatically in photoreceptor cells and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin; these fluorophores are implicated in the pathogenesis of inherited and age-related macular degeneration (AMD). Here we demonstrate that bisretinoid photodegradation is ongoing in the eye. High-performance liquid chromatography (HPLC) analysis of eyes of dark-reared and cyclic light-reared wild-type mice, together with comparisons of pigmented versus albino mice, revealed a relationship between intraocular light and reduced levels of the bisretinoids A2E and A2-glycero-phosphoethanolamine (A2-GPE). Analysis of the bisretinoids A2E, A2-GPE, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and all-trans-retinal dimer-phosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4−/− mice reared in cyclic light compared with darkness. In albino Abca4−/− mice receiving a diet supplemented with the antioxidant vitamin E, higher levels of RPE bisretinoid were evidenced by HPLC analysis and quantitation of fundus autofluorescence; this effect is consistent with photooxidative processes known to precede bisretinoid degradation. Amelioration of outer nuclear layer thinning indicated that vitamin E treatment protected photoreceptor cells. Conversely, in-cage exposure to short-wavelength light resulted in reduced fundus autofluorescence, decreased HPLC-quantified A2E, outer nuclear layer thinning, and increased methylglyoxal (MG)-adducted protein. MG was also released upon bisretinoid photodegradation in cells. We suggest that the lower levels of these diretinal adducts in cyclic light-reared and albino mice reflect photodegradative loss of bisretinoid. These mechanisms may underlie associations among AMD risk, oxidative mechanisms, and lifetime light exposure. PMID:27274068

  1. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration.

    PubMed

    Ueda, Keiko; Zhao, Jin; Kim, Hye Jin; Sparrow, Janet R

    2016-06-21

    Adducts of retinaldehyde (bisretinoids) form nonenzymatically in photoreceptor cells and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin; these fluorophores are implicated in the pathogenesis of inherited and age-related macular degeneration (AMD). Here we demonstrate that bisretinoid photodegradation is ongoing in the eye. High-performance liquid chromatography (HPLC) analysis of eyes of dark-reared and cyclic light-reared wild-type mice, together with comparisons of pigmented versus albino mice, revealed a relationship between intraocular light and reduced levels of the bisretinoids A2E and A2-glycero-phosphoethanolamine (A2-GPE). Analysis of the bisretinoids A2E, A2-GPE, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and all-trans-retinal dimer-phosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4(-/-) mice reared in cyclic light compared with darkness. In albino Abca4(-/-) mice receiving a diet supplemented with the antioxidant vitamin E, higher levels of RPE bisretinoid were evidenced by HPLC analysis and quantitation of fundus autofluorescence; this effect is consistent with photooxidative processes known to precede bisretinoid degradation. Amelioration of outer nuclear layer thinning indicated that vitamin E treatment protected photoreceptor cells. Conversely, in-cage exposure to short-wavelength light resulted in reduced fundus autofluorescence, decreased HPLC-quantified A2E, outer nuclear layer thinning, and increased methylglyoxal (MG)-adducted protein. MG was also released upon bisretinoid photodegradation in cells. We suggest that the lower levels of these diretinal adducts in cyclic light-reared and albino mice reflect photodegradative loss of bisretinoid. These mechanisms may underlie associations among AMD risk, oxidative mechanisms, and lifetime light exposure. PMID:27274068

  2. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration

    PubMed Central

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-01-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1−/− mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1−/− mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1−/− mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD. PMID:25604058

  3. Skin Pigmentation Disorders

    MedlinePlus

    ... skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or unhealthy, it affects melanin production. Some pigmentation disorders affect just patches of ...

  4. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    PubMed

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  5. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  6. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  7. Oral pigmentation: A review

    PubMed Central

    Sreeja, C.; Ramakrishnan, K.; Vijayalakshmi, D.; Devi, M.; Aesha, I.; Vijayabanu, B.

    2015-01-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations. PMID:26538887

  8. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  9. Non-invasive in vivo measurement of macular carotenoids

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    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.

  10. Imaging polarimetry of macular disease

    NASA Astrophysics Data System (ADS)

    Miura, Masahiro; Elsner, Ann E.; Petrig, Benno L.; VanNasdale, Dean A.; Zhao, Yanming; Iwasaki, Takuya

    2008-02-01

    Polarization properties of the human eye have long been used to study the tissues of the human retina, as well as to improve retinal imaging, and several new technologies using polarized light are in use or under development. 1-8 The most typical polarimetry technique in ophthalmology clinic is a scanning laser polarimetry for the glaucoma diagnosis. 1,2 In the original conceptualization, the thickness of the retinal nerve fiber layer is estimated using the birefringent component of light returning from the ocular fundus. More recently, customized software to analyze data from scanning laser polarimetry was developed to investigate the polarization properties of the macular disease. 5-8 In this study, we analyzed macular disease with imaging polarimetry, which provides a method for the noninvasive assessment of macular disease.

  11. Overview of plant pigments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chlorophylls, carotenoids, flavonoids and betalains are four major classes of biological pigments produced in plants. Chlorophylls are the primary pigments responsible for plant green and photosynthesis. The other three are accessary pigments and secondary metabolites that yield non-green colors and...

  12. Macular posterior pigmentary incontinence: its relation to macular amyloidosis and notalgia paresthetica.

    PubMed

    Westermark, P; Ridderström, E; Vahlquist, A

    1996-07-01

    Patients with clinical features of dorsal macular amyloidosis but without subepidermal amyloid deposits were followed for 2-11 years. The clinical appearance was fairly stable during this period of time, with little tendency of healing. Only 2 of the patients developed typical macular amyloidosis during the follow-up. It is concluded that a condition strongly resembling macular amyloidosis but without amyloid is an entity, and the designation "macular posterior pigmentary incontinence" is proposed. The relationship between macular posterior pigmentary incontinence and the two conditions macular amyloidosis and notalgia paresthetica is discussed. PMID:8869690

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

    PubMed Central

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

    2011-01-01

    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

  14. Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits.

    PubMed

    Wang, Yong; Zhao, Liang; Lu, Feng; Yang, Xue; Deng, Qianchun; Ji, Baoping; Huang, Fenghong

    2015-01-01

    Excessive visible light exposure can induce damage to retinal cells and contribute to the development or progression of age-related macular degeneration. In this study we created a model of phototoxicity in pigmented rabbits. Furthermore, we investigated the protective effect of bilberry anthocyanin extract (BAE, Table A1) and explored the possible mechanisms of action in this model. The model of light-induced retinal damage was established by the pigmented rabbits exposed to light at 18,000 lx for 2 h, and they were sacrificed on day 7. After administration of BAE at dosages of 250 and 500 mg/kg/day, retinal dysfunction was significantly inhibited in terms of electroretinograms, and the decreased thicknesses of retinal outer nuclear layer and lengths of the outer segments of the photoreceptor cells were suppressed in rabbits with retinal degeneration. BAE attenuated the changes caused by light to certain apoptotic proteins (Bax, Bcl-2, and caspase-3). The extract increased the levels of superoxide dismutase, glutathione peroxidase, and catalase, as well as the total antioxidant capacity, but decreased the malondialdehyde level in the retinal cells. BAE inhibited the light-induced elevation in the levels of proinflammatory cytokines and angiogenic parameters (IL-1β and VEGF). Results showed that visible light-induced retinal degeneration model in pigmented rabbits was successfully established and BAE exhibited protective effects by increasing the antioxidant defense mechanisms, suppressing lipid peroxidation and proinflammatory cytokines, and inhibiting retinal cells apoptosis. PMID:26694327

  15. VITAMIN D DEFICIENCY IN NEOVASCULAR VERSUS NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

    PubMed Central

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W.; Stinnett, Sandra S.; Vajzovic, Lejla M.; Mruthyunjaya, Prithvi

    2014-01-01

    Purpose To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Methods Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Results Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non–age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18– 0.68) odds ratio for NVAMD. Conclusion This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD. PMID:24946100

  16. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    PubMed

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases. PMID:27072643

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

    PubMed

    Allikmets, R; Seddon, J M; Bernstein, P S; Hutchinson, A; Atkinson, A; Sharma, S; Gerrard, B; Li, W; Metzker, M L; Wadelius, C; Caskey, C T; Dean, M; Petrukhin, K

    1999-06-01

    Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category. PMID:10453731

  18. Angiopoietin-like Protein 2 Is a Multistep Regulator of Inflammatory Neovascularization in a Murine Model of Age-related Macular Degeneration*

    PubMed Central

    Hirasawa, Manabu; Takubo, Keiyo; Osada, Hideto; Miyake, Seiji; Toda, Eriko; Endo, Motoyoshi; Umezawa, Kazuo; Tsubota, Kazuo; Oike, Yuichi; Ozawa, Yoko

    2016-01-01

    Choroidal neovascularization (CNV) is a pathogenic process of age-related macular degeneration, a vision-threatening disease. The retinal pigment epithelium and macrophages both influence CNV development. However, the underlying mechanisms remain obscure. Here, we focus on Angptl2 (angiopoietin-like protein 2), a cytokine involved in age-related systemic diseases. Angptl2 was originally identified as an adipocytokine and is also expressed in the eye. Using a laser-induced CNV model, we found that Angptl2 KO mice exhibited suppressed CNV development with reduced macrophage recruitment and inflammatory mediator induction. The mediators monocyte chemotactic protein-1, interleukin-1β (Il-1β), Il-6, matrix metalloprotease-9 (Mmp-9), and transforming growth factor-β1 (Tgf-β1) that were up-regulated during CNV development were all suppressed in the retinal pigment epithelium-choroid of CNV models generated in the Angptl2 KO mice. Bone marrow transplantation using wild-type and KO mice suggested that both bone marrow-derived and host-derived Angptl2 were responsible for macrophage recruitment and CNV development. Peritoneal macrophages derived from Angptl2 KO mice expressed lower levels of the inflammatory mediators. In the wild-type peritoneal macrophages and RAW264.7 cells, Angptl2 induced the mediators via integrins α4 and β2, followed by the downstream activation of NF-κB and ERK. The activation of NF-κB and ERK by Angptl2 also promoted macrophage migration. Therefore, Angptl2 from focal tissue might trigger macrophage recruitment, and that from recruited macrophages might promote expression of inflammatory mediators including Angptl2 in an autocrine and/or paracrine fashion to facilitate CNV development. Angptl2 might therefore represent a multistep regulator of CNV pathogenesis and serve as a new therapeutic target for age-related macular degeneration. PMID:26839315

  19. Macular thickness and macular volume measurements using spectral domain optical coherence tomography in normal Nepalese eyes

    PubMed Central

    Pokharel, Amrit; Shrestha, Gauri Shankar; Shrestha, Jyoti Baba

    2016-01-01

    Purpose To record the normative values for macular thickness and macular volume in normal Nepalese eyes. Methods In all, 126 eyes of 63 emmetropic subjects (mean age: 21.17±6.76 years; range: 10–37 years) were assessed for macular thickness and macular volume, using spectral domain-optical coherence tomography over 6×6 mm2 in the posterior pole. A fast macular thickness protocol was employed. Statistics such as the mean, median, standard deviation, percentiles, and range were used, while a P-value was set at 0.05 to test significance. Results Average macular thickness and total macular volume were larger in males compared to females. With each year of increasing age, these variables decreased by 0.556 μm and 0.0156 mm3 for average macular thickness and total macular volume, respectively. The macular thickness was greatest in the inner superior section and lowest at the center of the fovea. The volume was greatest in the outer nasal section and thinnest in the fovea. The central subfield thickness (r=−0.243, P=0.055) and foveal volume (r=0.216, P=0.09) did not correlate with age. Conclusion Males and females differ significantly with regard to macular thickness and macular volume measurements. Reports by other studies that the increase in axial length reduced thickness and volume, were negated by this study which found a positive correlation among axial length, thickness, and volume. PMID:27041990

  20. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    PubMed Central

    2014-01-01

    A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole. PMID:24949209

  1. Retinal phagocytes in age-related macular degeneration

    PubMed Central

    Kim, Soo-Young

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in industrial countries. Vision loss caused by AMD results from geographic atrophy (dry AMD) and/or choroidal neovascularization (wet AMD). Presently, the etiology and pathogenesis of AMD is not fully understood and there is no effective treatment. Oxidative stress in retinal pigment epithelial (RPE) cells is considered to be one of the major factors contributing to the pathogenesis of AMD. Also retinal glia, as scavengers, are deeply related with diseases and could play a role. Therefore, therapeutic approaches for microglia and Müller glia, as well as RPE, may lead to new strategies for AMD treatment. This review summarizes the pathological findings observed in RPE cells, microglia and Müller glia of AMD murine models. PMID:26052551

  2. Molecular pathology of age-related macular degeneration

    PubMed Central

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

    2009-01-01

    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

  3. [Treatment of serous macular retinal detachment with antihistamines].

    PubMed

    Kirschfeld, K

    2015-01-01

    The etiology of retinal detachment in central serous retinopathy (CSR) is unknown; however, three facts are generally accepted: (1) the serous exudate which raises the layers of the receptors/pigment epithelium is formed due to hyperpermeability in the choriocapillaries, (2) patients frequently suffer from headaches and (3) stress promotes the incidence of CSR. A high blood plasma histamine concentration can cause the abovementioned symptoms which suggests that histamine might provoke CSR. Within 1 week after administration of the antihistamine loratadin a considerable reduction in the retinal exudate and restoration of vision were observed. This supports the hypothesis that histamine could be involved in the process of retinal detachment. Further investigations and large scale clinical trials should clarify if this hypothesis can be proved or disproved and whether antihistamines can be used for age-related macular degeneration (AMD). PMID:25278347

  4. Zinc Deficiency Leads to Lipofuscin Accumulation in the Retinal Pigment Epithelium of Pigmented Rats

    PubMed Central

    Kokkinou, Despina; Eibl, Oliver; Schraermeyer, Ulrich

    2011-01-01

    Background Age-related macular degeneration (AMD) is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. Methodology/Principal Findings Adult Long Evans (LE) rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE) were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX) microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE). The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (Ø>3 µm) found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 µm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4–3 µm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. Conclusions/Significance In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane. PMID:22216222

  5. Identification of spectral phenotypes in age-related macular degeneration patients

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

    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.

  6. RECURRENT CHOROIDAL NEOVASCULARIZATION AFTER MACULAR TRANSLOCATION SURGERY WITH 360-DEGREE PERIPHERAL RETINECTOMY

    PubMed Central

    BAER, CLAXTON A.; RICKMAN, CATHERINE BOWES; SRIVASTAVA, SUNIL; MALEK, GOLDIS; STINNETT, SANDRA; TOTH, CYNTHIA A.

    2012-01-01

    Purpose To evaluate the pattern of age-related macular degeneration in the new foveal location after macular translocation surgery with 360 degree peripheral retinectomy for neovascular age-related macular degeneration. Methods Clinical data, fundus photos, and fluorescein angiograms of patients in the Duke Macular Translocation Study were reviewed with 2-year follow-up data. Results With 56 patients completing follow-up, no patient developed de novo choroidal neovascularization (CNV), geographic atrophy, or drusen in the new subfoveal retinal pigment epithelium bed. By 2 years, 14 patients (25%) developed recurrent CNV and 13 of these 14 recurrences clearly arose from the old CNV bed. Of the 13 recurrences clearly arising from the old bed, 12 of them had recurrent CNV that involved the margin of the bed closest to the repositioned fovea. Smokers were 5.3 times (95% confidence interval: 1.2–24) more likely to develop recurrent CNV over 2 years. Despite treatment, median visual acuity for the 14 eyes with recurrent CNV was 20/200 compared with 20/80 in eyes without recurrence. Conclusions Findings in this study support the hypotheses that the development of CNV occurs via a signaling mechanism from the fovea. PMID:18626416

  7. Laser therapy and macular degeneration

    NASA Astrophysics Data System (ADS)

    Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania

    2001-10-01

    Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.

  8. Nutritional supplements for macular degeneration.

    PubMed

    2006-02-01

    Age-related macular degeneration is the commonest cause of blindness in developed countries and the third most common worldwide. Each year in the UK, around 17,000 people become blind or partially sighted as a result of this condition, and its prevalence is likely to increase with an ageing population. Laser therapy and rarely surgery, can slow disease progression in a minority of patients but is unlikely to restore lost vision. A wide range of nutritional supplements are now on sale with promotional claims that they improve eye health. While some specialists recommend their use to patients with advanced disease, these supplements are also increasingly promoted to people with early or no signs of disease. Consequently, GPs come under pressure from patients to recommend, or even prescribe, a nutritional supplement. Here we examine the evidence for nutritional supplements in the management of age-related macular degeneration and consider which, if any, can be recommended. PMID:16550811

  9. Comparison of macular versus paramacular retinal sensitivity to femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Cain, Clarence P.; Toth, Cynthia A.; Thomas, Robert J.; Noojin, Gary D.; Carothers, Val; Stolarski, David J.; Rockwell, Benjamin A.

    2000-07-01

    Single 130 fs laser pulses in the near-IR (800 nm) were used to create ophthalmoscopically viewed minimum visible lesions (MVLs) within the macular and paramacular regions in rhesus monkey eyes. MVL thresholds at 1 and 24 h are reported as the 50% probability for damage (ED50) together with their fiducial limits at the 95% confidence level. These measured thresholds are compared with previously reported thresholds for near-IR and visible wavelengths for both macular and paramacular areas. Threshold doses were lower at the 24 h reading than at the 1 h reading for both retinal regions and the ED50s for the macular were slightly lower than for the paramacula. We measured the 24 h MVL ED50 thresholds to be 0.35 and 0.55 (mu) J for the macular and paramacular areas, respectively. The combined data for both areas yielded a threshold of 0.45 (mu) J.

  10. Oxidative stress, innate immunity, and age-related macular degeneration

    PubMed Central

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  11. Arginine-Restricted Therapy Resistant Bilateral Macular Edema Associated with Gyrate Atrophy

    PubMed Central

    Doguizi, Sibel; Sekeroglu, Mehmet Ali; Anayol, Mustafa Alpaslan; Yilmazbas, Pelin

    2015-01-01

    Introduction. Gyrate atrophy is a rare genetical metabolic disorder affecting vision. Here, we report a 9-year-old boy with gyrate atrophy associated with bilateral macular edema at the time of diagnosis and the effect of long term metabolic control on macular edema. Case Presentation. A 9-year-old boy presented with a complaint of low visual acuity (best corrected visual acuity: 20/80 in both eyes, refractive error: −12.00 D). Dilated fundus examination revealed multiple bilateral, sharply defined, and scalloped chorioretinal atrophy areas in the midperipheral and peripheral zone. Spectral-domain optical coherence tomography revealed bilateral cystoid macular edema in both eyes. Serum ornithine level was high (622 μmol/L). An arginine-restricted diet reduced serum ornithine level (55 μmol/L). However, visual findings including macular edema remained unchanged in 2 years of follow-up. Conclusion. Arginine-restricted diet did not improve macular edema in our patient with gyrate atrophy. A more comprehensive understanding of the underlying factors for macular edema will lead to the development of effective therapies. PMID:26770854

  12. Classification of wet aged related macular degeneration using optical coherence tomographic images

    NASA Astrophysics Data System (ADS)

    Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

    2013-12-01

    Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

  13. 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.

    PubMed

    Krämer, F; White, K; Pauleikhoff, D; Gehrig, A; Passmore, L; Rivera, A; Rudolph, G; Kellner, U; Andrassi, M; Lorenz, B; Rohrschneider, K; Blankenagel, A; Jurklies, B; Schilling, H; Schütt, F; Holz, F G; Weber, B H

    2000-04-01

    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 32 unrelated patients with adult vitelliform macular dystrophy (AVMD) and 200 patients with age-related macular degeneration (AMD). Both AVMD and AMD share some phenotypic features with Best disease such as abnormal subretinal accumulation of lipofuscin material, progressive geographic atrophy and choroidal neovascularisation, and may be the consequence of a common pathogenic mechanism. In total, we have identified 23 distinct disease-associated mutations in Best disease and four different mutations in AVMD. Two of the mutations found in the AVMD patients were also seen in Best disease suggesting a considerable overlap in the aetiology of these two disorders. There were no mutations found in the AMD group. In addition, four frequent intragenic polymorphisms did not reveal allelic association of the VMD2 locus with AMD. These data exclude a direct role of VMD2 in the predisposition to AMD. PMID:10854112

  14. Plasma Protein Pentosidine and Carboxymethyllysine, Biomarkers for Age-related Macular Degeneration*

    PubMed Central

    Ni, Jiaqian; Yuan, Xianglin; Gu, Jiayin; Yue, Xiuzhen; Gu, Xiaorong; Nagaraj, Ram H.; Crabb, John W.

    2009-01-01

    Age-related macular degeneration (AMD) causes severe vision loss in the elderly; early identification of AMD risk could help slow or prevent disease progression. Toward the discovery of AMD biomarkers, we quantified plasma protein Nε-carboxymethyllysine (CML) and pentosidine from 58 AMD and 32 control donors. CML and pentosidine are advanced glycation end products that are abundant in Bruch membrane, the extracellular matrix separating the retinal pigment epithelium from the blood-bearing choriocapillaris. We measured CML and pentosidine by LC-MS/MS and LC-fluorometry, respectively, and found higher mean levels of CML (∼54%) and pentosidine (∼64%) in AMD (p < 0.0001) relative to normal controls. Plasma protein fructosyl-lysine, a marker of early glycation, was found by amino acid analysis to be in equal amounts in control and non-diabetic AMD donors, supporting an association between AMD and increased levels of CML and pentosidine independent of other diseases like diabetes. Carboxyethylpyrrole (CEP), an oxidative modification from docosahexaenoate-containing lipids and also abundant in AMD Bruch membrane, was elevated ∼86% in the AMD cohort, but autoantibody titers to CEP, CML, and pentosidine were not significantly increased. Compellingly higher mean levels of CML and pentosidine were present in AMD plasma protein over a broad age range. Receiver operating curves indicate that CML, CEP adducts, and pentosidine alone discriminated between AMD and control subjects with 78, 79, and 88% accuracy, respectively, whereas CML in combination with pentosidine provided ∼89% accuracy, and CEP plus pentosidine provided ∼92% accuracy. Pentosidine levels appeared slightly altered in AMD patients with hypertension and cardiovascular disease, indicating further studies are warranted. Overall this study supports the potential utility of plasma protein CML and pentosidine as biomarkers for assessing AMD risk and susceptibility, particularly in combination with CEP

  15. Ion transport in pigmentation

    PubMed Central

    Bellono, Nicholas W.; Oancea, Elena V.

    2014-01-01

    Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system,, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis. PMID:25034214

  16. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  17. Congenital high myopia and central macular atrophy: a report of 3 families

    PubMed Central

    Hull, S; Kalhoro, A; Marr, J; Thompson, D A; Holder, G E; Robson, A G; Moore, A T

    2015-01-01

    Aims To report the clinical phenotype in a series of four children from three families with the rare association of high myopia, central macular atrophy, and normal full-field electroretinography (ERG). Methods Four male patients were ascertained with reduced vision, nystagmus, and atrophy of the macula from early childhood. Patients underwent full ophthalmic examination, electrophysiological testing, and retinal imaging. Results Minimum duration of follow-up was 8 years. At last review, visual acuity ranged from 0.22 to 1.20 logMAR (6/9.5–6/95 Snellen) at a mean age of 10.5 years (median 9.5 years, range 9–14 years). Refractive error ranged from a spherical equivalent of −7.40 D to −24.00 D. Three had convergent squint. Fundus examination and imaging demonstrated bilateral macular atrophy in all patients that varied from mild atrophy of the retinal pigment epithelium (RPE) to well-demarcated, punched-out atrophic lesions of retina, RPE, and choroid. Flash ERG was normal under photopic and scotopic conditions in all patients. Pattern ERG, performed in three patients, was consistent with mild to severe macular dysfunction. Progression of the area of atrophy was evident in one patient and of the myopia in two patients but all patients had stable visual acuity. Conclusions Patients with congenital high myopia and macular atrophy present in infancy with reduced visual acuity and nystagmus. The macular atrophic lesions vary in size and severity but electrophysiological testing is consistent with dysfunction confined to the macula. There was no deterioration in visual acuity over 8–10 years of monitoring. PMID:25998941

  18. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy. PMID:25715554

  19. Visual prosthetic device for bilateral end-stage macular degeneration.

    PubMed

    Chun, Dal W; Heier, Jeffrey S; Raizman, Michael B

    2005-11-01

    Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life. PMID:16293092

  20. Pigment-protein complexes

    SciTech Connect

    Siegelman, H W

    1980-01-01

    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.

  1. Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix metabolism and age-related macular degeneration-like pathology

    PubMed Central

    Hu, Peng; Herrmann, Rolf; Bednar, Amanda; Saloupis, Peter; Dwyer, Mary A.; Yang, Ping; Qi, Xiaoping; Thomas, Russell S.; Jaffe, Glenn J.; Boulton, Michael E.; McDonnell, Donald P.; Malek, Goldis

    2013-01-01

    The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates xenobiotic metabolism and detoxification. Herein, we report a previously undescribed role for the AhR signaling pathway as an essential defense mechanism in the pathogenesis of early dry age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that AhR activity and protein levels in human retinal pigment epithelial (RPE) cells, cells vulnerable in AMD, decrease with age. This finding is significant given that age is the most established risk factor for development of AMD. Moreover, AhR−/− mice exhibit decreased visual function and develop dry AMD-like pathology, including disrupted RPE cell tight junctions, accumulation of RPE cell lipofuscin, basal laminar and linear-like deposit material, Bruch’s membrane thickening, and progressive RPE and choroidal atrophy. High-serum low-density lipoprotein levels were also observed in AhR−/− mice. In its oxidized form, this lipoprotein can stimulate increased secretion of extracellular matrix molecules commonly found in deposits from RPE cells, in an AhR-dependent manner. This study demonstrates the importance of cellular clearance via the AhR signaling pathway in dry AMD pathogenesis, implicating AhR as a potential target, and the mouse model as a useful platform for validating future therapies. PMID:24106308

  2. Protective responses to sublytic complement in the retinal pigment epithelium.

    PubMed

    Tan, Li Xuan; Toops, Kimberly A; Lakkaraju, Aparna

    2016-08-01

    The retinal pigment epithelium (RPE) is a key site of injury in inherited and age-related macular degenerations. Abnormal activation of the complement system is a feature of these blinding diseases, yet how the RPE combats complement attack is poorly understood. The complement cascade terminates in the cell-surface assembly of membrane attack complexes (MACs), which promote inflammation by causing aberrant signal transduction. Here, we investigated mechanisms crucial for limiting MAC assembly and preserving cellular integrity in the RPE and asked how these are compromised in models of macular degeneration. Using polarized primary RPE and the pigmented Abca4(-/-) Stargardt disease mouse model, we provide evidence for two protective responses occurring within minutes of complement attack, which are essential for maintaining mitochondrial health in the RPE. First, accelerated recycling of the membrane-bound complement regulator CD59 to the RPE cell surface inhibits MAC formation. Second, fusion of lysosomes with the RPE plasma membrane immediately after complement attack limits sustained elevations in intracellular calcium and prevents mitochondrial injury. Cholesterol accumulation in the RPE, induced by vitamin A dimers or oxidized LDL, inhibits these defense mechanisms by activating acid sphingomyelinase (ASMase), which increases tubulin acetylation and derails organelle traffic. Defective CD59 recycling and lysosome exocytosis after complement attack lead to mitochondrial fragmentation and oxidative stress in the RPE. Drugs that stimulate cholesterol efflux or inhibit ASMase restore both these critical safeguards in the RPE and avert complement-induced mitochondrial injury in vitro and in Abca4(-/-) mice, indicating that they could be effective therapeutic approaches for macular degenerations. PMID:27432952

  3. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956

  4. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

    Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition. PMID:24860651

  5. C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration (AMD)

    PubMed Central

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

    2016-01-01

    Background There 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 complement factor H (CFH) gene and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have been consistently shown to be associated with an increased risk for AMD. In the present study, we examined the immunolocalization of CRP and CFH in aged control human donor eyes (n=10; mean age 79 yrs) and eyes with AMD (n=18; mean age 83 yrs). Methods Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against CRP and CFH on cryopreserved tissue sections from disc/macular blocks. Three independent masked observers scored the reaction product (0-8). Results In aged control eyes, the retinal pigment epithelium/Bruch’s membrane/choriocapillaris (RPE/BrM/CC) complex including intercapillary septa (ICS) had the most prominent immunostaining for CRP and CFH. CRP was significantly higher than controls in BrM/CC/ICS and choroidal stroma in early and wet AMD eyes (p<0.05). In contrast, CFH was significantly lower in BrM/CC/ICS complex of AMD choroids than in controls (p<0.05). Interestingly, CRP and CFH were significantly reduced in BrM/CC/ICS complex in atrophic area of macula in geographic atrophy (GA)(p<0.05). Drusen and basal laminar deposits were intensely positive for CRP and CFH. Conclusion These immunohistochemical findings show that changes in distribution and relative levels of CRP and CFH were evident in early and late AMD eyes. This suggests that high levels of CRP and insufficient CFH at the retina/choroid interface may lead to uncontrolled complement activation with associated cell and tissue damage. This study supports the hypothesis that inflammation and immune-mediated mechanisms are involved in the pathogenesis of AMD. PMID:21633121

  6. Quantitative Fundus Autofluorescence and Optical Coherence Tomography in Best Vitelliform Macular Dystrophy

    PubMed Central

    Duncker, Tobias; Greenberg, Jonathan P.; Ramachandran, Rithambara; Hood, Donald C.; Smith, R. Theodore; Hirose, Tatsuo; Woods, Russell L.; Tsang, Stephen H.; Delori, François C.; Sparrow, Janet R.

    2014-01-01

    Purpose. Quantitative fundus autofluorescence (qAF), spectral domain optical coherence tomography (SD-OCT) segmentation, and multimodal imaging were performed to elucidate the pathogenesis of Best vitelliform macular dystrophy (BVMD) and to identify abnormalities in lesion versus nonlesion fundus areas. Methods. Sixteen patients with a clinical diagnosis of BVMD were studied. Autofluorescence images (30°, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The grey levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density, to yield qAF. Horizontal SD-OCT scans were obtained and retinal layers manually segmented. Additionally, color and near-infrared reflectance (NIR-R) images were registered to AF images. All patients were screened for mutations in BEST1. In three additional BVMD patients, in vivo spectrofluorometric measurements were obtained within the vitelliform lesion. Results. Mean nonlesion qAF was within normal limits for age. Maximum qAF within the lesion was markedly increased compared with controls. By SD-OCT segmentation, outer segment equivalent thickness was increased and outer nuclear layer thickness decreased in the lesion. Changes were also present in a transition zone beyond the lesion border. In subclinical patients, no abnormalities in retinal layer thickness were identified. Fluorescence spectra recorded from the vitelliform lesion were consistent with those of retinal pigment epithelial cell lipofuscin. Conclusions. Based on qAF, mutations in BEST1 do not cause increased lipofuscin levels in nonlesion fundus areas. PMID:24526438

  7. Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells.

    PubMed

    Ferrington, Deborah A; Tran, Tina N; Lew, Kathleen L; Van Remmen, Holly; Gregerson, Dale S

    2006-09-01

    Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent role in several retinal degenerative diseases, such as age-related macular degeneration, and with light damage. Strategies for preservation of vision that would interrupt the apoptotic cascade require understanding the molecular events associated with apoptosis. This study investigated the susceptibility of RPE to caspase-dependent and -independent apoptotic pathways when challenged with different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from wildtype and heterozygous mice with reduced levels of either Mn superoxide dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis through both caspase-independent and -dependent pathways, respectively. With both oxidants, translocation of apoptosis inducing factor into the nucleus was observed. Cells containing reduced levels of CuZnSOD were the most susceptible to oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas death receptor induced caspase-dependent apoptosis. These results show stimulus-specific activation of either the caspase-dependent or -independent pathway. Since cultured RPE express the protein components required for different apoptotic pathways, they provide a good model system for studying molecular events associated with multiple signals that lead to cell death. PMID:16682026

  8. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration.

    PubMed

    Schmidt-Erfurth, Ursula; Waldstein, Sebastian M

    2016-01-01

    Neovascular age-related macular degeneration (AMD) has undergone substantial break-throughs in diagnostic as well as therapeutic respect, with optical coherence tomography (OCT) allowing to identify disease morphology in great detail, and intravitreal anti-vascular endothelial growth factor therapy providing unprecedented benefit. However, these two paths have yet not been combined in an optimal way, real-world outcomes are inferior to expectations, and disease management is largely inefficient in the real-world setting. This dilemma can be solved by identification of valid biomarkers relevant for visual function, disease activity and prognosis, which can provide solid guidance for therapeutic management on an individual level as well as on the population base. Qualitative and quantitative morphological features obtained by advanced OCT provide novel insight into exudative and degenerative stages of neovascular AMD. However, conclusions from structure/function correlations evolve differently from previous paradigms. While central retinal thickness was used as biomarker for guiding retreatment management in clinical trials and practice, fluid localization in different compartments offers superior prognostic value: Intraretinal cystoid fluid has a negative impact on visual acuity and is considered as degenerative when persisting through the initial therapeutic interval. Subretinal fluid is associated with superior visual benefit and a lower rate of progression towards geographic atrophy. Detachment of the retinal pigment epithelium was identified as most pathognomonic biomarker, often irresponsive to therapy and responsible for visual decline during a pro-re-nata regimen. Alterations of neurosensory tissue are usually associated with irreversible loss of functional elements and a negative prognosis. Novel OCT technologies offer crucial insight into corresponding changes at the level of the photoreceptor--retinal pigment epithelial--choriocapillary unit, identifying

  9. Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration.

    PubMed

    Singh, Ruchira; Kuai, David; Guziewicz, Karina E; Meyer, Jackelyn; Wilson, Molly; Lu, Jianfeng; Smith, Molly; Clark, Eric; Verhoeven, Amelia; Aguirre, Gustavo D; Gamm, David M

    2015-11-01

    Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is essential for vision, and studies have implicated altered POS processing in the pathogenesis of some retinal degenerative diseases. Consistent with this concept, a recently established hiPSC-RPE model of inherited macular degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein we utilized this model to determine (i) if disturbances in protein degradation pathways are associated with delayed POS digestion and (ii) whether such defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures possessed increased protein oxidation, decreased free-ubiquitin levels, and altered rates of exosome secretion, consistent with altered POS processing. Application of valproic acid (VPA) with or without rapamycin increased rates of POS degradation in our model, whereas application of bafilomycin-A1 decreased such rates. Importantly, the negative effect of bafilomycin-A1 could be fully reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident following examination of its efficacy and metabolism in a complementary canine disease model. Our findings suggest that disturbances in protein degradation pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which can be manipulated pharmacologically. These results have therapeutic implications for BD and perhaps other maculopathies. PMID:26300224

  10. Analysis of candidate genes for macular telangiectasia type 2

    PubMed Central

    Parmalee, Nancy L.; Schubert, Carl; Merriam, Joanna E.; Allikmets, Kaija; Bird, Alan C.; Gillies, Mark C.; Peto, Tunde; Figueroa, Maria; Friedlander, Martin; Fruttiger, Marcus; Greenwood, John; Moss, Stephen E.; Smith, Lois E.H.; Toomes, Carmel; Inglehearn, Chris F.

    2010-01-01

    Purpose To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach. Methods Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they co-segregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts. Results We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism. Conclusions We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel. PMID:21179236

  11. Fuzzy logic for identifying pigments studied by Raman spectroscopy.

    PubMed

    Ramos, Pablo Manuel; Ferré, Joan; Ruisánchez, Itziar; Andrikopoulos, Konstantinos S

    2004-07-01

    Fuzzy logic and linguistic variables are used for the automatic interpretation of Raman spectra obtained from pigments found in cultural heritage art objects. Featured bands are extracted from a Raman spectrum of a reference pigment and the methodology for constructing the library is illustrated. An unknown spectrum is then interpreted automatically and a process for identifying the corresponding pigment is described. A reference library consisting of 32 pigments was built and the effectiveness of the algorithm was tested by the Raman spectroscopic analysis of 10 pigments that are known to have been extensively used in Byzantine hagiography. Binary mixtures of these pigments were also tested. The algorithm's level of identification was good even though extra peaks, noise, and background signals were encountered in the spectra. PMID:15282052

  12. Flicker fusion thresholds in Best macular dystrophy.

    PubMed

    Massof, R W; Fleischman, J A; Fine, S L; Yoder, F

    1977-06-01

    Flicker fusion threshold intensities were measured as a function of flicker frequency for patients with Best macular dystrophy having normal or near-normal Snellen visual acuity. These data were found to differ from normal in ways that may be interpreted to be an abnormal elevation of the foveal cone threshold, a loss of cone temporal resolution, or both. The results led to the conclusion that Best macular dystrophy affects the neurosensory retina even when Snellen visual acuity is normal. PMID:869758

  13. Three-Month Outcome of Ziv-Aflibercept for Diabetic Macular Edema

    PubMed Central

    Marashi, Ameen

    2016-01-01

    Purpose Is to show the 3-month efficacy and safety of treatment diabetic macular edema treated with intravitreal ziv-aflibercept as studies have shown that Ziv-aflibercept does not cause retinal pigment epithelial toxicity and to study it cost effectiveness. Methods Ten eyes in eight patients diagnosed with central diabetic macular edema were enrolled for three consecutive intravitreal injection of ziv-aflibercept 1.25 mg every 4 weeks, a complete exam including BCVA and CRT at baseline and 12 weeks with evaluation of ocular and systemic complications. Results Improvement of best corrected visual acuity was clinically significant from baseline LogMAR 0.77 and 0.35 at 12 weeks and statistically significant (P<0.05) along with reduction of central retinal thickness from 562,4 μm and 317.7 μm at 12 weeks follow up (P<0.05) with no signs of ocular nor systemic complications. Conclusion Ziv aflibercept is a safe and effective in diabetic macular edema treatment for 12 weeks follow up with cost effectiveness especially in countries where aflibercept is not available. PMID:27347566

  14. The mystery of angiographically silent macular oedema due to taxanes.

    PubMed

    Kuznetcova, Tatiana I; Cech, Petr; Herbort, Carl P

    2012-06-01

    Taxanes are widely used anticancer agents, produced from the plants of the genus Taxus (yews). One of the rare side-effects caused by taxanes is a bilateral cystoid macular oedema (CMO). The particularity of this type of CMO is that it is angiographically silent showing no leakage or pooling on fluorescein angiography (FA). To date, the mechanism of this oedema has not been clearly understood and existing theories do not explain this phenomenon very well. Our aim was to report a case of paclitaxel-induced CMO and put forward a putative explanation for this occurrence. A 64-year-old woman presented with a 7-month history of progressively decreasing bilateral visual acuity with an apparently normal fundus. At entry her best-corrected visual acuity (BCVA) was 0.4 for far and near OD and 0.5 for far and near OS. Optical coherence tomography (OCT) revealed a CMO with a central thickness of 561 μm OD and 488 μm OS; there were no signs of intraocular inflammation. FA showed no capillary leakage and quasi absent late hyperfluorescence OU. Indocyanine green angiography was within normal limits. Classical CMO treatment was ineffective and only discontinuation of paclitaxel resulted in recovery of a normal macular structure after 4 weeks with an increase of BCVA to 0.9 OD and 1.0 OS. In order to understand the properties of taxane drug-induced cystoid macular oedema (TDICMO) we compared the spectral OCT findings of our case to an inflammation-induced CMO of equal thickness and to a case of multifocal choroiditis. The plane of separation of TDICMO was above the external limiting membrane in both cases. In contrast to inflammation-induced CMO where the four external bands were well identified, there was attenuation of these bands in TDICMO but no disruption of the layers as seen in multifocal choroiditis, indicating that the fluid in TDICMO had a high viscosity producing a shadow underneath. TDICMO most probably originates from retinal pigment epithelium dysfunction by their

  15. Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study.

    PubMed

    Koh, Hui-Hiang; Murray, Ian J; Nolan, Daniel; Carden, Dave; Feather, Jim; Beatty, Stephen

    2004-07-01

    There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM. PMID:15183097

  16. Biology of pigmentation

    SciTech Connect

    Parker, F.

    1981-01-01

    The many factors involved in the normal pigmentation of human skin are highly complex involving anatomic, biochemical, and genetic aspects of melanocytes in the skin and the influence of UV light and various hormones on the melanocytes. It is probably more than just coincidence that the melanocytes, which are of neurogenic origin, are so responsive to several trophic hormones produced in the brain. Understanding of the various factors involved in the normal pigmentary process is crucial to explaining the many alterations and anomalies in human pigmentation.

  17. Age-related macular degeneration and changes in the extracellular matrix

    PubMed Central

    Nita, Małgorzata; Strzałka-Mrozik, Barbara; Grzybowski, Andrzej; Mazurek, Urszula; Romaniuk, Wanda

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of permanent, irreversible, central blindness (scotoma in the central visual field that makes reading and writing impossible, stereoscopic vision, recognition of colors and details) in patients over the age of 50 years in European and North America countries, and an important role is attributed to disorders in the regulation of the extracellular matrix (ECM). The main aim of this article is to present the crucial processes that occur on the level of Bruch’s membrane, with special consideration of the metalloproteinase substrates, metalloproteinase, and tissue inhibitor of metalloproteinase (TIMP). A comprehensive review of the literature was performed through MEDLINE and PubMed searches, covering the years 2005–2012, using the following keywords: AMD, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases, Bruch’s membrane, collagen, elastin. In the pathogenesis of AMD, a significant role is played by collagen type I and type IV; elastin; fibulin-3, -5, and -6; matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, and MMP-1; and TIMP-3. Other important mechanisms include: ARMS2 and HTR1 proteins, the complement system, the urokinase plasminogen activator system, and pro-renin receptor activation. Continuous rebuilding of the extracellular matrix occurs in both early and advanced AMD, simultaneously with the dysfunction of retinal pigment epithelium (RPE) cells and endothelial cells. The pathological degradation or accumulation of ECM structural components are caused by impairment or hyperactivity of specific MMPs/TIMPs complexes, and is also endangered by the influence of other mechanisms connected with both genetic and environmental factors. PMID:24938626

  18. Regulation of age-related macular degeneration-like pathology by complement factor H

    PubMed Central

    Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/− and Cfh−/− mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/− and Cfh−/− mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/− mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/− mice versus complement deficiency in Cfh−/− animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

  19. UV-induced retinal proteome changes in the rat model of age-related macular degeneration.

    PubMed

    Kraljević Pavelić, Sandra; Klobučar, Marko; Sedić, Mirela; Micek, Vedran; Gehrig, Peter; Grossman, Jonas; Pavelić, Krešimir; Vojniković, Božidar

    2015-09-01

    Age-related macular degeneration (AMD) is characterized by irreversible damage of photoreceptors in the central posterior part of the retina, called the macula and is the most common cause of vision loss in those aged over 50. A growing body of evidence shows that cumulative long-term exposure to UV radiation may be harmful to the retina and possibly leads to AMD irrespective of age. In spite of many research efforts, cellular and molecular mechanisms leading to UV-induced retinal damage and possibly retinal diseases such as AMD are not completely understood. In the present study we explored damage mechanisms accounting for UV-induced retinal phototoxicity in the rats exposed to UVA and UVB irradiation using a proteomics approach. Our study showed that UV irradiation induces profound changes in the retinal proteomes of the rats associated with the disruption of energy homeostasis, oxidative stress, DNA damage response and structural and functional impairments of the interphotoreceptor matrix components and their cell surface receptors such as galectins. Two small leucine-rich proteoglycans, biglycan and lumican, were identified as phototoxicity biomarkers associated with UV-induced disruption of interphotoreceptor matrix (IPM). In addition, UVB induced activation of Src kinase, which could account for cytoskeletal rearrangements in the retina was observed at the proteomics level. Pharmacological intervention either to target Src kinase with the aim of preventing cytoskeletal rearrangements in the retinal pigment epithelium (RPE) and neuronal retina or to help rebuild damaged IPM may provide fresh avenues of treatment for patients suffering from AMD. PMID:26071645

  20. Pigments in avocado tissue and oil.

    PubMed

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

    2006-12-27

    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

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

    PubMed

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

    2005-03-15

    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 mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness. PMID:15749821

  2. Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis

    PubMed Central

    Liu, Jian; Copland, David A.; Theodoropoulou, Sofia; Chiu, Hsi An Amy; Barba, Miriam Durazo; Mak, Ka Wang; Mack, Matthias; Nicholson, Lindsay B.; Dick, Andrew D.

    2016-01-01

    Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2+ monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development. PMID:26847702

  3. A2E and lipofuscin distributions in macaque retinal pigment epithelium are similar to human.

    PubMed

    Pallitto, Patrick; Ablonczy, Zsolt; Jones, E Ellen; Drake, Richard R; Koutalos, Yiannis; Crouch, Rosalie K; Donello, John; Herrmann, Julia

    2015-10-01

    The accumulation of lipofuscin, an autofluorescent aging marker, in the retinal pigment epithelium (RPE) has been implicated in the development of age-related macular degeneration (AMD). Lipofuscin contains several visual cycle byproducts, most notably the bisretinoid N-retinylidene-N-retinylethanolamine (A2E). Previous studies with human donor eyes have shown a significant mismatch between lipofuscin autofluorescence (AF) and A2E distributions. The goal of the current project was to examine this relationship in a primate model with a retinal anatomy similar to that of humans. Ophthalmologically naive young (<10 years., N = 3) and old (>10 years., N = 4) Macaca fascicularis (macaque) eyes, were enucleated, dissected to yield RPE/choroid tissue, and flat-mounted on indium-tin-oxide-coated conductive slides. To compare the spatial distributions of lipofuscin and A2E, fluorescence and mass spectrometric imaging were carried out sequentially on the same samples. The distribution of lipofuscin fluorescence in the primate RPE reflected previously obtained human results, having the highest intensities in a perifoveal ring. Contrarily, A2E levels were consistently highest in the periphery, confirming a lack of correlation between the distributions of lipofuscin and A2E previously described in human donor eyes. We conclude that the mismatch between lipofuscin AF and A2E distributions is related to anatomical features specific to primates, such as the macula, and that this primate model has the potential to fill an important gap in current AMD research. PMID:26223373

  4. Evidence for Baseline Retinal Pigment Epithelium Pathology in the Trp1-Cre Mouse

    PubMed Central

    Thanos, Aristomenis; Morizane, Yuki; Murakami, Yusuke; Giani, Andrea; Mantopoulos, Dimosthenis; Kayama, Maki; Roh, Mi In; Michaud, Norman; Pawlyk, Basil; Sandberg, Michael; Young, Lucy H.; Miller, Joan W.; Vavvas, Demetrios G.

    2012-01-01

    The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies. PMID:22429967

  5. Apr3 accelerates the senescence of human retinal pigment epithelial cells.

    PubMed

    Han, Song; Lu, Qingjun; Wang, Ningli

    2016-04-01

    Senescence of retinal pigment epithelium (RPE) cells is a major contributor to age‑related macular degeneration (AMD). However, the molecular mechanisms underlying RPE dysfunction are not well understood. Apoptosis related protein 3 (Apr3) was originally cloned from HL‑60 cells induced by all‑trans retinoic acid (ATRA). Preliminary data revealed elevated Apr3 expression in the tissues of aged mice, suggesting that it is involved in the aging process. The present study demonstrated that Apr3 mRNA and protein levels were markedly increased in aged mouse RPE cells. Elevated Apr3 expression was also observed during premature senescence induced by oxidative stress (H2O2 and tert‑BHP) in ARPE‑19 cells. Moreover, Apr3 overexpression promoted cellular senescence in ARPE‑19 cells, as characterized by enhanced senescence‑associated β‑galactosidase activity, reduced cell proliferation and increased expression of the senescence markers p53 and p21. In addition, it was demonstrated that overexpression of Apr3‑N, a truncated counterpart of Apr3, abrogated Apr3‑induced phenotypes. It was concluded that Apr3 expression was induced in replicative and premature senescence of RPE cells and its overexpression accelerated senescence of ARPE‑19 cells, which provides important insights into the function of Apr3 in senescence‑associated diseases. PMID:26934949

  6. The effect of retinal pigment epithelial cell patch size on growth factor expression

    SciTech Connect

    Vargis, Elizabeth A.; Peterson, Cristen B.; Morrell-Falvey, Jennifer L.; Retterer, Scott T.; Collier, Charles Patrick

    2014-01-30

    The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function that occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.

  7. The effect of retinal pigment epithelial cell patch size on growth factor expression

    DOE PAGESBeta

    Vargis, Elizabeth A.; Peterson, Cristen B.; Morrell-Falvey, Jennifer L.; Retterer, Scott T.; Collier, Charles Patrick

    2014-01-30

    The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function thatmore » occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. As a result, up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.« less

  8. Controlling Retinal Pigment Epithelial Cell Patch Size Influences Growth Factor Expression

    DOE PAGESBeta

    Vargis, Elizabeth A; Peterson, Cristen B; Morrell-Falvey, Jennifer L; Retterer, Scott T; Collier, Pat

    2014-01-01

    The spatial organization of retinal pigment epithelial (RPE) cells grown in culture was controlled using micropatterning techniques in order to examine the effect of patch size on cell health and differentiation. Understanding this effect is a critical step in the development of multiplexed high throughput fluidic assays and provides a model for replicating disease states associated with the deterioration of retinal tissue during age-related macular degeneration (AMD). Microcontact printing of fibronectin on polystyrene and glass substrates was used to promote cell attachment, forming RPE patches of controlled size and shape. These colonies mimic the effect of atrophy and loss-of-function thatmore » occurs in the retina during degenerative diseases such as AMD. After 72 hours of cell growth, levels of vascular endothelial growth factor (VEGF), an important biomarker of AMD, were measured. Cells were counted and morphological indicators of cell viability and tight junction formation were assessed via fluorescence microscopy. Up to a twofold increase of VEGF expression per cell was measured as colony size decreased, suggesting that the local microenvironment of, and connections between, RPE cells influences growth factor expression leading to the initiation and progression of diseases such as AMD.« less

  9. Pathological Consequences of Long-Term Mitochondrial Oxidative Stress in the Mouse Retinal Pigment Epithelium

    PubMed Central

    Seo, Soo-jung; Krebs, Mark P.; Mao, Haoyu; Jones, Kyle; Conners, Mandy; Lewin, Alfred S.

    2012-01-01

    Oxidative stress in the retinal pigment epithelium (RPE) is hypothesized to be a major contributor to the development of age-related macular degeneration (AMD). Mitochondrial manganese superoxide dismutase (MnSOD) is a critical antioxidant protein that scavenges the highly reactive superoxide radical. We speculated that specific reduction of MnSOD in the RPE will increase the level of reactive oxygen species in the retina/RPE/choroid complex leading to pathogenesis similar to geographic atrophy. To test this hypothesis, an Sod2-specific hammerhead ribozyme (Rz), delivered by AAV2/1 and driven by the human VMD2 promoter was injected subretinally into C57BL/6J mice. Dark-adapted full field electroretinogram (ERG) detected a decrease in the response to light. We investigated the age-dependent phenotypic and morphological changes of the outer retina digital fundus imaging and SD-OCT measurement of ONL thickness. Fundus microscopy revealed pigmentary abnormalities in the retina and these corresponded to sub-retinal and sub-RPE deposits seen in SD-OCT B-scans. Light and electron microscopy documented the localization of apical deposits and thickening of the RPE. In RPE flat-mounts we observed abnormally displaced nuclei and regions of apparent fibrosis in the central retina of the oldest mice. This region was surrounded by enlarged and irregular RPE cells that have been observed in eyes donated by AMD patients and in other mouse models of AMD. PMID:22687918

  10. An Improved Method for Extraction and Separation of Photosynthetic Pigments

    ERIC Educational Resources Information Center

    Katayama, Nobuyasu; Kanaizuka, Yasuhiro; Sudarmi, Rini; Yokohama, Yasutsugu

    2003-01-01

    The method for extracting and separating hydrophobic photosynthetic pigments proposed by Katayama "et al." ("Japanese Journal of Phycology," 42, 71-77, 1994) has been improved to introduce it to student laboratories at the senior high school level. Silica gel powder was used for removing water from fresh materials prior to extracting pigments by a…