Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration.

Holz, Frank G.; Bellman, Caren; Staudt, Stephanie; Schütt, F.; Völcher, H.E

doi:10.1016/s0002-9394(01)01394-0

Cited by 249 publications

(319 citation statements)

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“…RPE dysfunction in the macula, whether caused by local environmental insults and/or genetic defect(s), would have a profound impact on the overlying photoreceptors and, therefore, on central vision. However, the nature of the insult(s) that causes RPE dysfunction has yet to be ascertained, although a variety of hypotheses has been advanced over the years including genetic factors, ischemia, oxidative stress, phagocytic overload, cigarette smoke, lipofuscin toxicity and, most recently, microbial infection (127)(128)(129)(130)(131)(132)(133).…”

Section: Morphological Correlates Of Early Amdmentioning

confidence: 99%

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

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Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden.Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene-which encodes the major inhibitor of the complement alternative pathway-is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan.

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Section: Morphological Correlates Of Early Amdmentioning

confidence: 99%

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

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“…The excessive formation of these compounds in Stargardt macular degeneration, is considered to be the cause of a loss of RPE cells in recessive Stargardt disease, a blinding macular disorder of juvenile onset and probably also contributes to the etiology of age-related macular degeneration (AMD), a common cause of blindness in elderly people (Delori et al, 2001;Holz et al, 2001;Radu et al, 2005;Schmitz-Valckenberg et al, 2004;Scholl et al, 2004). Photochemical reactions initiated by excitation from the blue region of the spectrum may contribute to the adverse effects of lipofuscin accumulation.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms involved in A2E oxidation

Kim

Jockusch

Itagaki

et al. 2008

Experimental Eye Research

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A2E is one of the bis-retinoid pyridinium compounds that accumulate as lipofuscin pigments in retinal pigment epithelial (RPE) cells in association with aging and in some inherited forms of retinal degeneration. Here we observed that 430 nm irradiation of A2E in the presence of the spin trap DMPO, led to the appearance of a superoxide dismutase-inhibitable electron paramagnetic resonance (EPR) spectrum characteristic of DMPO-OH; this finding was indicative of hydroxyl radical (OH) formation following initial spin trapping of superoxide anion by DMPO. We also observed an increase in dihydroethidium (HEt) fluorescence and luminol-based chemiluminescence that on the basis of inhibition by superoxide dismutase, was indicative of superoxide anion generation when A2E was irradiated at 430 nm in cell-free systems. Nevertheless, while A2E was readily oxidized in the presence of a singlet oxygen generator, superoxide anion did not serve to oxidize A2E. Specifically, by HPLC quantitation and FAB-mass spectroscopy, there was no evidence of A2E oxidation when A2E was incubated with a superoxide anion generator (xanthine/xanthine oxidase) in a variety of solvents (100% PBS, 30% DMSO in PBS, 100% MeOH and CHCl 3 ) or in the presence of detergent. On the other hand, however, peroxy-A2E, an oxidized form of A2E with an endoperoxide moiety on the short-arm of the molecule, readily underwent further oxygen addition when incubated with xanthine/xanthine oxidase. Superoxide anion may be generated by irradiation of A2E but is not involved in the early events that oxidize A2E. Superoxide can contribute to the further oxidation of already-oxidized A2E.

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“…Geographic atrophy (GA), one of the common features of AMD, involves the progressive loss of the retinal photoreceptors and the RPE cells, as well as atrophy of the underlying CC and choroidal vessels (4)(5)(6). GA regional identification is typically accomplished using autofluorescence imaging techniques, which depend on lipofuscin accumulation within RPE cells associated with this disease, but the current clinical imaging methods are limited in detecting early morphological changes in the choriocapillaris (7,8). An improved understanding of the progression of GA and its underlying mechanisms is important to develop potential therapeutic targets for intervention, and diagnostic tools capable of observing the key features of atrophic AMD are critical for fulfilling this goal.…”

mentioning

confidence: 99%

Optical imaging of the chorioretinal vasculature in the living human eye

Kim

Fingler

Zawadzki

et al. 2013

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

181

119

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Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler's and Haller's layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression. ocular circulation | ocular vasculature | optical angiography | ophthalmic imaging | Fourier-domain optical coherence tomography

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Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration.

Cited by 249 publications

References 0 publications

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

Mechanisms involved in A2E oxidation

Optical imaging of the chorioretinal vasculature in the living human eye

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