Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys

Julien, Sylvie; Schraermeyer, Ulrich

doi:10.1016/j.neurobiolaging.2011.12.009

Cited by 42 publications

(43 citation statements)

References 33 publications

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“…However, other in vivo studies (summarized by Katz (2002)), suggest otherwise. Furthermore, a reported decrease in A2-E administered to cultured human RPE cells (Schutt et al, 2007) and a recent report that a pharmacological intervention can decrease the RPE lipofuscin content in monkeys (Julien and Schraermeyer, 2012), also points in that direction. Our observation of a limited decrease in LLAF after stopping the treatment is, to the best of our knowledge, the first direct quantitative observation of this phenomenon.…”

Section: Discussionmentioning

confidence: 89%

Formation of lipofuscin-like material in the RPE Cell by different components of rod outer segments

Lei

Tzekov

McDowell

et al. 2013

Experimental Eye Research

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The mechanisms that control the natural rate of lipofuscin accumulation in the retinal pigment epithelial (RPE) cell and its stability over time are not well understood. Similarly, the contributions of retinoids, phospholipids and oxidation to the rate of accumulation of lipofuscin are uncertain. The experiments in this study were conducted to explore the individual contribution of rod outer segments (ROS) components to lipofuscin formation and its accumulation and stability over time. During the period of 14 days incubation of ROS, lipofuscin-like autofluorescence (LLAF) determined at two wavelengths (530 and 585 nm) by fluorescence-activated cell sorting (FACS) was measured from RPE cells. The autofluorescence increased in an exponential manner with a strong linear component between days 1 and 7. The magnitude of the increase was larger in cells incubated with 4-hydroxynonenal (HNE-ROS) compared with cells incubated with either bleached or unbleached ROS, but with a different spectral profile. A small (10–15%) decrease in LLAF was observed after stopping the ROS feeding for 14 days. The phagocytosis rate of HNE-ROS was higher than that of either bleached or unbleached ROS during the first 24 h of supplementation. Among the different ROS components, the increase of LLAF was highest in cells incubated with all-trans-retinal. Surprisingly, incubation with 11-cis-retinal and 9-cis-retinal also resulted in strong LLAF increase, comparable to the increase induced by all-trans-retinal. Supplementation with liposomes containing phosphatidylethanolamine (22: 6-PE) and phosphatidylcholine (18:1-PC) also increased LLAF, while incubation with opsin had little effect. Cells incubated with retinoids demonstrated strong dose-dependence in LLAF increase, and the magnitude of the increase was 2–3 times higher at 585 nm compared to 530 nm, while cells incubated with liposomes showed little dose-dependence and similar increase at both wavelengths. Very little difference in LLAF was noted between cells incubated with either unbleached or bleached ROS under any conditions. In summary, results from this study suggest that supplementation with various ROS components can lead to an increase in LLAF, although the autofluorescence generated by the different classes of components has distinct spectral profiles, where the autofluorescence induced by retinoids results in a spectral profile closest to the one observed from human lipofuscin. Future fluorescence characterization of LLAF in vitro would benefit from an analysis of multiple wavelengths to better match the spectral characteristics of lipofuscin in vivo.

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Section: Discussionmentioning

confidence: 89%

Formation of lipofuscin-like material in the RPE Cell by different components of rod outer segments

Lei

Tzekov

McDowell

et al. 2013

Experimental Eye Research

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“…Several inhibitors of the visual cycle have been tested, but they cause night-blindness, which may be uncomfortable for the patients, and retinoid-based compounds can cause significant systemic effects and teratogenicity [80,81,82]. Other therapeutic strategies targeting RPE bisretinoids such as scavengers of all- trans -retinal [83], or molecules able to degrade [34] or remove A2E from RPE cells [84,32] have been proposed, but additional research is required to demonstrate their safety and efficacy in humans. Lutein and zeaxanthin, which are naturally present in the human macula, decreased A2E levels in RPE of Japanese quails after 16 weeks of supplementation [36].…”

Section: Discussionmentioning

confidence: 99%

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

et al. 2016

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The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle) in the retinal pigment epithelium (RPE) is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9’-cis-Norbixin (a natural diapocarotenoid, 97% purity) was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201) with 9’-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.

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“…However, increased deposition of lipofuscin in the retinal pigment epithelium is associated with the pathogenesis of age-related macular degeneration, and molecules that decrease lipofuscin in the retinal pigment epithelium may have a potential therapeutic role for this degenerative process. 26 Interestingly, the levels of lipofuscin from the olfactory lobes of the European lobster (Homarus gammarus) have been used as an age predictor for these crustaceans and for other marine animals. 27 …”

Section: Lipochromes (Lipofuscin)mentioning

confidence: 99%

Human Colors—The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

Piña‐Oviedo¹,

Ortíz-Hidalgo²,

Ayala

2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. Objectives.— To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? Data Sources.— Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. Conclusions.— Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a “routine grossing day” with a different perspective.

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Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys

Cited by 42 publications

References 33 publications

Formation of lipofuscin-like material in the RPE Cell by different components of rod outer segments

Formation of lipofuscin-like material in the RPE Cell by different components of rod outer segments

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

Human Colors—The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

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