Cytotoxicity of All‐<i>Trans</i>‐Retinal Increases Upon Photodegradation<sup>†</sup>

Rozanowska, Malgorzata Barbara; Handzel, Kinga Elzbieta; Boulton, Michael E.; Rozanowski, Bartosz

doi:10.1111/j.1751-1097.2012.01161.x

Cited by 33 publications

(59 citation statements)

References 45 publications

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“…Retinaldehyde 44 and A2E 45 have been shown, in culture, to induce greater cell death upon light exposure. We did not investigate the contribution of light.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells

Mihai

Washington

2014

Cell Death Dis

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Cellular events responsible for the initiation of major neurodegenerative disorders of the eye leading to blindness, including age-related macular degeneration, Stargardt and Best diseases, are poorly understood. Accumulation of vitamin A dimers, such as N-retinylidene-N-retinylethanolamine (A2E) in the retinal pigment epithelium (RPE), is one of the earliest measurable events preceding retinal degeneration. However, the extent to which these dimers contribute to tissue degeneration is not clear. To determine if A2E could trigger morphological changes associated with the degenerating RPE and subsequent cell death, we evaluated its toxicity to cultured human RPE cells (ARPE-19). We show that A2E triggered the accumulation of debris followed by a protracted death. A2E was up to≈14-fold more toxic than its precursor, retinaldehyde. Measurements reveal that the concentration of A2E in the aged human eye could exceed the concentration of all other retinoids, opening the possibility of A2E-triggered cell death by several reported mechanisms. Findings suggest that accumulation of vitamin A dimers such as A2E in the human eye might be responsible for the formation of ubiquitous RPE debris, an early indication of retinal degeneration, and that preventing or reducing the accumulation of vitamin A dimers is a prudent strategy to prevent blindness.

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“…Retinaldehyde 44 and A2E 45 have been shown, in culture, to induce greater cell death upon light exposure. We did not investigate the contribution of light.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells

Mihai

Washington

2014

Cell Death Dis

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“…Recently developed to minimize photothermal damage to the retina and adjacent structures, micropulse laser induces photochemical injury. 52 – 56 In this study, we investigated the migration and microglial nature of BM-derived cells present in the neurosensory retina (NSR) and RPE-choroid at various time points after subthreshold retinal phototherapy (SRPT) using various duty cycles (DCs).…”

mentioning

confidence: 99%

Bone Marrow–Derived Cell Recruitment to the Neurosensory Retina and Retinal Pigment Epithelial Cell Layer Following Subthreshold Retinal Phototherapy

Caballero

Kent²,

Sengupta

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeWe investigated whether subthreshold retinal phototherapy (SRPT) was associated with recruitment of bone marrow (BM)–derived cells to the neurosensory retina (NSR) and RPE layer.MethodsGFP chimeric mice and wild-type (WT) mice were subjected to SRPT using a slit-lamp infrared laser. Duty cycles of 5%, 10%, 15%, and 20% (0.1 seconds, 250 mW, spot size 50 μm) with 30 applications were placed 50 to 100 μm from the optic disc. In adoptive transfer studies, GFP+ cells were given intravenously immediately after WT mice received SRPT. Immunohistochemistry was done for ionized calcium-binding adapter molecule-1 (IBA-1+), CD45, Griffonia simplicifolia lectin isolectin B4, GFP or cytokeratin). Expression of Ccl2, Il1b, Il6, Hspa1a, Hsp90aa1, Cryab, Hif1a, Cxcl12, and Cxcr4 mRNA and flow cytometry of the NSR and RPE-choroid were performed.ResultsWithin 12 to 24 hours of SRPT, monocytes were detected in the NSR and RPE-choroid. Detection of reparative progenitors in the RPE occurred at 2 weeks using flow cytometry. Recruitment of GFP+ cells to the RPE layer occurred in a duty cycle–dependent manner in chimeric mice and in mice undergoing adoptive transfer. Hspa1a, Hsp90aa1, and Cryab mRNAs increased in the NSR at 2 hours post laser; Hif1a, Cxcl12, Hspa1a increased at 4 hours in the RPE-choroid; and Ccl2, Il1b, Ifng, and Il6 increased at 12 to 24 hours in the RPE-choroid.ConclusionsSRPT induces monocyte recruitment to the RPE followed by hematopoietic progenitor cell homing at 2 weeks. Recruitment occurs in a duty cycle–dependent manner and potentially could contribute to the therapeutic efficacy of SRPT.

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“…However, this retinoid still shows substantial absorption at > 410 nm wavelengths 165 . UV-A (355 nm) and blue (422 nm) light excitation of all-trans-retinal in the presence of oxygen generates singlet oxygen, which can in turn oxidize all-transretinal 166 . The degradation products, including several endoperoxides, shorter-chain aldehydes and epoxides, significantly increase all-trans-retinal cytotoxic effects on RPE cells in vitro 166 .…”

Section: Photoxicity Of All-trans-retinalmentioning

confidence: 99%

Photo-damage, photo-protection and age-related macular degeneration

Marquioni-Ramella

Suburo

2015

Photochem Photobiol Sci

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Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.

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Cytotoxicity of All‐Trans‐Retinal Increases Upon Photodegradation^†

Cited by 33 publications

References 45 publications

Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells

Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells

Bone Marrow–Derived Cell Recruitment to the Neurosensory Retina and Retinal Pigment Epithelial Cell Layer Following Subthreshold Retinal Phototherapy

Photo-damage, photo-protection and age-related macular degeneration

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Cytotoxicity of All‐Trans‐Retinal Increases Upon Photodegradation†

Cited by 33 publications

References 45 publications

Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells

Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells

Bone Marrow–Derived Cell Recruitment to the Neurosensory Retina and Retinal Pigment Epithelial Cell Layer Following Subthreshold Retinal Phototherapy

Photo-damage, photo-protection and age-related macular degeneration

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Cytotoxicity of All‐Trans‐Retinal Increases Upon Photodegradation^†