Action spectrum for photochemical retinal pigment epithelium (RPE) disruption in an in vivo monkey model

Zhang, Jie; Sabarinathan, R.; Bubel, Tracy; Williams, David R.; Hunter, Jennifer J.

doi:10.1117/12.2213615

Cited by 5 publications

(8 citation statements)

References 9 publications

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“…Based on previous reports it can be expected that the radiant exposure of 369 J/cm 2 needed for development of oxidized DHA-like fluorescence could be photoxic to cells especially if they contain lipofuscin [24][25][26]48,[69][70][71][72][73][74]. Friedman and Kuwabara observed severe retinal damage in the photoreceptors and changes to the retinal pigment epithelium in rhesus monkeys who were exposed for 15 min to light from an indirect ophthalmoscope providing a retinal irradiance of 270 mW/cm 2 and a dose of 243 J/cm 2 [70].…”

Section: Exposure Of Lipofuscin-laden Arpe-19 Cells To Light Results In Loss Of Lipofuscin From Cells and Spectral Changes Of Fluorescencmentioning

confidence: 99%

“…The threshold dose to cause a visible RPE photodamage in macaque monkey by 568 nm laser has been determined as 247 J/cm 2 . Radiant exposures sufficient to cause photodamage to the retina were even smaller when shorter irradiation wavelengths were used [26,72]. Using photoexcitation of macaque retina in vivo with 488 nm light, a photobleaching of fluorescence with some disruption of the RPE monolayer was observed after radiant exposure of just 79 J/cm 2 and even smaller than that for exposure with 460 nm light [26,72].…”

Section: Exposure Of Lipofuscin-laden Arpe-19 Cells To Light Results In Loss Of Lipofuscin From Cells and Spectral Changes Of Fluorescencmentioning

confidence: 99%

“…Radiant exposures sufficient to cause photodamage to the retina were even smaller when shorter irradiation wavelengths were used [26,72]. Using photoexcitation of macaque retina in vivo with 488 nm light, a photobleaching of fluorescence with some disruption of the RPE monolayer was observed after radiant exposure of just 79 J/cm 2 and even smaller than that for exposure with 460 nm light [26,72]. Cultured RPE cells are also susceptible to photodamage and it has been shown that internalized lipofuscin makes them even more susceptible to phototoxicic effects of light in comparison to cells without lipofuscin [48, 59,71,[73][74][75].…”

Section: Exposure Of Lipofuscin-laden Arpe-19 Cells To Light Results In Loss Of Lipofuscin From Cells and Spectral Changes Of Fluorescencmentioning

confidence: 99%

“…The shorter excitation wavelength can also impose an increased risk of phototoxicity (reviewed in [66]). Following discovery that the phototoxicity thresholds of radiant exposures used for light safety standards were incorrect for 568 nm light [24][25][26], Zhang and colleagues determined the phototoxicity thresholds for several other wavelengths which include 460 nm light [72]. Further experiments are needed to determine whether using excitation of lipofuscin and retina with light of 460 nm wavelength, or shorter, can produce useful information about the lipofuscin content and its oxidation state, and whether it is feasible to use this approach in clinical setting without risking retinal photodamage.…”

Section: Decrease In Long-wavelength Fluorescence During Photooxidation Of Lipofuscin and An Increase In Blue/cyan Or Green To Orange Flumentioning

confidence: 99%

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Photodegradation of Lipofuscin in Suspension and in ARPE-19 cells and the Similarity of Fluorescence of the Photodegradation Product with Oxidized Docosahexaenoate

Różanowska¹,

Rozanowski²

2021

Preprint

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Retinal lipofuscin accumulates with age in the retinal pigment epithelium (RPE) where its fluorescence properties are used to assess the retinal health. It was observed that there is a decrease in lipofuscin fluorescence above the age of 75 years and in early stages of age-related macular degeneration (AMD). The purpose of this study was to investigate the response of lipofuscin isolated from human RPE, and lipofuscin-laden-cells to visible light, and determine whether an abundant component of lipofuscin, docosahexaenoate (DHA) can contribute to lipofuscin fluorescence upon oxidation. Exposure of lipofuscin to visible leads to a decrease of its long-wavelength fluorescence at about 610 nm with concomitant growth of the short-wavelength fluorescence. The emission spectrum of photodegraded lipofuscin exhibits similarity with that of oxidized DHA. Exposure to light of lipofuscin-laden cells leads to loss of lipofuscin granules from cells, while retaining cell viability. The spectral changes of fluorescence in lipofuscin-laden cells resemble those seen during photodegradation of isolated lipofuscin. Our results demonstrate that fluorescence emission spectra together with quantitation of intensity of long-wavelength fluorescence can serve as a marker useful for lipofuscin quantification and for monitoring its oxidation, thereby useful for screening the retina for increased oxidative damage and early AMD-related changes.

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Section: Exposure Of Lipofuscin-laden Arpe-19 Cells To Light Results In Loss Of Lipofuscin From Cells and Spectral Changes Of Fluorescencmentioning

confidence: 99%

Section: Exposure Of Lipofuscin-laden Arpe-19 Cells To Light Results In Loss Of Lipofuscin From Cells and Spectral Changes Of Fluorescencmentioning

confidence: 99%

Section: Exposure Of Lipofuscin-laden Arpe-19 Cells To Light Results In Loss Of Lipofuscin From Cells and Spectral Changes Of Fluorescencmentioning

confidence: 99%

Section: Decrease In Long-wavelength Fluorescence During Photooxidation Of Lipofuscin and An Increase In Blue/cyan Or Green To Orange Flumentioning

confidence: 99%

See 2 more Smart Citations

Photodegradation of Lipofuscin in Suspension and in ARPE-19 cells and the Similarity of Fluorescence of the Photodegradation Product with Oxidized Docosahexaenoate

Różanowska¹,

Rozanowski²

2021

Preprint

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“…Lipofuscin fluorescence was excited with a 561 nm laser at 35 µW and imaged with an emission filter centered at 624 nm (Δ40 nm). This instrument has been described previously [45][46][47][48]. …”

Section: Auxiliary Imagingmentioning

confidence: 99%

Safety assessment in macaques of light exposures for functional two-photon ophthalmoscopy in humans

Schwarz¹,

Sharma²,

Fischer³

et al. 2016

Biomed. Opt. Express

Self Cite

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Two-photon ophthalmoscopy has potential for in vivo assessment of function of normal and diseased retina. However, light safety of the sub-100 fs laser typically used is a major concern and safety standards are not well established. To test the feasibility of safe in vivo two-photon excitation fluorescence (TPEF) imaging of photoreceptors in humans, we examined the effects of ultrashort pulsed light and the required light levels with a variety of clinical and high resolution imaging methods in macaques. The only measure that revealed a significant effect due to exposure to pulsed light within existing safety standards was infrared autofluorescence (IRAF) intensity. No other structural or functional alterations were detected by other imaging techniques for any of the exposures. Photoreceptors and retinal pigment epithelium appeared normal in adaptive optics images. No effect of repeated exposures on TPEF time course was detected, suggesting that visual cycle function was maintained. If IRAF reduction is hazardous, it is the only hurdle to applying two-photon retinal imaging in humans. To date, no harmful effects of IRAF reduction have been detected.

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Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

Różanowska¹

2023

Preprint

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Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

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Action spectrum for photochemical retinal pigment epithelium (RPE) disruption in an in vivo monkey model

Cited by 5 publications

References 9 publications

Photodegradation of Lipofuscin in Suspension and in ARPE-19 cells and the Similarity of Fluorescence of the Photodegradation Product with Oxidized Docosahexaenoate

Photodegradation of Lipofuscin in Suspension and in ARPE-19 cells and the Similarity of Fluorescence of the Photodegradation Product with Oxidized Docosahexaenoate

Safety assessment in macaques of light exposures for functional two-photon ophthalmoscopy in humans

Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina

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