Light-induced Apoptosis: Differential Timing in the Retina and Pigment Epithelium

Hafezi, Farhad; Marti, Andreas; Munz, K.; Remé, Charlotte E.

doi:10.1006/exer.1997.0288

Cited by 115 publications

(74 citation statements)

References 34 publications

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“…The pyknosis of nuclei and DNA fragmentation usually begins 8-12 h after the 6 h period of light exposure at 2,700 lux intensity ( 15,16,56,57 ) also be important for photoreceptor cell death. Our results show prominent ceramide immunoreactivity in the RPE following light stress ( Fig.…”

Section: Light Stress Increases Ceramide Content In the Retinamentioning

confidence: 99%

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration

Chen

Tran

Eckerd

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org pigmentosa and age-related macular degeneration ( 1-3 ). Very few effective therapies exist for this heterogeneous group of diseases because of the complex pathophysiology associated with genetic and environmental factors. Researchers are looking for cellular second messengers involved in the process of cell death which can be targeted for therapies. The sphingolipid metabolite ceramide is a deadly second messenger in the cell and can induce apoptosis through various mechanisms ( 4 ). Recently, increases in ceramide levels have been shown to be associated with photoreceptor and retinal pigment epithelium (RPE) cell death ( 5-8 ). Here we investigated whether ceramide is involved in photoreceptor cell death in light-induced retinal degeneration (LIRD).LIRD is a useful model for studying the mechanism of photoreceptor cell death because intense light exposure induces oxidative stress-mediated apoptosis of photoreceptor cells and causes retinal degeneration ( 3, 9 ). Since its development in 1966 by Noell et al. ( 10 ), this model, in combination with genetic knock-out models (1)(2)(3)(11)(12)(13)(14), has been extensively used to discover many fundamental mechanisms of photoreceptor function and to test various neuroprotective compounds ( 15-21 ).However, the precise mechanism of light-induced retinal degeneration is currently unclear ( 3, 13 ). In past decades, accumulating evidence suggested that ceramide, the core lipid of sphingolipid metabolism, is a key factor in apoptotic cell death ( 4,(22)(23)(24)(25). Various external stressors, such as hypoxia, chemotherapeutic agents, heat, ultravioAbstract Light-induced retinal degeneration (LIRD) in albino rats causes apoptotic photoreceptor cell death. Ceramide is a second messenger for apoptosis. We tested whether increases in ceramide mediate photoreceptor apoptosis in LIRD and if inhibition of ceramide synthesis protects the retina. Sprague-Dawley rats were exposed to 2,700 lux white light for 6 h, and the retinal levels of ceramide and its intermediary metabolites were measured by GC-MS or electrospray ionization tandem mass spectrometry. Enzymes of the de novo biosynthetic and sphingomyelinase pathways of ceramide generation were assayed, and gene expression was measured. The dosage and temporal effect of the ceramide synthase inhibitor FTY720 on the LIRD retina were measured by histological and functional analyses. Retinal ceramide levels increased coincident with the increase of dihydroceramide at various time points after light stress. Light stress in retina induces ceramide generation predominantly through the de novo pathway, which was prevented by systemic administration of FTY720 (10 mg/kg) leading to the protection of retinal structure and function. The neuroprotection of FTY720 was independent of its immunosuppressive action. We conclude that ceramide increase by de novo biosynthesis mediates photoreceptor apoptosis in the LIRD model and that inhibition of ceramide production protects the retina ag...

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Section: Light Stress Increases Ceramide Content In the Retinamentioning

confidence: 99%

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration

Chen

Tran

Eckerd

et al. 2013

Journal of Lipid Research

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“…At the same time, excessive illumination of photoreceptor cells can induce their apoptosis, which in turn leads to degeneration of retina (31). Light activation of Rho is required for lightinduced retinal degeneration.…”

Section: Discussionmentioning

confidence: 99%

Visible Light Modulates the Expression of Cancer-Retina Antigens

Bazhin

Schadendorf

Owen

et al. 2008

Molecular Cancer Research

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Proteins involved in the visual signaling cascade show light-dependent expression levels in photoreceptor cells. Recently, these proteins have been described to be expressed in neuroectodermal tumors and to function as cancer-retina antigens. Here, we show that light can down-regulate gene expression of rhodopsin, transducin, and cyclic guanosine 3 ¶,5 ¶-monophosphate phosphodiesterase 6 (PDE6) and up-regulate guanylyl cyclase 1, recoverin, and arrestin in human melanoma cells in vitro, comparable to physiologic changes earlier observed in photoreceptor cells. Similar modulation can be detected at the protein level in melanoma cells except for no changes in PDE6 protein levels. Two regulatory pathways have been identified: Sp1/Sp3/Sp4 proteins for rhodopsin and PDE6, and mitogen-activated protein kinases for recoverin and arrestin. The visual cascade and retinoic acid as its derivate do not play any role in this process. Putative explanations for light-dependent modulation of cancer-retina antigen expression in melanoma cells are discussed.

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“…Secondly, the debate on the role of blue light exposure and AMD has continued for almost three decades, only a large-scale randomized clinical trial will have sufficient power to provide conclusive evidence. Thirdly, even a modest beneficial effect is likely to be associated with substantial individual and socio-economic benefits because AMD is reaching epidemic proportions, both here and in the UK (Evans and Wormald, 1996;Organisciak and Vaughan, 2010;Hafezi et al, 1997).…”

Section: Issue #4mentioning

confidence: 99%

Combatant Eye Protection: An Introduction to the Blue Light Hazard

Lattimore¹

2015

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The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing the burden, Introduction -Combat spectacles have successfully provided protection from penetrating ocular injury for over 5 years; the primary obstacle to their successful performance had been getting Soldiers to actually wear the protective gear. As success stories emerged (via photographic evidence), compliance rates approached 100%. The risk of functional eye injury resulting from visible solar radiation has been less obvious. Moreover, the risk of functional ocular tissue injury from LED-generated radiant energy remains under scrutiny. All LEDs (i.e., those embedded within digital tactical display systems, flat panel instrument displays, computer monitors, and televisions) can possess major energy outputs across the blue spectrum, independent of their apparent white or observational color. Methods -This report is based on current data-extrapolation from prior work that had quantified alterations in rabbit corneal metabolic activity secondary to in-vivo UV exposures. [nm], 300 nm, 310 nm, and 360 nm), the exposures varied from 0.05 J/cm 2 to 0.25 J/cm 2 (in 0.05 J/cm 2 steps), based on the need to maintain environmental relevance. Micro-polarographic corneal oxygen uptake rates served as the in-vivo index of alteration in oxidative metabolic rate. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) SPONSOR/MONITOR'S REPORT NUMBER(S)Results -A multi-factorial analysis of variance exhibited an overall significant between-groups effect by wavelength (p < 0.0001), as well as an interactive effect between wavelength and radiant energy dose (p < 0.005). Control eyes were stable. Extrapolation of the nonlinear trend lines out into visible wavelengths reached baseline near 447 nm.Discussion -Evidence of metabolic vulnerability to visible light extending well into the blue spectrum is vitally important, as this is indicative of a moving, scalable effect, with no traditional threshold delineating expectation of damage/no damage. Added stressors (e.g., increased altitude or contact lens wear) could shift the wavelength effects toward a more damaging clinical picture. Recent reports have indicated rod photo-pigment damage resulting from solar blue-light exposures, adversely affecting unaided night vision, a militarily important performance decrement.Conclusion -The incorporation of blue filters in conjunction with current protective eyewear represents one potentially proactive solution, but there are limits. A defined research program regarding establishment of human functional ocular parameter limits would be essential to overall safety. The activation wavelength for...

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Light-induced Apoptosis: Differential Timing in the Retina and Pigment Epithelium

Cited by 115 publications

References 34 publications

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration

Visible Light Modulates the Expression of Cancer-Retina Antigens

Combatant Eye Protection: An Introduction to the Blue Light Hazard

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