Retinal light damage: Mechanisms and protection

Organisciak, Daniel T.; Vaughan, Dana K.

doi:10.1016/j.preteyeres.2009.11.004

Cited by 477 publications

(420 citation statements)

References 244 publications

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“…Previous studies have described two types of damages induced by light: the first involves rhodopsin and affects photoreceptors 19, 39, 40. The second concerns the RPE which is selectively vulnerable to high‐energy blue light 41, 42.…”

Section: Discussionmentioning

confidence: 99%

Effects of white light‐emitting diode (LED) exposure on retinal pigment epithelium in vivo

Jaadane

Rodriguez

Boulenguez

et al. 2017

J Cellular Molecular Medi

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Ageing and alteration of the functions of the retinal pigment epithelium (RPE) are at the origin of lost of vision seen in age‐related macular degeneration (AMD). The RPE is known to be vulnerable to high‐energy blue light. The white light‐emitting diodes (LED) commercially available have relatively high content of blue light, a feature that suggest that they could be deleterious for this retinal cell layer. The aim of our study was to investigate the effects of “white LED” exposure on RPE. For this, commercially available white LEDs were used for exposure experiments on Wistar rats. Immunohistochemical stain on RPE flat mount, transmission electron microscopy and Western blot were used to exam the RPE. LED‐induced RPE damage was evaluated by studying oxidative stress, stress response pathways and cell death pathways as well as the integrity of the outer blood–retinal barrier (BRB). We show that white LED light caused structural alterations leading to the disruption of the outer blood–retinal barrier. We observed an increase in oxidized molecules, disturbance of basal autophagy and cell death by necrosis. We conclude that white LEDs induced strong damages in rat RPE characterized by the breakdown of the BRB and the induction of necrotic cell death.

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Section: Discussionmentioning

confidence: 99%

Effects of white light‐emitting diode (LED) exposure on retinal pigment epithelium in vivo

Jaadane

Rodriguez

Boulenguez

et al. 2017

J Cellular Molecular Medi

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“…We had hypothesized that if autophagy were a critical process for resisting light-induced damage that inhibiting this pathway in the light-stress-resistant C57BL/6J strain 41,42 would make them more susceptible to damage. This was not the case as we could not accelerate rod degeneration by intense light exposure of the Atg5 ΔRod mice.…”

Section: Discussionmentioning

confidence: 99%

“…41,42 Mice with a leucine at position 450 (Leu-450) (e.g., BALB/c and 129) are susceptible to light stress, whereas mice with a methionine at position 450 (Met-450) (e.g., C57BL/6) are resistant. The Leu-450 amino acid results in an accelerated RPE visual cycle and leads to degeneration of the photoreceptors because of the rapid accumulation of toxic visual cycle products in the RPE.…”

Section: Rod Degeneration In Atg5mentioning

confidence: 99%

Autophagy supports survival and phototransduction protein levels in rod photoreceptors

et al. 2015

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Damage and loss of the postmitotic photoreceptors is a leading cause of blindness in many diseases of the eye. Although the mechanisms of photoreceptor death have been extensively studied, few studies have addressed mechanisms that help sustain these non-replicating neurons for the life of an organism. Autophagy is an intracellular pathway where cytoplasmic constituents are delivered to the lysosomal pathway for degradation. It is not only a major pathway activated in response to cellular stress, but is also important for cytoplasmic turnover and to supply the structural and energy needs of cells. We examined the importance of autophagy in photoreceptors by deleting the essential autophagy gene Atg5 specifically in rods. Loss of autophagy led to progressive degeneration of rod photoreceptors beginning at 8 weeks of age such that by 44 weeks few rods remained. Cone photoreceptor numbers were only slightly diminished following rod degeneration but their function was significantly decreased. Rod cell death was apoptotic but was not dependent on daily light exposure or accelerated by intense light. Although the light-regulated translocation of the phototransduction proteins arrestin and transducin were unaffected in rods lacking autophagy, Atg5-deficient rods accumulated transducin-α as they degenerated suggesting autophagy might regulate the level of this protein.This was confirmed when the light-induced decrease in transducin was abolished in Atg5-deficient rods and the inhibition of autophagy in retinal explants cultures prevented its degradation. These results demonstrate that basal autophagy is essential to the long-term health of rod photoreceptors and a critical process for maintaining optimal levels of the phototransduction protein transducin-α. As the lack of autophagy is associated with retinal degeneration and altered phototransduction protein degradation in the absence of harmful gene products, this process may be a viable therapeutic target where rod cell loss is the primary pathologic event. Autophagy is an intracellular pathway where cytoplasmic constituents are delivered to the lysosomes for degradation. Defective autophagy can contribute to the age-dependent accumulation of damaged proteins and organelles leading to altered cellular homeostasis and loss of function. [1][2][3][4][5] The metabolic roles of autophagy can be classified into two types, basal and induced. In nutrient-rich conditions, autophagy is suppressed but still occurs at low levels (basal autophagy); however, when cells are subjected to stress (starvation, injury, hypoxia), autophagy is activated immediately (induced autophagy). 6 Induced autophagy maintains the amino acid pool inside cells to adapt to starvation while constitutive autophagy has been shown to function as a cell-repair mechanism that is important for long-lived postmitotic cells. 7-11 Defects in autophagy have been associated with neurodegenerative diseases, 12-15 diabetes, 16,17 lysosomal storage disease 18 and the loss of vision. 19 In addition to macroautophagy, m...

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“…One risk factor, oxidative stress, has been implicated as an important mechanism contributing to cell death in several neurodegenerative diseases, including photoreceptor loss in the dry form of AMD and nonsyndromic RP (2, 13, 49, 50). Oxidative stress may cause damage to proteins, nucleic acids, and lipids, rendering it a potentially important therapeutic target (1,3,15). As demonstrated here and elsewhere, light exposure can result in the generation of excessive ROS.…”

Section: Discussionmentioning

confidence: 53%

“…Understanding disease mechanisms and interactions of causative factors should help in the design of treatment strategies. Recent evidence indicates that oxidative stress, contributing to photoreceptor cell death, plays a significant role in the pathophysiology of nonsyndromic retinitis pigmentosa (RP) and possibly age-related macular degeneration (AMD) (1)(2)(3). Moreover, light-induced oxidative stress is known to potentiate photoreceptor loss in genetic models mimicking a number of human retinal degenerations (4)(5)(6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

MEF2D haploinsufficiency downregulates the NRF2 pathway and renders photoreceptors susceptible to light-induced oxidative stress

Nagar

Noveral

Trudler

et al. 2017

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

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Gaining mechanistic insight into interaction between causative factors of complex multifactorial diseases involving photoreceptor damage might aid in devising effective therapies. Oxidative stress is one of the potential unifying mechanisms for interplay between genetic and environmental factors that contribute to photoreceptor pathology. Interestingly, the transcription factor myocyte enhancer factor 2d (MEF2D) is known to be important in photoreceptor survival, as knockout of this transcription factor results in loss of photoreceptors in mice. Here, using a mild light-induced retinal degeneration model, we show that the diminished MEF2D transcriptional activity in Mef2d +/− retina is further reduced under photostimulation-induced oxidative stress. Reactive oxygen species cause an aberrant redox modification on MEF2D, consequently inhibiting transcription of its downstream target, nuclear factor (erythroid-derived 2)-like 2 (NRF2). NRF2 is a master regulator of phase II antiinflammatory and antioxidant gene expression. In the Mef2d heterozygous mouse retina, NRF2 is not up-regulated to a normal degree in the face of lightinduced oxidative stress, contributing to accelerated photoreceptor cell death. Furthermore, to combat this injury, we found that activation of the endogenous NRF2 pathway using proelectrophilic drugs rescues photoreceptors from photo-induced oxidative stress and may therefore represent a viable treatment for oxidative stress-induced photoreceptor degeneration, which is thought to contribute to some forms of retinitis pigmentosa and age-related macular degeneration.B lindness due to photoreceptor loss from a number of diseases is a prevalent and devastating condition in the human population. Genetic predisposition and environmental stress play major roles in the incidence and progression of the retinal degeneration. Understanding disease mechanisms and interactions of causative factors should help in the design of treatment strategies. Recent evidence indicates that oxidative stress, contributing to photoreceptor cell death, plays a significant role in the pathophysiology of nonsyndromic retinitis pigmentosa (RP) and possibly age-related macular degeneration (AMD) (1-3). Moreover, light-induced oxidative stress is known to potentiate photoreceptor loss in genetic models mimicking a number of human retinal degenerations (4-11).The oxidizing microenvironment of the retinal pigment epithelium (RPE)-photoreceptor complex has been predominantly attributed to high oxygen demand, abundant polyunsaturated fatty acids, and direct exposure to light, coupled with the adjacent choroidal hemodynamics (12). Light exposure compounded over many years in the presence of photosensitizers may prime photoreceptors and RPE for free radical/oxidative damage (12-14). In some animal models of photoreceptor degeneration, including RP and Leber congenital amaurosis, disease progression is accelerated by exposure to light and slowed by rearing in darkness (3, 15). Advanced age also compromises the endogenous antioxidant ...

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Retinal light damage: Mechanisms and protection

Cited by 477 publications

References 244 publications

Effects of white light‐emitting diode (LED) exposure on retinal pigment epithelium in vivo

Effects of white light‐emitting diode (LED) exposure on retinal pigment epithelium in vivo

Autophagy supports survival and phototransduction protein levels in rod photoreceptors

MEF2D haploinsufficiency downregulates the NRF2 pathway and renders photoreceptors susceptible to light-induced oxidative stress

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