Photic Injury Research Articles

CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration.

Mononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie macrophage-driven retinal cell death. Monocytes were extracted from patients with AMD and differentiated into macrophages (hMdɸs), which were characterized based on proteomics, gene expression, and ex vivo and in vivo properties. Using bioinformatics, we identified the signaling pathway involved in macrophage-driven retinal cell death, and we assessed the therapeutic potential of targeting this pathway. We found that M2a hMdɸs were associated with retinal cell death in retinal explants and following adoptive transfer in a photic injury model. Moreover, M2a hMdɸs express several CCRI (C-C chemokine receptor type 1) ligands. Importantly, CCR1 was upregulated in Müller cells in models of retinal injury and aging, and CCR1 expression was correlated with retinal damage. Lastly, inhibiting CCR1 reduced photic-induced retinal damage, photoreceptor cell apoptosis, and retinal inflammation. These data suggest that hMdɸs, CCR1, and Müller cells work together to drive retinal and macular degeneration, suggesting that CCR1 may serve as a target for treating these sight-threatening conditions.

Identification of susceptibility loci for light-induced visual impairment in rats

Bright light exposure in animals results in the selective degeneration of the outer retina, known as “retinal photic injury” (RPI). The susceptibility to RPI differs among rat strains. WKY rats display susceptibility to RPI with extensive retinal degeneration observed in the sagittal eye specimen, whereas LEW strain rats are resistant to it, showing only slight or no degeneration. In the present study, we first established an ethological screening method using the Morris water maze to discern differential susceptibility among the living rats. WKY and LEW were crossed to produce the first filial generation (F1) offspring. Maze-trained individuals were exposed to bright, white light. The screening test results demonstrated that the susceptibility to light-induced visual impairment in rats is a dominant Mendelian susceptibility trait, as F1 rats were susceptible to visual impairment like WKY rats. Therefore, F1 rats were backcrossed with recessive LEW to produce the first backcross offspring (BC1). Subsequent recurrent backcrossing while selecting for the susceptibility, indicated a segregation ratio of ca. 24% in BC1 and BC2 generations, indicating the involvement of two or more genes in the susceptibility. Further, microsatellite analysis of BC1-to-BC4 individuals using microsatellite markers mapped two susceptibility loci on chromosome segments 5q36 and 19q11-q12, named RPI susceptibility (Rpi)1 and Rpi2, respectively. This study provides an insight into mechanisms underlying differential susceptibility, which could help decipher the mechanism underlying the onset/progression of human age-related macular degeneration.

Une maculopathie unilatérale chez un patient jeune : un phototraumatisme induit par laser

We report the case of a twenty-year-old man with a unilateral maculopathy responsible for an acute visual acuity loss and a sudden absolute central scotoma. His schizoid personality made the medical history fruitless. The patient's best corrected visual acuity was 20/60. Clinical examination revealed a strictly unilateral maculopathy with pigment remodeling and hyper-autofluorescent areas. Through this case report, we describe the characteristics of the lesion and the pathway to the diagnosis: a laser pointer-induced photic injury.

Nanocerium oxide increases the survival of adult rod and cone photoreceptor in culture by abrogating hydrogen peroxide-induced oxidative stress.

In vitro cell culture system for adult rod and cone photoreceptor (PR) is an effective and economical model for screening drug candidates against all kinds of age related retinal blindness. Interestingly, adult PR cells have a limited survival in the culture system, thus preventing full exploitation of this in vitro approach for drug screening applications. The limited survival of the adult PR cells in culture is due to their inherently high oxidative stress and photic injury. Mixed valence-state ceria nanoparticles have the ability to scavenge free radicals and reduce oxidative stress. Here, ceria nanoparticles of 5-10 nm dimensions have been synthesized, possessing dual oxidation state (+3 and +4) as evident from x-ray photoelectron spectroscopy and exhibiting real time reduction of hydrogen peroxide (H2O2) as quantified by absorbance spectroscopy and cyclic voltammogram analysis. Using flow cytometry and cell culture assay, it has been shown that, upon one time addition of 10 nM of nanoceria in the PR culture of the 18 months old adult common carp (Cyprinus carpio) at the time of plating the cells, the oxidative stress caused due to hydrogen peroxide assault could be abrogated. A further single application of nanoceria significantly increases the survival of these fragile cells in the culture, thus paving way for developing a more robust photoreceptor culture model to study the aging photoreceptor cells in a defined condition.

Photic injury to cultured RPE varies among individual cells in proportion to their endogenous lipofuscin content as modulated by their melanosome content.

We determined whether photic stress differentially impairs organelle motility of RPE lipofuscin and melanin granules, whether lethal photic stress kills cells in proportion to lipofuscin abundance, and whether killing is modulated by melanosome content. Motility of endogenous lipofuscin and melanosome granules within the same human RPE cells in primary culture was quantified by real-time imaging during sublethal blue light irradiation. Cell death during lethal irradiation was quantified by dynamic imaging of the onset of nuclear propidium iodide fluorescence. Analyzed were individual cells containing different amounts of autofluorescent lipofuscin, or similar amounts of lipofuscin and a varying content of phagocytized porcine melanosomes, or phagocytized black latex beads (control for light absorbance). Lipofuscin granules and melanosomes showed motility slowing with mild irradiation, but slowing was greater for lipofuscin. On lethal irradiation, cell death was earlier in cells with higher lipofuscin content, but delayed by the copresence of melanosomes. Delayed death did not occur with black beads, suggesting that melanosome protection was due to properties of the biological granule, not simple screening. Greater organelle motility slowing of the more photoreactive lipofuscin granule compared to melanosomes suggests that lipofuscin mediates mild photic injury within RPE cells. With lethal light stress endogenous lipofuscin mediates killing, but the effect is cell autonomous and modulated by coincident melanosome content. Developing methods to quantify the frequency of individual cells with combined high lipofuscin and low melanosome content may have value for predicting the photic stress susceptibility of the RPE monolayer in situ.

Is the mechanism of ‘poppers maculopathy’ photic injury?

'Poppers' is a slang term referring to recreational substances of abuse belonging to the alkyl nitrite family of compounds. Inhalation of the fumes from these volatile nitric oxide (NO) donors may provide a brief sense of euphoria and sexual arousal. Language: en

Photic Injury of the Eye(Psychological / Physiological Effect and Evaluation of Blue Light)

Photic Injury of the Eye(<Special Issue>Psychological / Physiological Effect and Evaluation of Blue Light)

Electrical stimulation ameliorates light-induced photoreceptor degeneration in vitro via suppressing the proinflammatory effect of microglia and enhancing the neurotrophic potential of Müller cells

Many types of electrical stimulation (ES) devices have been shown to promote the survival of degenerated neural cells, such as dopaminergic neurons in the medial forebrain bundle-transected rats, ischemic-injured cortical neurons and inner-and outer-nuclear-layer cells in degenerated retina. Using a rat photic injury model, our lab previously proved the neuroprotective effect of transcorneal electrical stimulation (TCES) on apoptotic photoreceptor cells. To delineate the mechanisms that might underlie this process, the effects of ES on light-damaged photoreceptor degeneration-induced microglia and Müller cell activation were investigated in the present in vitro study. Our data showed that ES (3ms, 20Hz, 300–1600μA) increased survival among light-reared cone-derived cells (661W) cultured alongside microglia or Müller cells analyzed by LDH and TUNEL assays. The degree of rescue was found to depend on the different intensities of the ES current. The immunocytochemistry revealed that ES significantly decreased the numbers of activated microglia cells with ameboid shapes and increased the numbers of reactive gliotic Müller cells with larger soma when they were co-cultured with light-damaged 661W cells. Real-time RT-PCR and Western blotting indicated that ES which was applied to different co-cultures and 661W cell-conditioned media (661WCM)-treated glia cultures had a prominent inhibitive effect on the secretion of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in microglia and a positive regulative effect on the production of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in Müller cells. The death rate of light-exposed 661W cells cultured with microglia was decreased significantly by the addition of neutralizing antibodies against IL-1β and TNF-α. On the other hand, the death rate of light-exposed 661W cells cultured with Müller cells was prominently increased when the co-culture was incubated in the presence of neutralizing antibody against BDNF while anti-CNTF neutralizing antibody did not induce additional exacerbation of the cell death among those 661W cells. These findings indicate the feasibility of using ES to create a nurturing environment for light-damaged photoreceptor cells. This environment is characterized by diminished microglial activation and fortified Müller cells reactive gliosis, which may have great potential in ameliorating photoreceptor damage. In this way, ES was here determined to be a novel, potent therapeutic option for delaying the progression of photoreceptor degeneration in patients suffering from retinitis pigmentosa (RP).

Shedding light on nanomedicine.

Light is an electromagnetic radiation that can convert its energy into different forms (e.g., heat, chemical energy, and acoustic waves). This property has been exploited in phototherapy (e.g., photothermal therapy and photodynamic therapy (PDT)) and optical imaging (e.g., fluorescence imaging) for therapeutic and diagnostic purposes. Light-controlled therapies can provide minimally- or noninvasive spatiotemporal control as well as deep tissue penetration. Nanotechnology provides numerous advantages, including selective targeting of tissues, prolongation of therapeutic effect, protection of active payloads, and improved therapeutic indices. This review explores the advances that nanotechnology can bring to light-based therapies and diagnostics, and vice versa, including photo-triggered systems, nanoparticles containing photoactive molecules, and nanoparticles that are themselves photoactive. Limitations of light-based therapies such as photic injury and phototoxicity are discussed.

Redox Proteomic Identification of Visual Arrestin Dimerization in Photoreceptor Degeneration after Photic Injury

Light-induced oxidative stress is an important risk factor for age-related macular degeneration, but the downstream mediators of photoreceptor and retinal pigment epithelium cell death after photic injury are unknown. Given our previous identification of sulfhydryl/disulfide redox status as a factor in photoreceptor survival, we hypothesized that formation of one or more disulfide-linked homo- or hetero-dimeric proteins might signal photoreceptor death after light-induced injury. Two-dimensional (non-reducing/reducing) gel electrophoresis of Wistar rat retinal homogenates after 10 hours of 10,000 lux (4200°K) light in vivo, followed by mass spectrometry identification of differentially oxidized proteins. The redox proteomic screen identified homodimers of visual arrestin (Arr1; S antigen) after toxic levels of light injury. Immunoblot analysis revealed a light duration-dependent formation of Arr1 homodimers, as well as other Arr1 oligomers. Immunoprecipitation studies revealed that the dimerization of Arr1 due to photic injury was distinct from association with its physiological binding partners, rhodopsin and enolase1. Systemic delivery of tris(2-carboxyethyl)phosphine, a specific disulfide reductant, both decreased Arr1 dimer formation and protected photoreceptors from light-induced degeneration in vivo. These findings suggest a novel arrestin-associated pathway by which oxidative stress could result in cell death, and identify disulfide-dependent dimerization as a potential therapeutic target in retinal degeneration.

Investigation on the protection of Tan-shen on RPE cells of rabbits against photic injury by SCGE.

Objective SCGE detect the protection of Tan-shen on RPE cells of rabbits against photic injury.Method The 2 ～4 passage RPE cells of rabbits were adopted to establish visible light damage model,The cultured RPE cells were pretreated with taurine of 0.2 mg/ml、0.8 mg/ml Tan-shen for 24hours,whereas control group was pretreated without Tan-shen.The cells DNA damage of various groups were detected with single cell gel electrophoresis assay.Results The DNA damage on RPE cells of rabbits was reduced,0.8mg/ml group have an advantage on other groups.There was great significant differece with control group in tail DNA percentage and tail length(P ＜0.01).Conclusion:Tan-shen can protect RPE cells of rabbits against photic injury.The effect was does-dependent. Key words: Tan-shen; RPE cells; Photic injury; SCGE

Update on physiopathology of cystoid macular edema

Abstract Purpose To offer an overview on the historical and most recent acquisitions about the mechanisms that have been proposed to explain how cystoid macular edema (CME) develops. Methods Review of the literature and presentation of personal evidences and imagines. Results CME represents an excessive presence of fluid within the layers of the retina. A breakdown in the blood‐retinal barrier normally is the causative event for fluid to accumulate in cystoid spaces within the retina. Several mechanisms have been proposed to explain the blood‐retinal barrier alteration and consequent CME formation. The intraocular diffusion of inflammatory mediators (eg, prostaglandins), following mechanical or biological insults, remains the most proven evidence. Another mechanism refers to the role of tractional forces on the macula from disruption of the normal vitreoretinal interface. According to this theory, a release of mediators that lead to a breakdown of the blood‐retinal barrier, would have triggered mainly by local forces. Photic injury, finally, has been implicated in the development of pseudophakic or post‐vitrectomy CME. Conclusion A full comprehension of the pathogenesis of CME will significantly help in focussing and developing an effective treatment even for the chronic form of CME.

AO imaging of acute macular diseases

Abstract Purpose To show clinical cases of acute macular diseases and their follow‐up by adaptive optics flood imaging. Methods Cases of acute retinal ischemia, of acute macular neuroretinopathy, of photic injury and of poppers‐related retinopathy have been observed by a prototypic adaptive optics flood imaging (ImagineEye corporation). Images from follow‐up examinations have been registered in order to obtain retinal monitoring at the single photoreceptor level. Iamges were compared to high resolution OCT scans. Results Precise extension and progression/regression of lesions could be documented in all cases. Acute macular neuroretinopathy showed residual cones persisting within an area devoid of any detectable cone. Minute progression and regression of lesions could be documented. Acute ischemia of the inner retina due to central retinal vein occlusion resulted in focal masking of the cone mosaic. The cone mosaic reappeared during follow‐up. Photic injury showed no changes over a 1 year follow‐up. Images of poppers‐related retinopathy showed partial improvement over time. Conclusion Adaptive optics flood imaging allows documentation of the extension and progression of acute maculopathies of various origins.

Müller cells upregulate the expression of SAP97 in light-injured rat retina

SAP97 is thought to play key roles in synapse assembly and synaptic plasticity. This study was carried out to determine whether it is involved in the Müller cell response to blue light injury. In light-injured rats, obvious intracellular edema in the outer retina was observed by transmission electron microscopy. The immunostaining of SAP97 was upregulated and concentrated in the Müller cell processes after photic injury, which was similar to the changes of AQP4 and the inwardly rectifying potassium channel, Kir4.1. Western blots showed that SAP97 and AQP4 protein levels were both increased on the third day after light exposure when compared with the control group (P<0.05). The upregulation of SAP97 coincides with the redistribution of AQP4 and Kir4.1 in blue light-injured rat retina.

Dendritic cells are early responders to retinal injury

The presence and activity of dendritic cells (DC) in retina is controversial, as these cells are difficult to identify in retina due to limited markers and sparse numbers. Transgenic mice that express green fluorescent protein (GFP) on the CD11c promoter to label DC allowed the visualization and quantification of retinal DC. Two retina injury models, the optic nerve crush (ONC) and light injury, were used to study their injury response. Many GFP + DC were tightly associated with retinal ganglion cell nerve fibers following ONC, while very few microglia (GFP −CD11b + cells) were found in close contact. The GFP + cells were greatly elevated in the outer plexiform layer following photic injury. All of the GFP + DC were CD11b +, suggesting a myeloid origin. In addition, the GFP + DC upregulated expression of MHC class II after injury, while the GFP −CD11b + microglia did not. This study shows that DC were found in the retina and that they rapidly responded to neural injuries. We propose that they are a previously overlooked population, distinct from microglia, and may be important in the injury response.

Discrete localization of various fatty-acid-binding proteins in various cell populations of mouse retina

Various fatty acids (FAs) are involved as an energy source in many different functions in the organism. They are also essential ingredients of membranous lipids and act as intracellular signaling molecules. Intracellular fatty-acid-binding proteins (FABPs) comprise a family of soluble lipid-binding proteins with low molecular masses and solubilize long-chain FAs to allow intracellular translocation in the aqueous cytosol. To clarify the functions of FABPs in the retina, which is remarkably rich in polyunsaturated FAs, we have investigated the localization of B (brain type)-, H (heart type)-, E (epidermal type)-, and A (adipocyte type)-FABPs in adult mouse retinae by immunohistochemistry. In order to determine the possible involvement of FABPs in retinal degenerative diseases, we have also examined changes in FABP expression in light-induced photoreceptor cell degeneration (photic injury). The discrete localization of B-, H-, E-, and A-FABP species in various cell populations of the retina has been clarified: B-FABP is mainly localized in the cone photoreceptor cells, H-FABP in some populations of amacrine/bipolar/horizontal interneurons, and E-FABP in ganglion cells, with A-FABP-like immunoreactivity being located in resident microglia of normal retinae. E-FABP has further been localized in invasive macrophages in damaged retinae following photic injury, allowing discrete identification of the resident microglia and invasive macrophages by A- and E-FABP immunoreactivity, respectively.

Photoreceptor Protection against Light Damage by AAV-Mediated Overexpression of Heme Oxygenase-1

To investigate whether overexpression of the cytoprotective gene heme oxygenase-1 (HO-1) in photoreceptors by gene delivery attenuates cellular injury caused by intense light damage and to document the possible mechanisms of protection. Recombinant adeno-associated virus type 5 (rAAV5) expressing the mouse HO-1 gene (mHO-1) was delivered to cyclic-light reared Sprague-Dawley (SD) rats by subretinal injection. Three weeks after transfer of HO-1 gene, animals were subjected to 2-hour intense light exposure then were returned to darkness. Expression of HO-1, p53, p38, and cellular FLICE inhibitory protein (c-FLIP) at different times after intense light damage was evaluated by Western blot analysis. HO-1 transgene expression, along with expression of c-fos and bcl-2, was analyzed by immunohistochemistry. In addition, the protective effects of HO-1 were evaluated by determining the morphology of the retina. Finally, apoptosis in photoreceptors was measured using TdT-dUTP terminal nick-end labeling (TUNEL) 24 hours after photic injury. Exogenous administration of HO-1 by gene transfer led to HO-1 transgene expression in photoreceptors. Protection of retina by HO-1 overexpression is evident from the partially preserved retina structure and attenuated apoptosis in photoreceptors after photic injury. Concurrently, overexpression of HO-1 was associated with a decrease in the expression of c-fos and p53, an increase in the activation of p38 and bcl-2, and preserved the expression of c-FLIP. Overexpression of HO-1 in photoreceptors protected themselves from subsequent cellular damage caused by intense light exposure. The anti-apoptotic mechanisms of HO-1 may be related to the induction of p38, bcl-2, and c-FLIP and to the suppression of c-fos and p53.

Morphologic study on protection of Acrysof IOL to acute retinal photic injury

目的 观察AcrySof Natural人工晶状体(IOL)对视网膜的保护作用.方法 以蓝光照射猪眼杯后极部视网膜,光照强度为20 J/cm2及40 J/cm2,设空白对照.照射方式:单独光照、透过AcrySof一片式IOL、透过AcrySof Natural IOL,照射后培养眼杯48 h,光镜和透射电镜观察.结果 相同光照强度下,单独光照组及AcrySof一片式IOL组视网膜各层损伤比无光照组及AcrySof Natural IOL组明显,而透过AcrySof Natural IOL照射组与无光照组相比,视网膜仍有部分损伤,但损伤明显较单独光照组及AcrySof一片式IOL组轻.照射方式相同时,40 J/cm2组比20 J/cm2组损伤明显.结论 20 J/cm2与40 J/cm2光照强度的蓝光均可造成新鲜离体猪视网膜的急性光损伤,且随能量增加,损伤加重.AcrySof一片式IOL与单独光照相比,视网光损伤程度相似.AcrySof Natural IOL与AcrySof一片式IOL相比,可减弱蓝光造成的视网膜急性光损伤。

Photic injury promotes cleavage of p75NTR by TACE and nuclear trafficking of the p75 intracellular domain

The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily that paradoxically mediates neuronal survival and differentiation or apoptotic cell death. Cleavage of p75NTR by a constitutively active metalloprotease could result in shedding of its extracellular domain (p75ECD) and generation of a pro-apoptotic intracellular domain (p75ICD). In this study, we established that exposure of a transgenic mouse photoreceptor cell line to intense light upregulated the expression of p75NTR and of the disintegrin metalloprotease tumor necrosis factor-converting enzyme (TACE) and resulted in apoptotic cell death. Light damage promoted TACE cleavage of p75NTR resulting in shedding of the soluble p75ECD and nuclear translocation of the p75ICD. Overexpression of TACE and p75NTR-induced p75NTR cleavage and secretion of p75ECD, but not nuclear transport of p75ICD. Light-induced cleavage of p75NTR, nuclear localization of p75ICD, and apoptosis were inhibited by IC-3, a metalloprotease inhibitor. Increased levels of p75NTR and TACE were observed in photoreceptor cells of animals with photic injury. Our findings support a role for TACE in the proteolytic cleavage of p75NTR and light-induced apoptosis.

Establishment and study of model of retinal photic injury in rabbit

目的 建立和研究视网膜光损伤动物模型,观察手术显微镜致兔眼视网膜光损伤的病理变化. 方法 将健康灰兔8只随机分为对照组、光损伤组,每组4只.所有实验动物均在循环光环境适应7 d,光照前暗适应24 h.实验前,散大瞳孔至8 mm左右.光损伤组光照(14 500 lux)30 min,暗适应30 min.光照48 h后取材制成超薄切片,电镜观察.对照组散瞳后不予光照,相应时间取材观察.结果对照组视网膜组织结构清楚,细胞形态规整.光损伤组光感受器外节膜盘崩解非常明显,外核层细胞排列紊乱,核固缩.色素上皮层核染色质边集,呈现细胞凋亡的早期改变,线粒体空泡变性.结论手术显微镜(14 500lux)可诱导兔视网膜光损伤,病理特点是光感受器的退行性改变。