Retinal protective effect of curcumin metabolite hexahydrocurcumin against blue light-induced RPE damage.

BACKGROUND: Age-related macular degeneration (AMD) is a disease of retinal pigment epithelium (RPE) cells. We have previously demonstrated that blue light can damage RPE cells and their underlying mechanisms. We found that hexahydrocurcumin (HHC), a metabolite of curcumin, had better retinal protection than curcumin. However, the involved mechanisms remain unclear. METHODS: By exposing ARPE-19 human RPE cells and mouse primary RPE cells to blue light, the intracellular mechanisms of HHC in cells were investigated, including the proliferation of RPE cells and the effects of HHC on activating intracellular protective mechanisms and related factors. Next-generation sequencing (NGS) RNA sequencing revealed the underlying mechanisms involved in the induction and regulation of HHC treatment following blue light exposure. RESULTS: HHC promoted autophagy by enhancing autophagic flux, reduced oxidative stress and endoplasmic reticulum (ER) stress, and effectively reversed blue light-induced cell death. RNA sequencing-based bioinformatics approaches comprehensively analyze HHC-mediated cellular processes. CONCLUSION: Our findings elucidate the mechanisms of HHC against blue light damage in RPE cells and are beneficial for the development of natural metabolite-based preventive drugs or functional foods.

The Role of Oxidative Stress and Autophagy in Blue-Light-Induced Damage to the Retinal Pigment Epithelium in Zebrafish In Vitro and In Vivo.

Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm2 for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24-48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light's effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.

Choroidal Neovascularization Secondary to Intense Pulsed Light Injury.

The authors report a 26-year-old medical device saleswoman developing choroidal neovascularization after injury by intense pulsed light with detection and monitoring by optical coherence tomography angiography and treatment with intravitreal injection of ranibizumab. This is the first intense pulsed light-related choroidal neovascularization case, which reminds the importance of using appropriate eye protection throughout the course of treatment for all individuals present in the therapy room.

Differential autophagic effects of vital dyes in retinal pigment epithelial ARPE-19 and photoreceptor 661W cells.

Indocyanine green (ICG) and brilliant blue G (BBG) are commonly used vital dyes to remove internal limiting membrane (ILM) in vitreoretinal surgery. The vital dyes have shown cytotoxic effects in ocular cells. Autophagy is a stress responsive pathway for either protecting cells or promoting cell death. However, the role of autophagy in ocular cells in response to the vital dyes remains unknown. In this study, we found that ICG and BBG reduced cell viability in both human retinal pigment epithelial ARPE-19 and mouse photoreceptor 661W cells. ICG and BBG induced lipidated GFP-LC3-II and LC3-II in ARPE-19 and 661W cells. Combination treatment with the autophagy inhibitor chloroquine indicated that ICG and BBG reduced autophagic flux in ARPE-19 cells, whereas the vital dyes induced autophagic flux in 661W cells. Moreover, genetic and pharmacological ablation of autophagy enhanced vital dyes-induced cytotoxicity in ocular cells. Dietary supplements, including resveratrol, lutein, and CoQ10, induced autophagy and diminished the cytotoxic effects of ICG and BBG in ocular cells. These results suggest that autophagy may protect ARPE-19 and 661W cells from vital dyes-induced damage.

Differential effects of bevacizumab, ranibizumab and aflibercept on cell viability, phagocytosis and mitochondrial bioenergetics of retinal pigment epithelial cell.

PURPOSE: To evaluate the short- and long-term effects of most clinically used anti-vascular endothelial growth factor agents, including bevacizumab, ranibizumab or aflibercept, on cell viability, phagocytosis, mitochondrial bioenergetics and the oxidant acrolein-induced oxidative stress of human adult retinal pigment epithelial (ARPE)-19 cells. METHODS: In cultured ARPE-19 cells, cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, phagocytotic activity and intracellular reactive oxygen species (ROS) level were determined by flow cytometry, mitochondrial bioenergetics was assessed using a Seahorse XF24 Extracellular Flux Analyzer, and protein expression was measured by Western blotting. RESULTS: Long-term exposure to all three agents had no effect on cell viability; but rescued the ARPE-19 cells from acrolein-induced decrease in cell viability. Bevacizumab, but not ranibizumab or aflibercept, suppressed the phagocytotic activity of ARPE-19 cells and exerted significantly less protection against acrolein-induced inhibition of phagocytosis. Both ranibizumab and aflibercept increased basal respiratory rate and maximal mitochondrial respiratory capacity after 1-hr exposure; but returned to baseline following 24- or 72-hr exposure. In contrast, both responses were reduced on short-term exposure, but augmented after long-term exposure to bevacizumab. Long-term pretreatment with all three agents reversed acrolein-induced impairment of mitochondrial bioenergetics, overproduction of ROS and phosphorylation of the mitogen-activated protein kinases in ARPE-19 cells. CONCLUSION: Bevacizumab might affect mitochondrial bioenergetics differently from that by ranibizumab and aflibercept. Ranibizumab and aflibercept at their therapeutic dose protect against acrolein-induced oxidative cytotoxicity in human ARPE-19 cells via an increase in mitochondrial bioenergetics. An early protective action on mitochondrial bioenergetic capacity might be used to predict possible long-term antioxidative effects of the agents in the eye.

Resveratrol stimulates mitochondrial bioenergetics to protect retinal pigment epithelial cells from oxidative damage.

PURPOSE: Resveratrol (RSV) alleviates oxidative damage in human adult retinal pigment epithelial (ARPE) cells. Mitochondrial bioenergetics is associated with oxidative stress. The purpose of this study was to examine the role of mitochondrial bioenergetics in the cytoprotective effect of RSV. Its role in protection against the adverse effects of cigarette smoke (CS) in experimental choroidal neovascularization (CNV) was also examined. METHODS: Cultured ARPE-19 cells were treated with acrolein alone or acrolein with added RSV. Temporal changes in cell viability, expression of the antioxidant protein, and mitochondrial bioenergetics were evaluated. In an animal study, CNV lesions were created in Brown Norway rats by laser-induced photocoagulation. Effects of CS alone or with additional RSV treatment on CNV lesions were quantified by fundus fluorescein angiography. RESULTS: In ARPE-19 cells, RSV rescued acrolein-induced cell death, alongside reversal of acrolein-induced superoxide dismutase expression. Resveratrol increased the mitochondrial bioenergetics, including basal respiratory rate, adenosine triphosphate synthesis via oxidative phosphorylation, and maximal mitochondrial capacity. In animal experiments, CS induced a significant increase in CNV following laser injury, and this increase in CNV was appreciably prevented following peripheral infusion of RSV. CONCLUSIONS: Our results indicate that RSV, a major polyphenol found in red wine, exerts protection against acrolein-induced cytotoxicity in human ARPE-19 cells via increases in the mitochondrial bioenergetics. In addition, the antioxidant effect of RSV may contribute to protection against laser-induced CNV in animals exposed to CS. Therefore, RSV might be beneficial for treatment of acrolein-induced or CS-evoked RPE degeneration.

Male sex as a risk factor for pseudophakic retinal detachment after cataract extraction in Taiwanese adults.

PURPOSE: To investigate the role of sex in modifying risk factors for retinal detachment (RD) after cataract surgery. DESIGN: Prospective cohort study based on medical records and insurance claims from Taiwan's Bureau of National Health Insurance (BNHI). PARTICIPANTS: Nine thousand three hundred eighty-eight patients who underwent extracapsular cataract extraction (CE), including phacoemulsification procedures, between August 1999 and December 2001. METHODS: Medical charts and claims submitted by insurance beneficiaries who underwent CE and intraocular lens implantation were collected from the sixth branch of the BNHI. Data recorded for analysis included each patient's demographic characteristics, medical history, refractive status, axial length (AL), type of CE, and intraoperative complications. Posterior capsulotomy, diagnostic procedures, and treatments for retinal complications and other ocular diseases were identified on the basis of codes from physicians' billing records at the end of 2005. MAIN OUTCOME MEASURES: Incidence of RD in the full study group and in subgroups defined by sex, age, AL, type of CE procedure, concurrent systemic diseases, presence of intraoperative complications, and subsequent posterior capsulotomy. RESULTS: The mean follow-up time of patients at the time of analysis was 54.99+/-15.53 months. The rate of lost follow-up was 11.55%. Cumulative 6-year RD rates were 1.16% in the full study group, 1.90% in the male subgroup, and 0.56% in the female subgroup at the end of the follow-up period. Gender distribution had a significant influence on the occurrence of RD after CE (P<0.001). Factors that were found to have a significant effect on the risk of pseudophakic RD included age under 50 years (P = 0.002), AL (P<0.001), and history of RD (P = 0.003). Surgical types (extracapsular vs. phacoemulsification) were not correlated significantly with RD, and neither were such systemic diseases as diabetes and hypertension. Subgroup analysis indicated that the significance of age, AL, and history of RD as risk factors persisted in the male subgroup but not in the female subgroup. CONCLUSIONS: The impact of axial myopia, age, and RD history as risk factors for pseudophakic RD was seen predominantly in males.

Axial myopia is an extremely significant risk factor for young-aged pseudophakic retinal detachment in taiwan.

PURPOSE: To investigate the possible risk factors of retinal detachment (RD) after cataract extraction and intraocular lens implantation in a geographic defined racially uniform population. METHODS: Submitted claim records and charts of 9398 insurance beneficiaries who underwent cataract extraction and intraocular lens implantation between August 1999 and December 2001 were consecutively collected from the Bureau of National Health Insurance (BNHI). At the end of 2003, any ophthalmologic diagnosis and related treatment based on procedure and diagnosis codes listed in physician bills were evaluated. RESULTS: The cumulative risk of RD in our study group was 0.76% at the end of follow-up. The mean follow-up time was 36.92 +/- 8.89 months. Sex distribution had no significant effect on the occurrence of RD after cataract extraction, whereas age distribution showed significant influence on the risk of RD after cataract surgery (P = 0.0307), as did the history of RD (P < 0.0001) and Nd-YAG laser posterior capsulotomy (P = 0.0001). Axial length also had a significant effect on the risk of RD after cataract extraction (P < 0.0001). The longer the axial length, the more impact on the risk of RD carried by young age. CONCLUSIONS: The results showed that axial myopia is an extremely significant risk factor for young-aged pseudophakic RD in Taiwan.