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Knockdown of FOXO6 inhibits high glucose–induced oxidative stress and apoptosis in retinal pigment epithelial cells
摘要： Oxidative stress and apoptosis in retinal pigment epithelium cells are involved in the pathogenesis of diabetic retinopathy (DR). Forkhead box class O 6 (FOXO6) is a member of the FOXO family that can regulate diabetes‐induced oxidative stress. However, the role of FOXO6 in DR has not been clarified. The aim of the present study was to investigate the effects of FOXO6 on high glucose (HG)‐induced oxidative stress and apoptosis in ARPE‐19 cells. The results showed that FOXO6 was overexpressed in clinical vitreous samples from DR patients and in HG‐induced ARPE‐19 cells. Knockdown of FOXO6 by small interfeing RNA targeting FOXO6 (si‐FOXO6) mitigated the HG‐induced the production of reactive oxygen species and malondialdehyde, as well as the inhibition of superoxide dismutase activity. Knockdown of FOXO6 reduced the rate of cell apoptosis in HG‐induced ARPE‐19 cells. The increase in bax expression and decrease in bcl‐2 expression caused by HG stimulation were reversed by si‐FOXO6 transfection. Furthermore, knockdown of FOXO6 enhanced the activation of Akt/Nrf2 pathway in HG‐stimulated ARPE‐19 cells. Taken together, suppression of FOXO6 protects ARPE‐19 cells from HG‐induced oxidative stress and apoptosis, which is in part mediated by the activation of Akt/Nrf2 pathway.
关键词： Akt/Nrf2 pathway,oxidative stress,retinal pigment epithelium cells,forkhead box class O 6,diabetic retinopathy,apoptosis
更新于2025-09-04 15:30:14
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Lipofuscin-mediated photodynamic stress induces adverse changes in nanomechanical properties of retinal pigment epithelium cells
摘要： Retinal pigment epithelium (RPE) is an important part of the blood-retina barrier (BRB) that separates the retina from the choroid. Although melanin granules contribute to the mechanical stability of the BRB complex, it is unknown if the age pigment lipofuscin affects mechanical properties of the tissue. To address this issue the effect of sub-lethal photic stress mediated by phagocytized lipofuscin granules, isolated from RPE of human donors, on morphology and mechanical properties of ARPE-19 cells was investigated. Nanomechanical analysis using atomic force spectroscopy revealed that irradiation of cells containing lipofuscin granules with blue light induced significant softening of the cells, which was accompanied by substantial reorganization of the cell cytoskeleton due to peroxidation of cellular proteins. Our results indicate that lipofuscin-mediated photic stress can cause significant modification of the RPE cells with the potential to disturb biological function of the BRB complex.
关键词： photic stress,lipofuscin,Retinal pigment epithelium,nanomechanical properties,blood-retina barrier
更新于2025-09-04 15:30:14
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Perception of Haidinger Brushes in Macular Disease Depends on Macular Pigment Density and Visual Acuity
摘要： PURPOSE. To optimize the perceptibility of Haidinger brushes (HB) and to investigate its association with visual acuity and macular pigment density. METHODS. In this prospective cross-sectional study, each subject underwent best-corrected visual acuity (BCVA) testing, funduscopy, and assessment of macular pigment optical density (MPOD) using the two-wavelength fundus autofluorescence method. Haidinger brush visibility was tested with a rotating linear polarizer and a controllable three-color light-emitting diode (LED) panel as light source. A simple model of macular pigment absorption was used to predict HB visibility as a function of stimulus wavelength and MPOD. RESULTS. All control eyes (n ? 92) and 34% of the 198 eyes of subjects with macular disease (age-related macular degeneration, n ? 40; macular telangiectasia type 2, n ? 52; Stargardt disease, n ? 58; other retinal dystrophies, n ? 48) perceived HB when an optimized test setup (464-nm LED light) was applied. The degree of psychophysical perception and the dependency on different wavelengths were in accordance with the absorptance model. In eyes of subjects with macular disease, minimum thresholds of MPOD and BCVA required for HB perception were identified. Subjects with macular telangiectasia type 2 showed lowest values of MPOD and were mostly unable to perceive HB despite relatively preserved BCVA. CONCLUSIONS. Macular pigment and a relatively preserved foveal function are necessary for the perception of HB. Haidinger brushes are usually not perceived by subjects with macular telangiectasia type 2, likely due to their characteristic foveal depletion of macular pigment.
关键词： entoptic phenomenon,Haidinger brush,macular pigment,visual acuity,macular disease
更新于2025-09-04 15:30:14
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A two-year study of diffused retinal pigment epitheliopathy treated with half-dose photodynamic therapy guided by simultaneous angiography and optical coherence tomography
摘要： Objectives Diffused retinal pigment epitheliopathy (DRPE) is not necessarily the same as chronic central serous chorioretinopathy (CSC), but a severe subgroup under the umbrella of chronic CSC. This study was to evaluate the efficacy and safety of half-dose PDT treating DRPE. Methods A retrospective case series design was used. Forty-eight consecutive patients (48 eyes) with DRPE treated with half-dose PDT underwent follow-up at baseline, 3 months, 6 months, 12 months and 24 months. Simultaneous FA, ICGA and OCT were used for the treatment and follow-up. The primary outcomes were the subretinal fluid and best-corrected visual acuity in optical coherence tomography. Results Complete fluid absorption was achieved in 95.8% of eyes at 3 months and 100.0% of eyes at 24 months. The baseline logarithm of the minimum angle of resolution (logMAR) BCVA, which was 0.51 ± 0.36, significantly improved to 0.43 ± 0.38 (p < 0.001) at 6 months. The boost continued to 0.29 ± 0.37 (p < 0.001) at 12 months and 0.19 ± 0.39 (p < 0.001) at 24 months. The integrities of the ellipsoid zone (EZ) and interdigitation zone (IZ) improved throughout. Regression analyses showed the BCVA in logMAR was inversely correlated with the EZ (p < 0.01) and IZ (p < 0.01). The recurrence rate was 6.3%. No severe complications were witnessed. Conclusions In 48 eyes with DRPE, simultaneous angiography and OCT facilitated a more comprehensive guidance for half-dose PDT treatment and follow-up. The BCVA improvement occurred at 6 months, which may be attributed to the restoration of the outer retinal structure.
关键词： chronic central serous chorioretinopathy,half-dose photodynamic therapy,Diffused retinal pigment epitheliopathy,angiography,CSC,optical coherence tomography,OCT,DRPE,PDT
更新于2025-09-04 15:30:14
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Melanin Pigmentation in Rat Eyes: In Vivo Imaging by Polarization-Sensitive Optical Coherence Tomography and Comparison to Histology
摘要： The purpose of this study was to demonstrate polarization-sensitive optical coherence tomography (PS-OCT) for imaging pigmented structures in the posterior eye segments of albino and pigmented rats and to correlate depolarization contrast of the retinal pigment epithelium (RPE) and choroid in in vivo PS-OCT to melanin pigmentation detected in postmortem histologic serial sections. In vivo three-dimensional PS-OCT imaging was performed in adult albino and pigmented rat eyes at 70-kHz A-line rate. Degree of polarization uniformity (DOPU) fundus maps and radial DOPU pro?les were generated. Postmortem histomorphologic analysis was performed in order to investigate melanin pigmentation of the RPE and choroid. Fundus pigmentation maps were extracted from histologic serial sections. Pigmentation pro?les were correlated to DOPU pro?les of the same eyes. Strong depolarization was found in the RPE/choroid complex of pigmented rats, whereas the same structures exhibited uniform polarization in albino rats. The difference between the depolarization characteristics between albino and pigmented animals was statistically signi?cant. In the fundus pigmentation maps, optical pigment density was zero in albino rat eyes. In pigmented rat eyes, a strong negative correlation between optical pigment density and DOPU was observed. This in vivo and ex vivo investigation of posterior rat eyes indicates that melanin is the cause of depolarization in retinal PS-OCT images. It further demonstrates that melanin pigmentation in the RPE and choroid can be quanti?ed via depolarization imaging and therefore suggests that PS-OCT is a useful tool for the noninvasive quantitative assessment of pigmentary changes in vision-threatening diseases such as age-related macular degeneration.
关键词： choroid,melanin,optical coherence tomography,depolarization,retinal pigment epithelium,polarization sensitive devices
更新于2025-09-04 15:30:14