Generation of an induced pluripotent stem cell line (SJTUGHi001-A) from a patient with Retinitis Pigmentosa carrying c.77C > T mutation in RAX2 gene.

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinopathy resulting in irreversible loss of vision. Mutations in RAX2 gene has been related to RP with mechanisms unclear. Here, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a RP patient carrying c.77C > T mutation in RAX2 gene. This cell line was induced by integration-free episomal vectors and validated for pluripotency and differentiation capacity, which may serve as a model to study the role of RAX2 in RP pathogenesis.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Thermal Stability of Au Rhombic Dodecahedral Nanocrystals Can Be Greatly Enhanced by Coating Their Surface with an Ultrathin Shell of Pt.

Rhombic dodecahedral nanocrystals have been considered particularly difficult to synthesize because they are enclosed by {110}, a low-index facet with the greatest surface energy. Recently, we demonstrated the use of seed-mediated growth for the facile and robust synthesis of Au rhombic dodecahedral nanocrystals (AuRD). While the unique shape and surface structure of AuRD are desirable for potential applications in plasmonics and catalysis, respectively, their high surface energy makes them highly susceptible to thermal degradation. Here we demonstrate that it is feasible to greatly improve the thermal stability with some sacrifice to the plasmonic properties of the original AuRD by coating their surface with an ultrathin shell made of Pt. Our in situ electron microscopy analysis indicates that the ultrathin Pt coating can increase the thermal stability from 60 up to 450 °C, a trend that is also supported by the results from a computational study.

A Bibliometric Analysis of Uveitis in the Past 20 Years.

PURPOSE: To assess the quantity and quality of global research on uveitis, visualize the research hotspots, and reveal the study trends in uveitis. METHODS: This bibliometric analysis was performed with the data obtained from the Web of Science core collection (WoSCC) database and Scopus. Bibliometrix and VOSviewer were used to analyze and visualize study trends and hotspots. Citespace was used to conduct the cooperation and co-citation network analysis. RESULTS: A total of 5837 and 7195 documents were exported for further analysis in WoSCC and Scopus, respectively. The USA has published the most articles related to uveitis (1627, 27.87%, WoS; 1979, 27.51%, Scopus) and accounted for the most frequency of total citations (42345 times total citations 35 900 times without self-citations in WoSCC database). Most of the papers focusing on uveitis were published in Ocular Immunology and Inflammation (761, 13.04% within WoS; 793, 11.02% within Scopus). Additionally, novel biotherapy is the hotspot of uveitis research which also may be a sustained research interest in the future. CONCLUSIONS: An increasing trend of publications was found in uveitis research. The USA was the leading contributor in this field, and it was the center of cooperation network. Our study provided an overview of uveitis research, which may serve as a valuable reference and guide for stakeholders interested in uveitis.

Volume electron microscopy reconstruction uncovers a physical barrier that limits virus to phloem.

Most plant reoviruses are phloem-limited, but the mechanism has remained unknown for more than half a century. Southern rice black-streaked dwarf virus (Fijivirus, Reoviridae) causes phloem-derived tumors, where its virions, genomes, and proteins accumulate, and it was used as a model to explore how its host plant limits the virus within its phloem. High-throughput volume electron microscopy revealed that only sieve plate pores and flexible gateways rather than plasmodesmata had a sufficiently large size exclusion limit (SEL) to accommodate virions and potentially serve as pathways of virion movement. The large SEL gateways were enriched within the proliferated sieve element (SE) layers of tumors. The lack of such connections out of the SE-enriched regions of tumors defined a size-dependent physical barrier to high flux transportation of virions. A working model is proposed to demonstrate the mechanism underlying limitation of virus within phloem.

Nomogram of uveal melanoma as prediction model of metastasis risk.

Background: Since the poor prognosis of uveal melanoma with distant metastasis, we intended to screen out possible biomarkers for uveal melanoma metastasis risk and establish a nomogram model for predicting the risk of uveal melanoma (UVM) metastasis. Methods: Two datasets of UVM (GSE84976, GSE22138) were selected. Data was analyzed by R language, CTD database and GEPIA. Results: The co-upregulated genes of two datasets, HTR2B, CHAC1, AHNAK2, and PTP4A3 were identified using a Venn diagram. These biomarkers are combined with clinical characteristics, and Lasso regression was conducted to filter the metastasis-related biomarkers. HTR2B, CHAC1, AHNAK2, PTP4A3, tumor thickness, and retinal detachment (RD) were selected to establish the nomogram. Conclusion: Our study provides a comprehensive predictive model and personalized risk estimation tool for assessment of 3-year metastasis risk of UVM with a better accuracy.

The association between glaucoma and all-cause mortality in middle-aged and elderly Chinese people: results from the China Health and Retirement Longitudinal Study.

OBJECTIVES: This population-based, prospective cohort study investigated the association between glaucoma and mortality in older adults. METHODS: Participants aged 45 years or older at baseline (47.9% male) were enrolled in 2011 for the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was observed during 7 years of follow-up. The baseline data were collected in the 2011 CHARLS, and participants were followed up for 7 years (until 2018). The risk of all-cause mortality was investigated using Cox proportional-hazards regression with age as the time scale, adjusting for significant risk factors and comorbid conditions. RESULTS: Among the 14,803 participants included, the risk of all-cause death was significantly higher among people with glaucoma than among those without glaucoma, after adjustment for other confounders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04 to 2.03). In a subgroup analysis based on the mean age of death, among those who were 75 years and older (n=1,231), the risk of all-cause death was significantly higher in patients with glaucoma than in those without glaucoma (HR, 1.89; 95% CI, 1.24 to 1.89). CONCLUSIONS: Participants with glaucoma had a higher risk of all-cause mortality, especially those aged 75 years and above. Our findings revealed potential mechanisms underlying an association between glaucoma and all-cause mortality. They also highlighted the importance of glaucoma management to prevent premature death in middle-aged and older adults.

Contribution of CKD to mortality in middle-aged and elderly people with diabetes: the China Health and Retirement Longitudinal Study : CKD was a chronic stressor for diabetics.

BACKGROUND: The contribution of chronic kidney disease (CKD) to mortality in diabetic patients is unclear. This study aimed to explore the association between diabetics with CKD and mortality in middle-aged and elderly people of different ages. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study, including 1,715 diabetic individuals, 13.1% of whom also had CKD. Diabetes and CKD were assessed by combining the physical measurements and self-reports. We fitted Cox proportional hazards regression models to examine the effect of diabetics with CKD on mortality in middle-aged and elderly people. The risk factors for death were further predicted based on age stratification. RESULTS: The mortality rate of diabetic patients with CKD (29.3%) was increased as compared to that of diabetic patients without CKD (12.4%). Diabetics with CKD were at a higher risk of all-cause mortality than those without CKD, with a hazard ratio of 1.921 (95% CI: 1.438, 2.566). Additionally, for participants 45 to 67 years of age, the hazard ratio was 2.530 (95% CI: 1.624, 3.943). CONCLUSIONS: Our findings suggested that, for diabetics, CKD was a chronic stressor that led to death in middle-aged and elderly people, especially among participants aged 45 to 67 years.

Association between previous cataract surgery and cognition among middle-aged and older Chinese: the China health and retirement longitudinal study (CHARLS).

BACKGROUND: Cataract is the primary cause of blindness globally, and surgery offers the only method by which to remove cataracts. We aimed to examine whether previous cataract surgery is associated with cognitive function. METHODS: Our study included 13,824 participants. Data from the baseline of the China Health and Retirement Longitudinal Study (CHARLS) were used. The participants were categorized into two groups: with and without previous cataract surgery. Weighted multiple linear regression was used to obtain the ß and 95% confidence intervals (CI). RESULTS: The participants who had previous cataract surgery (n = 261) scored lower in cognition, including both memory and mental state, than those without previous cataract surgery. After adjusting for socioeconomic factors and metabolic measures, a negative association was evident between previous cataract surgery and cognition (ß = -0.647, 95% CI: -1.244, - 0.049). Furthermore, the participants who were older and female demonstrated a decline in cognition, while living in cities and having higher levels education were associated with higher cognition. CONCLUSIONS: Better cognitive function was associated with less previous cataract surgery or cataract occurrence. This suggests that a period of vision loss due to cataract leads to cognitive decline, however further studies are need to dissect the impact of vision loss and cataract surgery on cognitive decline.

The association between obesity and glaucoma in older adults: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVES: This study evaluated the association between obesity and glaucoma in middle-aged and older people. A population-based retrospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study. METHODS: Glaucoma was assessed via self-reports. Multivariate logistic regression analysis and a Cox proportional hazards model were used to assess the relationship between obesity and glaucoma risk. RESULTS: Older males living in urban areas who were single, smokers, and non-drinkers were found to have a significantly higher incidence of glaucoma (all p<0.05). Diabetes, hypertension, and kidney disease were also associated with higher glaucoma risk, while dyslipidemia was associated with lower risk (all p<0.05). After the model was adjusted for demographic, socioeconomic, and health-related variables, obesity was significantly associated with a 10.2% decrease in glaucoma risk according to the Cox proportional hazards model (hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.97) and an 11.8% risk reduction in the multivariate logistic regression analysis (odds ratio, 0.88; 95% CI, 0.80 to 0.97). A further subgroup analysis showed that obesity was associated with a reduced risk of glaucoma in people living in rural areas, in smokers, and in those with kidney disease (all p<0.05). Obesity also reduced glaucoma risk in people with diabetes, hypertension, or dyslipidemia more than in healthy controls (all p<0.05). CONCLUSIONS: This cohort study suggests that obesity was associated with a reduced risk of glaucoma, especially in rural residents, smokers, and people with kidney disease. Obesity exerted a stronger protective effect in people with diabetes, hypertension, or dyslipidemia than in healthy people.

Bifidobacterium promotes retinal ganglion cell survival by regulating the balance of retinal glial cells.

INTRODUCTION: Optic nerve injury is a leading cause of irreversible blindness worldwide. The retinal ganglion cells (RGCs) and their axons cannot be regenerated once damaged. Therefore, reducing RGC damage is crucial to prevent blindness. Accordingly, we aimed to investigate the potential influence of the gut microbiota on RGC survival, as well as the associated action mechanisms. METHODS: We evaluated the effects of microbiota, specifically Bifidobacterium, on RGC. Optic nerve crush (ONC) was used as a model of optic nerve injury. Vancomycin and Bifidobacterium were orally administered to specific pathogen-free (SPF) mice. RESULTS: Bifidobacterium promoted RGC survival and optic nerve regeneration. The administration of Bifidobacterium inhibited microglia activation but promoted Müller cell activation, which was accompanied by the downregulation of inflammatory cytokines and upregulation of neurotrophic factors and retinal ERK/Fos signaling pathway activation. CONCLUSIONS: Our study demonstrates that Bifidobacterium-induced changes in intestinal flora promote RGC survival. The protective effect of Bifidobacterium on RGC can be attributed to the inhibition of microglia activation and promotion of Müller cell activation and the secondary regulation of inflammatory and neurotrophic factors.

A DNA-Schiff base functional nanopore sensing platform for the highly sensitive detection of Al3+ and Zn2+ ions.

The combination of DNA nanotechnology and nanopore sensing technology has greatly promoted research on target molecule or ion detection. The large solid-state nanopores/nanochannels show better mechanical stability and reproducibility, but metal ion detection in the large nanopores with diameters of hundreds of nanometers or several micrometers is rarely reported. Hence, it is meaningful and urgent to develop a large nanopore-based sensing platform for the detection of metal ions. Herein, we employed a salicylic aldehyde-modified DNA network in conjunction with a glass nanopipette (GN) with a diameter of hundreds of nanometers as a sensing platform for the detection of target metal ions. Upon the addition of different receptors with the amino group, the salicylic aldehyde could in situ specifically recognize and bind with Zn2+ and Al3, forming Schiff base-metal ion complexes at the four vertices of one face per nanocube unit. The steric hindrance effect of multiple Schiff bases and metal ion complexes leads to the blockage of internal structure and decrease of ion current in the GN. Owing to this signal amplification strategy, the detection limit of the target metal ion reaches a level of fM in the GN with a diameter of about 300 nm. In the future, this functional nanopore sensing platform is expected to realize highly sensitive detection for more biological metal ions by choosing appropriate receptors.

An integrative method for evaluating the biological effects of nanoparticle-protein corona.

BACKGROUND: Nanoplastics in the environment can enter the human body through gastrointestinal intake, dermal contact, and pulmonary inhalation, posing a threat to human health. Protein molecules in body fluids will quickly adsorb on the surfaces of the nanoplastics, forming a protein corona, which has implications for the interaction of the nanoplastics with cells and the metabolic pathways of the nanoplastic within cells. For years, practical tools such as dynamic light scattering, transmission electron microscopy, and liquid chromatography have been developed to understand the protein corona of nanoparticles (NPs), either in vitro or in cellular or molecular level. However, an integrated approach to understand the nanoparticles-protein corona is still lacking. METHODS: Using the most frequently observed environmental nanoplastics, polystyrene nanoplastics (PS), as a standard, we established an integrative structural characterization platform, a biophysical and biochemical evaluation method to investigate the effect of surface charge on protein corona composition. The cellular and molecular mechanisms were also explored through in vitro cellular experiments. RESULTS: The first integrative method for characterizing biological properties of NPs-protein corona has been established. This method comprehensively covers the critical aspects to understand NPs-protein corona interactions, from structure to function. CONCLUSIONS: The integrative method for nanoplastics microstructure characterization can be applied to the structural characterization of nanoparticles in nanoscale, which is of universal significance from in vitro characterization to cellular experiments and then to molecular mechanism studies. GENERAL SIGNIFICANCE: This strategy has high reliability and repeatability and can be applied both in environment and nanomedicine safety assessment.

The Toxic Effects of Cu and CuO Nanoparticles on Euplotes aediculatus.

The single-celled eukaryote Euplotes aediculatus was chosen to test and compare the toxic effects of Cu and CuO nanoparticles (NPs). The antioxidant enzymatic activity, morphological changes, and functional groups on the membrane were determined using spectrophotometry, microscopy, and Fourier transform infrared spectroscopy after NPs treatment. The toxicity of the NPs to cells was dose-dependent, and the 24 h-LC50 values of the CuNPs and CuONPs were 0.46 µg/L and 1.24 × 103 µg/L, respectively. These NPs increased the activities of superoxide dismutase, glutathione peroxidase, and catalase and destroyed the cell structure; moreover, the CuNPs were more toxic than the CuONPs. In addition to the higher enzymatic activity, CuNPs also caused nucleoli disappearance, chromatin condensation, and mitochondrial and pellicle damage. The oxidization of the functional groups of the membrane (PO2 - , C-O-C, and δ(COH) of carbohydrates) also confirmed the severe damage caused by CuNPs. Our study showed that oxidative stress and organelle destruction played important roles in the toxic effects of these NPs on this protozoan. Compared with other aquatic organisms, E. aediculatus can be considered a potential indicator at the preliminary stage of environmental pollution.

One-Year Results of a Multicenter Study: Intraocular Pressure-Lowering Effect of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Cases of Advanced Primary Angle-Closure Glaucoma With Cataract.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of the combination of phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes of advanced primary angle-closure glaucoma (PACG) with cataract. DESIGN: Multicenter observational study. METHODS: We enrolled 83 eyes of 83 patients with advanced PACG who received combined PEI+GSL+GT at 8 ophthalmic institutes. Each patient was assessed before treatment and at 1, 7 days, 1, 3, 6, and 12 months postsurgery. The criteria for complete success were IOP within 6 to 18 mm Hg and at least 20% of reduction in IOP from baseline without ocular hypotensive medications or reoperation. The definition of qualified success was similar to that of complete success, except for the need for ocular hypotensive medications. The potential prognostic factors for surgical success were investigated using a multivariate logistic model. RESULTS: All participants completed 1 year of follow-up. Complete and qualified success were achieved in 74 (89.1%) and 79 (95.2%) of 83 eyes, respectively. The mean preoperative and postsurgical IOPs were 27.4±7.3 and 14.2±2.6 mm Hg, respectively. Participants used an average of 2.0 and 0.3 types of ocular hypotensive medications before and after surgery, respectively. The chief complications included hyphema (n=9), IOP spike (n=9), and corneal edema (n=8). None of the eyes required reoperation or developed vision-threatening complications. Multivariate analysis showed that older age was associated with a higher probability of complete success (odds ratio=1.13; 95% CI: 1.02-1.25; P=0.020). CONCLUSIONS: The 1-year results of combination of PEI+GSL+GT in treating advanced PACG cases with cataract appear to be safe and effective. Further large-scale multination and multicenter studies are warranted.

Prevalence and Risk Factors of Glaucoma Among Chinese People From the China Health and Retirement Longitudinal Study.

PRCIS: This study demonstrated the prevalence of self-reported glaucoma and its strong association with preexisting systemic chronic diseases in China using the baseline data from China Health and Retirement Longitudinal Study (CHARLS), a nationwide population-based cohort. PURPOSE: The purpose of this study is to estimate the prevalence of self-reported glaucoma and its risk factors using data from the CHARLS. MATERIALS AND METHODS: Data on age, sex, area of residence, education, marital status, health-related behaviors, and preexisting comorbidities for this cross-sectional study were retrieved from the CHARLS for 17,713 subjects who completed a questionnaire between June 2011 and March 2012. The prevalence of glaucoma was estimated, and a multivariate weighted analysis was performed to estimate the odds ratios (ORs) of its risk factors. RESULTS: Of 16,599 respondents (93.7%) who answered questions regarding glaucoma and their history of systemic chronic diseases, 314 (1.89%) reported having glaucoma before the index date. Qinghai and Beijing had the highest prevalence of glaucoma in China. Glaucoma was significantly associated with hypertension [OR: 1.362; 95% confidence interval (CI), 1.801-2.470], diabetes (OR: 2.597; 95% CI, 1.661-10.207), dyslipidemia (OR: 1.757; 95% CI, 1.157-3.650), lung disease (OR: 2.098; 95% CI, 1.674-6.527), stroke (OR: 5.278; 95% CI, 1.094-25.462), heart disease (OR: 1.893; 95% CI, 1.237-3.363), and health-related behaviors such as smoking and alcohol consumption after adjusting for age, sex, area, education, marital status, and medical insurance. CONCLUSIONS: Geographic variation in the prevalence of self-reported glaucoma and its strong association with preexisting systemic chronic diseases were observed, suggesting that in addition to ophthalmological examinations, regular physical examinations are necessary for glaucoma patients, especially in areas of high incidence. Appropriate strategies to improve preventive measures for glaucoma are recommended for the Chinese population.

Effects of the continuous pulsation regeneration on the soot combustion in diesel particulate filter for heavy-duty truck.

Continuous pulsation regeneration combustion of soot is employed for sine and cosine simulation study. Data showed that pressure uniformity of sine condition is better than that of cosine condition with the maximum pressure difference of 4353.5 Pa under the same simulation boundary conditions. The maximum regeneration temperature under cosine pressure is 46.12 K which is higher than that in sine form. Regeneration combustion reaction zone tends to be more stable laminar flow and Reynolds number of sine condition is 435.23 less than that of under cosine condition. The maximum Stanton number of cosine pressure condition is 3.67 and that of sine pressure condition is 5.15, which investigates heat transfer capacity of the sine pressure condition is better than that of the pressure of cosine form. The regeneration efficiency of inlet gradually increased from the minimum regeneration efficiency 74.18%-88.45% of sine and cosine. The soot under both pressure forms has achieved complete regeneration and the regeneration efficiency has exceeded 88% of porous medium filter body section. The soot regeneration combustion efficiency of the porous media filter section and outlet section is more sufficient under sine condition and the heat carried by the fluid can maintain the soot regeneration.

Visual impairment and depression in China: a 7-year follow-up study from national longitudinal surveys.

OBJECTIVES: To explore the longitudinal association between visual impairment (VI) and depression among adults 45 years and older in China based on a nationally representative follow-up dataset. SETTING: Participants in China from the China Health and Retirement Longitudinal Study were included. PARTICIPANTS: A total of 6748 participants from two waves of the China Health and Retirement Longitudinal Study 2011-2018 were included for analysis by age group. PRIMARY AND SECONDARY OUTCOME MEASURES: VI and depression were defined by self-diagnosis and the Center for Epidemiological Studies Depression Scale-10, respectively. Lagged dependent variable regression models with ordinary least squares estimation were used to evaluate the association between VI and depression. Age was divided into three groups, that is, 45-54, 55-64, and 65 years and older, to explore the relationship between VI and depression in different age groups. RESULTS: In our study sample, VI remarkably predicted an increase in depressive scores. The magnitude of depressive scores increased among those with VI points greater than 3.517 (ß=3.517; 95% CI=2.697 to 4.331) points than those without VI in the 7-year follow-up. Significant relationships were also found between VI and depression in the three age groups in the sensitivity analysis. CONCLUSION: VI was associated with an increase in depression scores over a 7-year period. Female respondents, low educational attainment and high alcohol intake significantly predicted an increase in depressive status.

HMGB2 causes photoreceptor death via down-regulating Nrf2/HO-1 and up-regulating NF-κB/NLRP3 signaling pathways in light-induced retinal degeneration model.

In the pathogenesis of retinal degenerative diseases, oxidative stress is a key driver leading to photoreceptor death and eventually vision loss. Currently, there are no effective therapies available to rescue photoreceptors in these diseases. High-mobility group box 2 (HMGB2), a pro-inflammatory factor and damage-associated molecular patterns (DAMPs), has been proven to mediate various inflammatory diseases, but its role in retinal degenerative diseases, especially in retinal inflammation and photoreceptor degeneration, still remains unknown. In this study, we assessed the localization and function of HMGB2 under oxidative stress and explored the underlying mechanisms in a mouse model of light-induced retinal damage (LIRD). The results showed that increased oxidative stress, the photoreceptors death, as well as the pyroptosis-related proteins were evidenced in mice retina after light exposure. HMGB2 protein was predominantly expressed in the outer nuclear layer (ONL), which was translocated to the cytoplasm and released after injury. The mechanistic effect of HMGB2 was studied in the 661w cell line treated with H2O2, showing that exogenous recombinant HMGB2 protein reduced the expressions of the antioxidant protein nuclear erythroid factor 2-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1), and induced NF-κB/NLRP3 signaling pathway. HMGB2 knockdown increased cell viability, up-regulated the expressions of Nrf2 and HO-1, down-regulated the expressions of pyroptosis-related proteins in H2O2-treated 661w cells; and also prevented photoreceptors loss and maintained ONL in mice model of LIRD. The present study proposed HMGB2 as a potential therapeutic target for treatment of retinal degenerative diseases.

Malondialdehyde-Modified Photoreceptor Outer Segments Promote Choroidal Neovascularization in Mice.

Purpose: This study aimed to establish a novel choroidal neovascularization (CNV) mouse model through subretinally injecting malondialdehyde (MDA)-modified photoreceptor outer segments (POS), which was more consistent with the pathogenesis of wet age-related macular degeneration (AMD). Methods: MDA-modified POS were subretinally injected in C57BL/6J mice. Four weeks later, to assess the volume of CNV and the morphology of retinal pigment epithelium (RPE), isolectin B4 and zonula occludens-1 antibody were used for immunostaining. Fundus fluorescent angiography and optical coherence tomography imaging were used to describe the morphologic features of CNV. Transepithelial resistance was measured on polarized ARPE-19 cells. Vascular endothelial growth factor levels in the cell culture medium were detected by enzyme-linked immunosorbent assay. The protein and messenger RNA expression levels of autophagy markers were measured using Western blot and quantitative polymerase chain reaction. Results: CNV and RPE atrophy were successfully induced in the mouse model. MDA-modified POS also significantly increased the expression of vascular endothelial growth factor and disrupted cell junctions in RPE cells. In addition, MDA-modified POS induced autophagy-lysosomal impairment in RPE cells. Conclusions: Subretinal injection of MDA-modified POS may generate a feasible CNV model that simulates the AMD pathological process. Translational Relevance: This study expands the understanding of the role of MDA in AMD pathogenesis, which provides a potential therapeutic target of AMD.