retinal toxicity
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2022 ◽  
Author(s):  
Zhuhong Zhang ◽  
Laien Zhao ◽  
Yuanyuan Ma ◽  
Jia Liu ◽  
Yanmei Huang ◽  
...  

Abstract Background: Silica nanoparticles (SiO2 NPs) are extensively applied in the biomedical field. The increasing medical application of SiO2 NPs has raised concerns about their safety. However, studies on SiO2 NP-induced retinal toxicity are lacking.Methods: We investigated the retinal toxicity of SiO2 NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO2 NPs with different sizes was assessed in R28 human retinal precursor cells by determining the ATP content and LDH release. The cell morphologies and nanoparticle distributions in the cells were analyzed by phase-contrast microscopy and transmission electron microscopy, respectively. The mitochondrial membrane potential was examined by confocal laser scanning microscopy. The retinal toxicity induced by SiO2 NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO2 NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored.Results: The 15-nm SiO2 NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO2 NPs induced retinal toxicity in vivo, as demonstrated by increased cell death in the retina, TUNEL-stained retinal cells, retinal ganglion cell degeneration, glial cell activation, and inflammation. In addition, The SiO2 NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H2DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO2 NPs.Conclusions: These results provide evidence that SiO2 NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity.


2022 ◽  
pp. 106073
Author(s):  
Xin Chen ◽  
Tiantong Qiu ◽  
Peng Xiao ◽  
Wenhua Li
Keyword(s):  

Author(s):  
Anna Sharabura ◽  
John Chancellor ◽  
M. Zia Siddiqui ◽  
David Henry ◽  
Ahmed B. Sallam

2021 ◽  
pp. 247412642110445
Author(s):  
Tamara L. Lenis ◽  
Benjamin W. Botsford ◽  
David Sarraf ◽  
Thanos D. Papakostas

Purpose: This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene. Methods: Case report. Results: A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the CRB1 gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area. Conclusions: This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.


2021 ◽  
Vol 62 (14) ◽  
pp. 8
Author(s):  
Jessica V. Kaczmarek ◽  
Carley M. Bogan ◽  
Janene M. Pierce ◽  
Yuankai K. Tao ◽  
Sheau-Chiann Chen ◽  
...  

Author(s):  
Olga Araújo ◽  
Laura Pelegrín ◽  
Gerard Espinosa ◽  
Ricard Cervera
Keyword(s):  

Author(s):  
Dandyala Pavan Kalyan ◽  
Gajula Sri Teja ◽  
Kallem Sharat Venkat Reddy ◽  
Marina D’souza

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, which affects the major organs in the human body. Pathophysiology of SLE is unknown. It mainly affects the joints, and restricts their movement. Hydroxychloroquine (HCQ) an anti-malarial drug is used as the first line of drugs used to treat SLE. The major adverse effect of this drug is irreversible retinopathy. The aim of the study was to evaluate the incidence and prevalence of retinopathy in patients with long-term usage of hydroxychloroquine (for more than 1 year).Methods: In patients with SLE, we recorded a review on HCQ induced toxicity among those taking it for longer period (>1 year). All the patients were above 18 years of age. A total data of 210 patients suffering from SLE and taking HCQ for more than one year was collected. Patients were categorized according to gender and dose pattern. Out of 210 patients, 0 patients were found to be retinal toxic induced by HCQ.Results: Suitable statistical tools were used and data was analysed which showed the incidence and prevalence of HCQ induced toxicity. With the results of our study we can understand that incidence and prevalence rates were very low among the subjects.Conclusions: HCQ is said to reduce the risk of disease remission, improves survival, minimizes the risks of vital organ damage, reduces the frequency of flares and has a protective effect on cardiovascular health.  HCQ medication is usually well tolerated.  But irreversible retinopathy is the major effect on long term use of HCQ.  The present study concludes that in the nominal daily dose of 200mg did not reveal any signs of retinal toxicity in 100% of the population tested within 5 years of HCQ treatment suggesting that the toxicity is rare and can be prevented by reducing the dose of the drug.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Che-Hung Shen ◽  
Chi-Che Hsieh ◽  
Kuan-Ying Jiang ◽  
Chih-Yu Lin ◽  
Nai-Jung Chiang ◽  
...  

Abstract Background Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that mediate AUY922-induced retinal toxicity remain undescribed. Methods The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)‑based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches. Results Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922. Conclusions Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity.


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