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Redox Biology Nov 2023Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is...
Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.
Topics: Animals; Mice; Humans; Toxoplasmosis, Ocular; Ferroptosis; Toxoplasma; Chorioretinitis; Retina; Iron
PubMed: 37738924
DOI: 10.1016/j.redox.2023.102890 -
Journal of Proteome Research Feb 2024Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting... (Review)
Review
Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting a promising alternative to solid tissue biopsies. The advantages of liquid biopsies include sampling the eye without causing irreversible functional damage, potentially better reflecting tissue heterogeneity, collecting samples in an outpatient setting, monitoring therapeutic response with sequential sampling, and even allowing examination of disease mechanisms at the cell level in living humans, an approach that we refer to as TEMPO (Tracing Expression of Multiple Protein Origins). Liquid biopsy proteomics has the potential to transform molecular diagnostics and prognostics and to assess disease mechanisms and personalized therapeutic strategies in individual patients. This review addresses opportunities, challenges, and future directions of high-resolution liquid biopsy proteomics in ophthalmology, with particular emphasis on the large-scale collection of high-quality samples, cutting edge proteomics technology, and artificial intelligence-supported data analysis.
Topics: Humans; Ophthalmology; Proteomics; Artificial Intelligence; Liquid Biopsy; Proteins; Biopsy
PubMed: 38171013
DOI: 10.1021/acs.jproteome.3c00756 -
Investigative Ophthalmology & Visual... Dec 2023Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the...
PURPOSE
Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL.
METHODS
Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort.
RESULTS
In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations.
CONCLUSIONS
This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.
Topics: Humans; Vitreous Body; Retinal Neoplasms; Proteomics; Lymphoma, Non-Hodgkin; Sarcoidosis; Proteins; 14-3-3 Proteins
PubMed: 38038618
DOI: 10.1167/iovs.64.15.2 -
Cureus Oct 2023Diabetes mellitus (DM) has become a worldwide problem, endangering the well-being of people. This issue is further aggravated by the increased fatty content in the diet... (Review)
Review
Diabetes mellitus (DM) has become a worldwide problem, endangering the well-being of people. This issue is further aggravated by the increased fatty content in the diet of most of the Indian population. It is a preeminent source of the genesis of morbidity in the citizens of any given continent, including both new-world countries and old ones too. A major stumbling block that diabetes creates in the healthy living of any of its sufferers is a complication called diabetic retinopathy (DR), which, in its most elementary and perspicuous form, refers to damage to the blood vessels in the retina of the human eye that occurs as a result of high serum glucose levels. DR can have many symptoms, including obscure and blurred vision, trouble observing and distinguishing various colors, and eye floaters. One of the most significant reasons for the manifestation of new cases of complete blindness may be attributed to DR. The appearance of lesions in the body's small blood vessels forms the basis of retinopathic detection. The currently accepted approach for the prevention and cure of this ailment targets deterring the microvascular complexities through medicinal agents that are placed directly into the vitreous space, photocoagulation through laser medium (visual perceptivity is balanced), and some other surgeries related to the vitreous chamber. Anti-vascular endothelial growth factor (anti-VEGF) therapy provided to the patient by intravitreal route is, at present, the most crucial process for curing the sufferer of the given illness, as it can result in optical advancement with decreased unfavorable effects.
PubMed: 37954772
DOI: 10.7759/cureus.46842 -
Cureus Nov 2023Diabetic retinopathy (DR) is a significant global health concern, with its prevalence and severity increasing alongside the rising incidence of diabetes. DR is a leading... (Review)
Review
Diabetic retinopathy (DR) is a significant global health concern, with its prevalence and severity increasing alongside the rising incidence of diabetes. DR is a leading cause of vision impairment among working-age adults, resulting in substantial economic and healthcare burdens. This article explores the epidemiology and pathophysiology of DR, highlighting the global variation in its prevalence and the associated systemic risk factors. It delves into the complex relationship between glycemic control, duration of diabetes, and medication use in the context of DR development and progression. The review also discusses current screening methods and their implications, emphasizing the need for efficient and scalable approaches. Furthermore, it investigates the various treatment strategies available for DR, including laser photocoagulation, vitreous body excision, and anti-vascular endothelial growth factor (VEGF) therapy, while underlining their limitations and potential side effects. In conclusion, this article underscores the urgency of developing novel preventive and therapeutic approaches for DR. It highlights the potential role of cytokines and growth factors as treatment targets and emphasizes the importance of glycemic control and management of systemic risk factors in mitigating the impact of this vision-threatening complication of diabetes. The article serves as a comprehensive resource for understanding the challenges posed by DR and the need for innovative strategies to address this growing public health concern.
PubMed: 38143687
DOI: 10.7759/cureus.49211