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International Ophthalmology Jul 2023To research whether serum vascular endothelial growth factor (VEGF) levels could be used to evaluate diabetic retinopathy (DR) progression and to compare vitreous VEGF...
PURPOSE
To research whether serum vascular endothelial growth factor (VEGF) levels could be used to evaluate diabetic retinopathy (DR) progression and to compare vitreous VEGF levels after injections of intravitreal bevacizumab (IVB), ranibizumab (IVR), and triamcinolone acetonide (IVTA) in proliferative diabetic retinopathy (PDR).
METHODS
We enrolled a total of 91 eyes of 89 subjects (70 eyes of 68 diabetics and 21 eyes of 21 non-diabetic controls). The diabetic subjects were divided into three groups as PDR (n = 28), non-proliferative diabetic retinopathy (n = 20), and no-DR (n = 20). Eyes with PDR (n = 31) were injected with IVB (n = 7), IVR (n = 10), or IVTA (n = 6) 3 days before vitrectomy, and eight eyes did not receive an injection. Serum and vitreous samples were collected before vitrectomy and analyzed using ELISA.
RESULTS
We found the severity of retinopathy was not correlated with serum VEGF levels (P = .919, ρ = -0.011). Compared with the controls, vitreous VEGF was higher in the PDR (P < .001), whereas serum VEGF did not differ (P = .99). The controls had lower vitreous VEGF than the IVB, IVR, and no-injection subgroups (P = .01, P < .001, and P = .04, respectively). Vitreous VEGF was similar among the injected and no-injection subgroups (P = .17).
CONCLUSIONS
Serum VEGF levels may not directly reflect retinopathy progression. Neither IVB, IVR nor IVTA could eliminate vitreous VEGF levels within 3 days before vitrectomy.
Topics: Humans; Vascular Endothelial Growth Factor A; Diabetic Retinopathy; Vitreous Body; Bevacizumab; Ranibizumab; Vitrectomy; Enzyme-Linked Immunosorbent Assay; Diabetes Mellitus
PubMed: 36580154
DOI: 10.1007/s10792-022-02620-y -
Forensic Science, Medicine, and... Sep 2023Correctly estimating the post-mortem interval (PMI) is essential in forensic practice. In recent decades, the measurement of vitreous humor analyte concentrations -...
Correctly estimating the post-mortem interval (PMI) is essential in forensic practice. In recent decades, the measurement of vitreous humor analyte concentrations - especially of hypoxanthine and potassium - and their correlation with the PMI have returned good results. However, calculating the PMI from the data collected can be quite complex. The present paper describes a web resource ( http://modestya.usc.es:3838/Forensic/ ) that simplifies the procedure. The PMI is determined (with its 95% confidence interval) in a rapid, easy, and reliable manner based on the use of mathematical models, the biochemistry of the vitreous humor, and physical variables such as the ambient temperature, the rectal temperature, and bodyweight. The application is entirely free to use.
Topics: Humans; Postmortem Changes; Autopsy; Forensic Medicine; Models, Theoretical; Vitreous Body; Potassium
PubMed: 36199004
DOI: 10.1007/s12024-022-00537-7 -
Forensic Toxicology Apr 2024Τhe aim of the present study was to investigate the use of vitreous humor as an alternative biological material in forensic toxicology for the determination of...
PURPOSE
Τhe aim of the present study was to investigate the use of vitreous humor as an alternative biological material in forensic toxicology for the determination of quetiapine, 7-hydroxy-quetiapine, and nor-quetiapine. The distribution of these substances in vitreous humor was studied by determining and correlating their concentrations in vitreous humor with the respective concentrations in blood.
METHODS
During this study, a method for the determination of these substances was developed, validated and applied to postmortem samples obtained from 16 relative forensic cases. The sample preparation procedure included the isolation of the analytes from vitreous humor and blood samples using solid-phase extraction, with Bond Elut LRC C18 columns followed by derivatization with BSTFA with 1% TMCS prior to GC/MS analysis.
RESULTS
The developed method is characterized by a dynamic range of 10.0-1000.0 ng/mL (R ≥ 0.991) for the three substances, with a limit of detection and quantification of 3.0 and 10.0 ng/mL, respectively. Accuracy and precision were below 8.09% and 8.99%, respectively, for both biological materials, while absolute recovery for the three substances was greater than 81%. According to the results, quetiapine, 7-hydroxy-quetiapine, and nor-quetiapine are easily distributed in vitreous humor.
CONCLUSION
The results of the study indicate the usefulness of vitreous humor in toxicological analysis for the determination of these substances, especially when the traditional biological materials are not available. The levels of quetiapine and its metabolites in vitreous humor as well as the vitreous humor to blood concentration ratios can provide important information for a more thorough toxicological investigation of forensic cases.
PubMed: 38615314
DOI: 10.1007/s11419-024-00687-z -
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 -
Experimental Eye Research Sep 2023Proliferative diabetic retinopathy (PDR) adversely affects visual function. Extracellular matrix proteins (ECM) contribute significantly to the development of PDR. A...
Proliferative diabetic retinopathy (PDR) adversely affects visual function. Extracellular matrix proteins (ECM) contribute significantly to the development of PDR. A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 (ADAMTS5) is a member of ECM proteins. ADAMTS5 participates in angiogenesis and inflammation in diverse diseases. However, the role of ADAMTS5 in PDR remains elusive. Multiplex beam array technology was used to analyze vitreous humor of PDR patients and normal people. ELISA and Western blot were used to detect the expression of ADAMTS5, PEDF and autophagy related factors. Immunofluorescence assay was used to mark the expression and localization of ADAMTS5 and PEDF. The neovascularization was detected by tube formation test. Our results revealed that ADAMTS5 expression was increased in the vitreous humor of PDR patients and oxygen-induced retinopathy (OIR) mice retinas. Inhibiting ADAMTS5 alleviated pathological angiogenesis and upregulated PEDF expression in the OIR mice. In addition, ADAMTS5 inhibited PEDF secretion in ARPE-19 cells in vitro studies, thereby inhibiting the migration of HMEC-1. Mechanically, ADAMTS5 promoted the autophagic degradation of PEDF. Collectively, inhibition of ADAMTS5 during OIR suppresses pathological angiogenesis. Our study provides a new approach for resolving pathological angiogenesis in PDR.
Topics: Animals; Mice; Autophagy; Diabetes Mellitus; Diabetic Retinopathy; Eye Proteins; Neovascularization, Pathologic; Retinal Diseases; Retinal Neovascularization; Serpins
PubMed: 37490993
DOI: 10.1016/j.exer.2023.109597 -
Advanced Drug Delivery Reviews Sep 2023Owing to the variety and complexity of ocular diseases and the natural ocular barriers, drug therapy for ocular diseases has significant limitations, such as poor drug... (Review)
Review
Owing to the variety and complexity of ocular diseases and the natural ocular barriers, drug therapy for ocular diseases has significant limitations, such as poor drug targeting to the site of the disease, poor drug penetration, and short drug retention time in the vitreous body. With the development of biotechnology, biomedical materials have reached the "smart" stage. To date, despite their inability to overcome all the aforementioned drawbacks, a variety of smart materials have been widely tested to treat various ocular diseases. This review analyses the most recent developments in multiple smart materials (inorganic particles, polymeric particles, lipid-based particles, hydrogels, and devices) to treat common ocular diseases and discusses the future directions and perspectives regarding clinical translation issues. This review can help researchers rationally design more smart materials for specific ocular applications.
Topics: Humans; Drug Delivery Systems; Biocompatible Materials; Polymers; Pharmaceutical Preparations
PubMed: 37451500
DOI: 10.1016/j.addr.2023.115006 -
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