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Haematologica Sep 2022The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma, is challenging. We aimed to investigate the mutational...
The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma, is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as applying ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies. However, the genetic alterations detected in cerebrospinal fluid ctDNA only partially overlapped with those from simultaneously collected AH/VF samples, with much lower allele frequencies. Serial post-treatment AH or VF samples were available for five patients and their changes in ctDNA allele frequency displayed a similar trend as the changes in interleukin-10 levels; an indicator of response to treatment. A cohort of 23 patients with primary central nervous system lymphoma was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of primary central nervous system lymphoma than VRL patients. The objective response rate to ibrutinib treatment was much higher for patients with primary central nervous system lymphoma (64.7%, 11/17) than for those with VRL (14.3%, 1/7). In summary, we provide valuable clinical evidence that AH is a good source of tumor genomic information and can substitute VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring.
Topics: Aqueous Humor; Biomarkers, Tumor; Cell-Free Nucleic Acids; Central Nervous System Neoplasms; Humans; Lymphoma, Non-Hodgkin; Pilot Projects; Retinal Neoplasms; Vitreous Body
PubMed: 35142151
DOI: 10.3324/haematol.2021.279908 -
Frontiers in Endocrinology 2022We sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative...
PURPOSE
We sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative diabetic retinopathy (PDR).
METHODS
Vitreous humor samples were obtained from PDR patients and a control group for this study. Sequencing of small RNAs was conducted to assess the expression profiles of tsRNAs and miRNAs in both groups, which was followed by validation using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatics analyses were conducted to predict the target genes and their potential biological functions and signaling pathways.
RESULTS
A total of 37 tsRNAs and 70 miRNAs with significant differences were screened out from the vitreous humor samples of PDR patients compared to controls. Following validation by RT-qPCR, the target genes of the validated tsRNAs and miRNAs were predicted, and Gene Ontology analysis indicated that the target genes of the tsRNAs were most enriched in the cellular macromolecule metabolic process, cytoplasm, and ion-binding, while those of the miRNAs were most abundant in the regulation of major metabolic process, cytoplasm, and protein-binding. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the target genes of said tsRNAs and miRNAs were most enriched in the adenosine monophosphate-activated protein kinase signaling pathway and Th17 cell differentiation, respectively.
CONCLUSIONS
The present study identified altered tsRNAs and miRNAs in vitreous humor samples of PDR patients, which may play important roles in the pathogenesis of PDR and could be considered potential therapeutic targets in the treatment of PDR.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Gene Ontology; Humans; MicroRNAs; RNA, Transfer; Vitreous Body
PubMed: 35903272
DOI: 10.3389/fendo.2022.913370 -
Molecular Pharmaceutics Feb 2021The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their...
The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their diffusion with single-particle tracking technology and by characterizing their protein coronae with surface plasmon resonance and high-resolution proteomics. Single-particle tracking results indicate that the vitreal mobility of the formulations is dependent on their charge. Anionic and neutral formulations are mobile, whereas larger (>200 nm) neutral particles have restricted diffusion, and cationic particles are immobilized in the vitreous. PEGylation increases the mobility of cationic and larger neutral formulations but does not affect anionic and smaller neutral particles. Convection has a significant role in the pharmacokinetics of nanoparticles, whereas diffusion drives the transport of antibodies. Surface plasmon resonance studies determine that the vitreal corona of anionic formulations is sparse. Proteomics data reveals 76 differentially abundant proteins, whose enrichment is specific to either the hard or the soft corona. PEGylation does not affect protein enrichment. This suggests that protein-specific rather than formulation-specific factors are drivers of protein adsorption on nanoparticles in the vitreous. In summary, our findings contribute to understanding the pharmacokinetics of nanoparticles in the vitreous and help advance the development of nanoparticle-based treatments for eye diseases.
Topics: Adsorption; Animals; Diffusion; Drug Compounding; Humans; Intravitreal Injections; Liposomes; Nanoparticles; Ophthalmic Solutions; Particle Size; Polyethylene Glycols; Protein Corona; Proteomics; Retinal Diseases; Surface Properties; Sus scrofa; Vitreous Body
PubMed: 32584047
DOI: 10.1021/acs.molpharmaceut.0c00411 -
International Journal of Molecular... Jul 2021Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an... (Review)
Review
Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an extensive and complex interactive arena for cytokines in the diabetic eye. In recent decades, there has been significant progress in understanding this environment and its implications in disease pathophysiology. In this review, we investigate the vitreous ecosystem in diabetic retinopathy at the molecular level. Areas of concentration include: the current level of knowledge of growth factors, cytokine and chemokine mediators, and lipid-derived metabolites in the vitreous. We discuss the molecular patho-mechanisms of diabetic retinopathy based upon current vitreous research.
Topics: Aqueous Humor; Chemokines; Cytokines; Diabetes Mellitus; Diabetic Retinopathy; Humans; Intercellular Signaling Peptides and Proteins; Interleukins; Vitreous Body
PubMed: 34281192
DOI: 10.3390/ijms22137142 -
Fa Yi Xue Za Zhi Feb 2023Estimation of postmortem interval (PMI) is one of the important research contents in forensic pathology, and it has always been the focus and hot spot of research work.... (Review)
Review
Estimation of postmortem interval (PMI) is one of the important research contents in forensic pathology, and it has always been the focus and hot spot of research work. In recent years, scholars at home and abroad have made some research progress in estimating PMI by using ocular tissue. After death, the changes of cornea, aqueous humor, iris, lens, vitreous humor and retina all show time sequence change rule highly related to PMI. This paper reviews the research progress of PMI estimation based on the morphological, biochemical, molecular and genetic material changes of different ocular tissue structures after death, and discusses the existing problems and development trends.
Topics: Humans; Postmortem Changes; Time Factors; Autopsy; Vitreous Body; Forensic Pathology
PubMed: 37038856
DOI: 10.12116/j.issn.1004-5619.2021.410602 -
Asia-Pacific Journal of Ophthalmology... Sep 2021The eye, with its distinctive anatomy, not only reflects a wide variety of diseases in life but also undergoes a myriad of post-mortem changes. Consequently, the eye has... (Review)
Review
The eye, with its distinctive anatomy, not only reflects a wide variety of diseases in life but also undergoes a myriad of post-mortem changes. Consequently, the eye has long been an area of interest in forensic science, primarily for the estimation of post-mortem interval and therefore the time of death and also for assistance in ascertaining the cause of death. There has been significant progress in the knowledge of ophthalmic forensic science using new technologies which have allowed further possibilities to arise where understanding of this field can assist the forensic pathologist. This review aims to highlight the current knowledge which exists in this field and also to identify important avenues for further investigation. Post-mortem changes of the eye along with its current applications and challenges will be discussed. These include the important areas of post-mortem iris biometrics, pupil size correlation with post-mortem interval, use of point-of-care technology on vitreous humor, and the use of ophthalmic imaging in pediatric abusive head trauma.
Topics: Autopsy; Child; Forensic Medicine; Humans; Iris; Postmortem Changes; Vitreous Body
PubMed: 34524140
DOI: 10.1097/APO.0000000000000426 -
Forensic Science International Feb 2022This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or...
PURPOSE
This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or positive putrefactive alcohols (PA's) in either medium. Furthermore, it aimed to evaluate the interpretational value of calculated ethanol ratios in relation to EtS and PA results.
METHODS
Blood ethanol positive forensic cases were included; one dataset consisting of 2504 cases with EtS analysed in blood and another dataset with 8001 cases where PA's were analysed.
RESULTS
PA's were found in 24.4% of cases. EtS was negative in 15.3%, 9.4% and 7.4% of cases that were positive for ethanol in blood, urine and vitreous humor, respectively. In EtS negative cases, the concentrations of ethanol in blood, urine and vitreous humor were lower than 0.20 g/kg in 51.3%, 67.4% and 77.8%, respectively. It was 1.0 g/kg or higher in blood in 4.2% of cases. More EtS negative and PA positive cases were seen in central compared to peripheral blood. Ethanol ratios between urine or vitreous humor and blood were significantly lower in both EtS negative and PA positive cases, but large variations were observed.
CONCLUSION
EtS and PA analysis improve the diagnostic accuracy of ethanol in postmortem cases. Postmortem ethanol formation in vitreous humor and urine were both more frequent than expected and we recommend the analysis of ethanol primarily in peripheral blood if available.
Topics: Autopsy; Body Fluids; Ethanol; Humans; Postmortem Changes; Vitreous Body
PubMed: 34952291
DOI: 10.1016/j.forsciint.2021.111152 -
AJNR. American Journal of Neuroradiology Jul 2022There is growing evidence of leakage of gadolinium in an impaired blood-retina barrier. We investigated gadolinium enhancement in different eye compartments and...
BACKGROUND AND PURPOSE
There is growing evidence of leakage of gadolinium in an impaired blood-retina barrier. We investigated gadolinium enhancement in different eye compartments and correlated the enhancement with specific ophthalmologic diseases.
MATERIALS AND METHODS
In a prospective clinical study (ClinicalTrials.gov Identifier: NCT05035251), 95 patients (63 with and 32 without ophthalmologic disease) were examined before and after gadolinium administration (20 and 120 minutes) with heavily T2-weighted FLAIR. The cohort was divided according to the location of pathology into anterior and posterior eye compartment groups. Relative signal intensity increase in the anterior eye chamber, vitreous body with retina, optic nerve sheath, and the Meckel cave was analyzed and correlated with the final clinical diagnosis.
RESULTS
In patients with a disorder in the anterior eye compartment, significant signal intensity increases were found in the central anterior eye chamber ( 20 minutes = .000, 120 minutes = .000), lateral anterior eye chamber ( 20 minutes = .001, 120 minutes = .005), and vitreous body with retina ( 20 minutes = .02) compared with the control group. Patients with pathologies in the posterior eye compartment showed higher signal intensity levels in the central anterior eye compartment ( 20 minutes = .041) and vitreous body with retina ( 120 minutes = .006).
CONCLUSIONS
Increased gadolinium enhancement was found in the central and lateral anterior eye compartments and the vitreous body with retina in patients with anterior eye compartment disorders 20 and 120 minutes after contrast application, suggesting impairment of the blood-aqueous barrier. In patients with a disorder in the posterior eye compartment, pathologic enhancement indicated disruption of the blood-retinal barrier that allows gadolinium to diffuse into the vitreous body with retina from posterior to anterior, opposite to the known physiologic glymphatic pathway.
Topics: Contrast Media; Gadolinium; Glymphatic System; Humans; Magnetic Resonance Imaging; Prospective Studies; Vitreous Body
PubMed: 35772805
DOI: 10.3174/ajnr.A7552 -
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 -
PloS One 2017Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα...
Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines. The study group consisted of 31 consecutive type 2 diabetic patients with PDR who underwent cataract surgery and vitrectomy for vitreous hemorrhage and/or tractional retinal detachment. Undiluted aqueous humor was collected during cataract surgery, and then vitreous fluid was obtained using a 25G vitreous cutter inserted into the mid-vitreous cavity at the beginning of vitrectomy. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα levels in the aqueous humor and vitreous fluid were measured using a beads-array system. Although IL-17A was detected in the aqueous humor of eyes with PDR and the level correlated with IL-17A level in the vitreous fluid, both percent detectable and level of IL-17A in the aqueous humor were significantly lower than those in the vitreous fluid. Vitreous IL-17A level was related significantly to IL-10, IL-22, and TNFα levels in aqueous humor as well as in vitreous fluid, On the other hand, aqueous IL-17A level was not related significantly to aqueous or vitreous levels of IL-10, IL-22 or TNFα level. The present study demonstrated that IL-17A level and detectable rate in the aqueous humor of patients with PDR are markedly lower than those in the vitreous fluid and aqueous IL-17A does not correlate with vitreous levels of other cytokines, and hence should not be used as a surrogate for IL-17A in the vitreous fluid.
Topics: Adult; Aged; Aged, 80 and over; Aqueous Humor; Cytokines; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Th17 Cells; Vitreous Body
PubMed: 28558009
DOI: 10.1371/journal.pone.0178230