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Investigative Ophthalmology & Visual... Mar 2023Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles...
PURPOSE
Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics.
METHODS
We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0.
RESULTS
Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment.
CONCLUSIONS
Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.
Topics: Humans; Amides; Carnitine; Macular Degeneration; Niacinamide; Succinates; Vitreous Body
PubMed: 36939720
DOI: 10.1167/iovs.64.3.28 -
International Journal of Biological... May 2024The vitreous is a vital component of the eye, occupying a substantial portion of its volume and maintaining its structure. This study delves into the presence and...
The vitreous is a vital component of the eye, occupying a substantial portion of its volume and maintaining its structure. This study delves into the presence and significance of intrinsically disordered proteins (IDPs) within the vitreous, utilizing a dataset of 1240 vitreous proteins previously discovered in the vitreous proteome by Murthy et al.in five healthy subjects. The results indicate that 26.9 % of vitreous proteins are highly disordered, 68.8 % possess moderate disorder, and only 4.3 % are highly ordered. A complex interaction network among these proteins suggests their biological importance, and approximately 25 % may undergo liquid-liquid phase separation (LLPS). These findings offer new perspectives on the vitreous' molecular composition and behavior, potentially impacting our understanding of eye-related diseases, physiological changes such as vitreous syneresis. Further research is needed to translate these insights into clinical applications, although the intrinsic protein disorder and its association with LLPS appears to play a role in vitreous proteome function.
Topics: Humans; Intrinsically Disordered Proteins; Proteome; Vitreous Body; Eye Proteins
PubMed: 38569991
DOI: 10.1016/j.ijbiomac.2024.131274 -
Journal of Forensic Sciences Sep 2020We present results of our study on the stability of 4-chloromethcathinone (4-CMC) in authentic postmortem peripheral blood and vitreous humor samples. The stability of...
We present results of our study on the stability of 4-chloromethcathinone (4-CMC) in authentic postmortem peripheral blood and vitreous humor samples. The stability of 4-CMC was determined in postmortem blood samples (for a period of 90 days) and vitreous humor (30 days) at three different temperatures: -15°C, +4°C, and + 23°C. The analyses were carried out using ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). In both materials, the lowest 4-CMC stability was demonstrated at room temperature. The blood samples stored in a freezer (-15°C) showed stability for the entire study period (90 days), while in the case of the vitreous humor sample stored at the same temperature the concentration of the substance decreased by 53% after 30 days. The study carried out in authentic postmortem blood and vitreous humor samples confirms the previous reports of 4-CMC instability in biological material. Authors suggest that the biological material should be stored frozen until analyses are carried out as soon as possible after collection of the material.
Topics: Adult; Chromatography, High Pressure Liquid; Drug Stability; Humans; Male; Methylamines; Propiophenones; Psychotropic Drugs; Specimen Handling; Tandem Mass Spectrometry; Temperature; Vitreous Body
PubMed: 32407550
DOI: 10.1111/1556-4029.14454 -
Forensic Science International Apr 2021A more than 500% increase in the number of deaths involving methamphetamine occurred between 2016 and 2018 in Jeddah, Saudi Arabia. As such, this report employed a...
A more than 500% increase in the number of deaths involving methamphetamine occurred between 2016 and 2018 in Jeddah, Saudi Arabia. As such, this report employed a validated liquid chromatography tandem mass spectrometry method to quantify methamphetamine and its metabolites in bodily fluids from 47 postmortem cases in which methamphetamine was involved. The mean age of the deceased was 33 years old (median: 30, range: 16-63), and 94% were male. Methamphetamine was co-ingested with another drug in 32 of the cases (68%); however, the deaths were only due to the combined toxicity of methamphetamine and another drug in 15 of the cases (32%). Of note, 13 of these deaths (28% of all deaths) involved heroin. When methamphetamine was the sole cause of death (32% of the studied cases), the median concentrations of methamphetamine and amphetamine were 527 and 128 ng/mL. When methamphetamine was combined toxicity with another drug, the median concentrations of methamphetamine and amphetamine decreased to 161 and 53 ng/mL. When deaths were unrelated to methamphetamine, the median concentrations of methamphetamine and amphetamine were 130 and 44 ng/mL, respectively. The highest median methamphetamine concentration was found in urine (5281 ng/mL), followed by stomach contents (878 ng/mL), bile (762 ng/mL), vitreous humor (3 ng/mL), and blood (208 ng/mL). Almost 40% of the studied cases involved violence, 61% were accidental, 21% were suicides, 17% were homicides, and 2% were natural deaths. Methamphetamine is highly addictive. Increases in deaths have been seen in various countries. More awareness, education and treatment programs are required to reduce the likelihood of addiction, crimes, suicide, and other fatalities resulting from methamphetamine abuse.
Topics: Accidents; Adolescent; Adult; Age Distribution; Amphetamine-Related Disorders; Bile; Central Nervous System Stimulants; Female; Gastrointestinal Contents; Homicide; Humans; Male; Methamphetamine; Middle Aged; Saudi Arabia; Sex Distribution; Substance Abuse Detection; Suicide, Completed; Vitreous Body; Young Adult
PubMed: 33676238
DOI: 10.1016/j.forsciint.2021.110746 -
Journal of Analytical Toxicology Apr 2021In case of basic biological materials (blood, urine, vitreous humor) being unavailable, bone marrow can be used for toxicological tests. The aim of the study was to...
In case of basic biological materials (blood, urine, vitreous humor) being unavailable, bone marrow can be used for toxicological tests. The aim of the study was to assess the concentration of various xenobiotics in the bone marrow, as well as in the blood and the vitreous humor. The analysis was performed in the biological material originating from the autopsy (n = 120), using the LC-MS method and with liquid/liquid extraction at pH = 9. As many as 46 different xenobiotics were detected in the biological material, strong correlations between the concentration of a given xenobiotic in blood and bone marrow, as well as in the vitreous humor and bone marrow, were noted for most of them, with the exception of diazepam and 7-aminoclonazepam. The obtained results indicate the possibility of using bone marrow to determine the concentration of numerous xenobiotics in the situation of basic biological materials being unavailable, as well as using the results obtained in the future to better understand the pharmacokinetic processes and the effect of postmortem redistribution on medication and drug concentrations in the body of a deceased person.
Topics: Autopsy; Body Fluids; Bone Marrow; Humans; Pharmaceutical Preparations; Postmortem Changes; Vitreous Body
PubMed: 32672811
DOI: 10.1093/jat/bkaa083 -
Experimental Eye Research Apr 2024Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first...
Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first evaluated the circRNA profiles and possible roles in vitreous humor samples of individuals with high myopia by a competitive endogenous RNA (ceRNA) array. Vitreous humor samples were collected from 15 high myopic (5 for ceRNA array, and 10 for qPCR) and 15 control eyes (5 for ceRNA array, and 10 for qPCR) with idiopathic epiretinal membrane (ERM) and macular hole (MH). 486 circRNAs (339 upregulated and 147 downregulated) and 264 mRNAs (202 upregulated and 62 downregulated) were differentially expressed between the high myopia and control groups. The expression of hsa_circ_0033079 (hsa-circDicer1), hsa_circ_0029989 (hsa-circNbea), hsa_circ_0019072 (hsa-circPank1) and hsa_circ_0089716 (hsa-circEhmt1) were validated by qPCR. Pearson analysis and multivariate regression analysis showed positive and significant correlations for axial length with hsa-circNbea and hsa-circPank1. KEGG analysis showed that the target genes of circRNAs were enriched in the mTOR, insulin, cAMP, and VEGF signaling pathways. GO analysis indicated that circRNAs mainly targeted transcription, cytoplasm, and protein binding. CircRNA-associated ceRNA network analysis and PPI network analysis identified several critical genes for myopia. The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, Nras, Itpr1 were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1/miR-145-5p/NRAS and circNbea/miR-204-5p/ITPR1 were identified and may be important in the progression of myopia. Our findings suggest that circRNAs may contribute to the pathogenesis of myopia and may serve as potential biomarkers.
Topics: Humans; Animals; Mice; RNA, Circular; MicroRNAs; Vitreous Body; RNA, Messenger; RNA, Competitive Endogenous; Myopia
PubMed: 38354945
DOI: 10.1016/j.exer.2024.109827 -
Scientific Reports Oct 2023We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement...
We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement method. A micro-optic-fiber pressure sensor was utilized for this purpose. Preliminary experiments with enucleated porcine eyes confirmed the sensor's accuracy in measuring both aqueous and vitreous humor pressure. The main study involved six healthy albino rabbits, where the sensor measured the pressure in the anterior chamber (aIOP) and posterior vitreous-cavity (pIOP). These measurements were compared to aIOP values obtained through rebound tonometry. Additionally, pre- and postoperative pressure comparisons were made after performing a vitrectomy. Results revealed a significant disparity between aqueous and vitreous humor pressures. Prior to vitrectomy, pIOP was 22.8 mmHg, over twice as high as aIOP (11.0 mmHg), but decreased to a similar level following the procedure. Comparison between the sensor measurements and rebound tonometry showed agreement in aIOP values. In conclusion, our study demonstrates that vitreous humor pressure is consistently higher than aqueous humor pressure, reaching the upper limit of normal IOP. Furthermore, vitrectomy effectively reduces pIOP, aligning it with aIOP. These findings contribute valuable insights into intraocular pressure dynamics and have implications for clinical interventions targeting ocular pressure regulation.
Topics: Animals; Swine; Rabbits; Vitreous Body; Intraocular Pressure; Vitrectomy; Tonometry, Ocular; Aqueous Humor
PubMed: 37880357
DOI: 10.1038/s41598-023-45616-z -
Current Eye Research Feb 2023The biomechanical properties of the vitreous humor and replication of these properties to develop substitutes for the vitreous humor have rapidly become topics of...
PURPOSE
The biomechanical properties of the vitreous humor and replication of these properties to develop substitutes for the vitreous humor have rapidly become topics of interest over the last two decades. In particular, the behavior of the vitreous humor as a viscoelastic tissue has been investigated to identify its role in a variety of processes related to biotransport, aging, and age-related pathologies of the vitreoretinal interface.
METHODS
A thorough search and review of peer-reviewed publications discussing the biomechanical properties of the vitreous humor in both human and animal specimens was conducted. Findings on the effects of biomechanics on vitreoretinal pathologies and vitreous biotransport were analyzed and discussed.
RESULTS
The pig and rabbit vitreous have been found to be most mechanically similar to the human vitreous. Age-related liquefaction of the vitreous creates two mechanically unique phases, with an overall effect of softening the vitreous. However, the techniques used to acquire this mechanical data are limited by the testing methods used, and the vitreous humor has been hypothesized to behave differently due in part to its swelling properties. The impact of liquefaction and subsequent detachment of the vitreous humor from the posterior retinal surface is implicated in a variety of tractional pathologies of the retina and macula. Liquefaction also causes significant changes in the biotransport properties of the eye, allowing for significantly faster movement of molecules compared to the healthy vitreous. Recent developments in computational and models of the vitreous humor have helped with understanding its behavior and developing materials capable of replacing it.
CONCLUSIONS
A better understanding of the biomechanical properties of the vitreous humor and how these relate to its structure will potentially aid in improving clinical metrics for vitreous liquefaction, design of biomimetic vitreous substitutes, and predicting pharmacokinetics for intravitreal drug delivery.
Topics: Humans; Animals; Rabbits; Swine; Biomechanical Phenomena; Vitreous Body; Retina; Aging; Eye Diseases
PubMed: 35179421
DOI: 10.1080/02713683.2022.2033271 -
Cells Apr 2021In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of...
In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of novel cytokines involved in the pathogenesis of PDR provides candidate therapeutic targets that may stand alone or work synergistically with current therapies in the management of diabetic retinopathy. Undiluted vitreous humor specimens were collected from 74 patients undergoing vitrectomy for various vitreoretinal disorders. Quantitative immunoassay was performed for a panel of 36 neuroinflammatory cytokines in each specimen and assessed to identify differences between PDR ( = 35) and non-PDR ( = 39) patients. Levels of interleukin-8 (IL-8), IL-15, IL-16, vascular endothelial growth factor (VEGF), VEGF-D, c-reactive protein (CRP), serum amyloid-A (SAA), and intracellular adhesion molecule-1 (ICAM1) were significantly increased in the vitreous of PDR patients compared to non-PDR patients ( < 0.05). We report novel increases in IL-15 and IL-16, in addition to the expected VEGF, in the human vitreous humor of patients with PDR. Additionally, we confirm the elevation of ICAM-1, VCAM-1, SAA, IL-8 and CRP in the vitreous of patients with PDR, which has previously been described.
Topics: C-Reactive Protein; Diabetic Retinopathy; Female; Fibroblast Growth Factor 2; Humans; Intercellular Adhesion Molecule-1; Interleukins; Male; Middle Aged; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A; Vitreous Body
PubMed: 33946446
DOI: 10.3390/cells10051069 -
Current Opinion in Ophthalmology May 2017Visualization remains a critical factor in successful ocular surgery.Here we review new technology that has the potential to allow for safer and more efficient retinal... (Review)
Review
PURPOSE OF REVIEW
Visualization remains a critical factor in successful ocular surgery.Here we review new technology that has the potential to allow for safer and more efficient retinal surgery.
RECENT FINDINGS
Vitreoretinal surgery poses unique visualization challenges such as the need for specialized optical systems and the delicate and microscopic features of retinal structures. Better retinal visualization allows for new approaches to increasingly complex retinal cases. Wide-angle viewing has allowed stereopic visualization of the peripheral retina. Improved lighting systems have shown better safety profiles and can facilitate bimanual techniques. The potential to improve surgical decision making has been shown with intraoperative imaging such as optical coherence tomography.
SUMMARY
Although some of the benefits of these developments have yet to be proven, improved technology for visualization during retinal surgery will hopefully allow for safer and more efficient surgeries.
Topics: Humans; Retina; Tomography, Optical Coherence; Vitreoretinal Surgery; Vitreous Body
PubMed: 28306625
DOI: 10.1097/ICU.0000000000000368