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Investigative Ophthalmology & Visual... Apr 2024The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration...
PURPOSE
The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration (AMD) at the 10q26 locus, age, sex, AMD status, and/or AMD disease severity, and, therefore, to determine the contribution of systemic and ocular HtrA1 to the AMD disease process.
METHODS
A custom-made sandwich ELISA assay (SCTM ELISA) for detection of the HtrA1 protein was designed and compared with three commercial assays (R&D Systems, MyBiosource 1 and MyBiosource 2) using 65 serum samples. Concentrations of HtrA1 were thereafter determined in serum and vitreous samples collected from 248 individuals and 145 human donor eyes, respectively.
RESULTS
The SCTM ELISA demonstrated high specificity, good recovery, and parallelism within its linear detection range and performed comparably to the R&D Systems assay. In contrast, we were unable to demonstrate the specificity of the two assays from MyBioSource using either recombinant or native HtrA1. Analyses of concentrations obtained using the validated SCTM assay revealed that genetic risk at the 10q26 locus, age, sex, or AMD status are not significantly associated with altered levels of the HtrA1 protein in serum or in vitreous humor (P > 0.05).
CONCLUSIONS
HtrA1 levels in serum and vitreous do not reflect the risk for AMD associated with the 10q26 locus or disease status. Localized alteration in HTRA1 expression in the retinal pigment epithelium, rather than systemic changes in HtrA1, is the most likely driver of elevated risk for developing AMD among individuals with risk variants at the 10q26 locus.
Topics: Aged; Female; Humans; Male; Chromosomes, Human, Pair 10; Enzyme-Linked Immunosorbent Assay; Genetic Predisposition to Disease; High-Temperature Requirement A Serine Peptidase 1; Macular Degeneration; Risk Factors; Sensitivity and Specificity; Serine Endopeptidases; Vitreous Body
PubMed: 38648039
DOI: 10.1167/iovs.65.4.34 -
International Journal of Ophthalmology 2024To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs.
AIM
To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs.
METHODS
The clinical data of 155 patients were retrospectively collected in this study, and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed.
RESULTS
Among the 155 patients (age from 12 to 87 years old, with an average age of 57, 99 males and 56 females) with eye infections (160 eyes: 74 in the left eye, 76 in the right eye and 5 in both eyes, all of which were exogenous), 71 (45.81%) strains were gram-positive bacteria, 23 (14.84%) strains were gram-negative bacteria and 61 (39.35%) strains were fungi. Gram-positive bacteria were highly resistant to penicillin and erythromycin (78.87% and 46.48% respectively), but least resistant to vancomycin at 0. Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole (100% and 95.65% respectively), but least resistant to meropenem at 0. Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences (<0.05) in the resistance of both to cefoxitin, cotrimoxazole, levofloxacin, cefuroxime, ceftriaxone and ceftazidime, and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria. The distribution of bacterial infection strains showed that was the most common strain in the conjunctiva, cornea, aqueous humor or vitreous body and other eye parts. Besides, and were also among the most common strains of conjunctival and corneal infections.
CONCLUSION
Gram-positive bacteria are the dominant bacteria in eye infections, followed by gram-negative bacteria and fungi. Considering the resistance of gram-negative bacteria to multiple drugs, monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.
PubMed: 38638249
DOI: 10.18240/ijo.2024.04.14 -
JAMA Ophthalmology Apr 2024
Topics: Humans; Persistent Hyperplastic Primary Vitreous; Iris Diseases; Pupil Disorders; Ciliary Body; Retinal Diseases
PubMed: 38634925
DOI: 10.1001/jamaophthalmol.2023.4842 -
BMC Ophthalmology Apr 2024To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous...
BACKGROUND
To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits.
METHODS
Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10 mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1 day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis. Three rabbits were euthanized 1 day, 4 weeks, and 12 weeks after treatment, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and hematoxylin-eosin (H&E) staining were used to look for pathological changes in the retina. An enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of vascular endothelial growth factor (VEGF) and some inflammatory cytokines, including interferon inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interlenkin 6 (IL-6) in the vitreous humor. The ascorbic acid (AsA) and total reactive antioxidant potential (TRAP) in the vitreous humor were also measured.
RESULTS
Following Nd:YAG laser vitreolysis, the levels of VEGF, IP-10, MCP-1, IL6, AsA, and TRAP in the vitreous humor did not change substantially (P > 0.05). There were no detectable pathological changes in the retinal tissues, and no apoptotic signal was found.
CONCLUSIONS
Rabbits tolerate Nd:YAG laser vitreolysis without observable impact on retinal tissue or the microenvironment of the vitreous.
Topics: Male; Rabbits; Animals; Vascular Endothelial Growth Factor A; Lasers, Solid-State; Chemokine CXCL10; Vitreous Body; Eye Diseases; Retina; Antioxidants; Ascorbic Acid; Laser Therapy
PubMed: 38627705
DOI: 10.1186/s12886-024-03406-9 -
Journal of Controlled Release :... Jun 2024Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an...
Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an improved understanding of their pharmacokinetics is required, but high-quality in vivo experiments require a large number of animals, raising ethical and economic questions. In order to expedite in vivo kinetic testing of lipid-based systems, we propose a barcode approach that is based on barcoding liposomes with non-endogenous lipids. We developed and evaluated a liquid-chromatography-mass spectrometry method to quantify many liposomes simultaneously in aqueous humor, vitreous, and neural retina at higher than ±20% precision and accuracy. Furthermore, we showed in vivo suitability of the method in pharmacokinetic evaluation of six different liposomes after their simultaneous injection into the rat vitreal cavity. We calculated pharmacokinetic parameters in vitreous and aqueous humor, quantified liposome concentrations in the retina, and quantitated retinal distribution of the liposomes in the rats. Compared to individual injections of the liposome formulations, the barcode-based study design enabled reduction of animal numbers from 72 to 12. We believe that the proposed approach is reliable and will reduce and refine ocular pharmacokinetic experiments with liposomes and other lipid-based systems.
Topics: Animals; Liposomes; Vitreous Body; Aqueous Humor; Lipids; Retina; Male; Rats; Eye; Mass Spectrometry; Chromatography, Liquid; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 38615893
DOI: 10.1016/j.jconrel.2024.04.023 -
Experimental Eye Research Jun 2024The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin,...
The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin, VEGF-C, VEGFR-2 and VEGFR-3. This prospective and interventional study includes 30 patients with AMD which may be dry or wet type and 30 controls for whom vitrectomy and phacoemulsification was indicated due to additional pathologies (epiretinal membrane, macular hole, retinal detachment, and cataract). 0.1-0,2 ml of aqueous humor and 0.5-1 ml of vitreous sample was taken during the operations. Before the operations 1 tube serum was also taken. All the lymphangiogenesis biomarkers in the study are examined by ELISA method. LYVE-1 (p = 0.001) and Podoplanin (p = 0.004) levels in the vitreous for the patient group are found to be significantly lower than the control group. Serum (p = 0.019), vitreous (p = 0.001), aqueous (p < 0.001) levels of VEGF-C for the patient group are significantly higher than the control group. VEGF-C/VEGFR-2 (p < 0.001), VEGF-C/VEGFR-3 (p < 0.001) ratios in the vitreous for the patient group are found to be significantly higher than the control group. Especially in wet AMD patients, LYVE-1 level is significantly lower in the vitreous (p = 0.002) and aqueous (p = 0.002) than the control group. In addition, Podoplanin level is observed as significantly lower in the vitreous (p = 0.014) and serum (p = 0.002) in comparison to control group. In the wet AMD group, VEGF-C level in the vitreous (p < 0.001), aqueous (p < 0.001) and serum (p = 0.001) is higher than the control group. The result of this study indicates a valid relationship between the weakening of lymphangiogenesis and the pathophysiology of AMD, especially for the wet type. It is observed that the levels of receptors that bind VEGF-C (VEGFR-2 and VEGFR-3) do not increase at the same rate as VEGF-C to compensate for the increase in VEGF-C. The absence of an increase in VEGFR-3, which is especially necessary for lymphangiogenesis, also suggests that lymphangiogenesis is weakened or decreased in AMD. In the future interventional studies with larger series, examination of lymphangiogenic biomarkers in inflammatory retinal diseases and glaucoma may reveal unexplored details.
Topics: Humans; Lymphangiogenesis; Male; Female; Biomarkers; Prospective Studies; Aged; Vascular Endothelial Growth Factor Receptor-3; Vascular Endothelial Growth Factor C; Aqueous Humor; Enzyme-Linked Immunosorbent Assay; Vitreous Body; Membrane Glycoproteins; Vesicular Transport Proteins; Vascular Endothelial Growth Factor Receptor-2; Middle Aged; Aged, 80 and over; Macular Degeneration; Wet Macular Degeneration
PubMed: 38615832
DOI: 10.1016/j.exer.2024.109891 -
Forensic Science, Medicine, and... Apr 2024A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of...
A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of the skin in folds around the neck, in the axillae, in the inframammary regions, over the anterior waistline and groin regions and over the dorsal aspects of the feet. These had the typical appearance of acanthosis nigricans. Internal examination revealed aspiration of gastric contents into the airways. Vitreous humour biochemistry showed markedly elevated levels of both glucose (62.9 mmol/L) and β-hydroxybutyrate (13.54 mmol/L). Death was, therefore, due to aspiration pneumonia complicating diabetic ketoacidosis on a background of morbid obesity. The initial indicator of underlying diabetes, in conjunction with obesity had been acanthosis nigricans.
PubMed: 38602653
DOI: 10.1007/s12024-024-00815-6 -
BMC Ophthalmology Apr 2024To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement.
BACKGROUND
To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement.
CASE PRESENTATION
A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates.
CONCLUSIONS
In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.
Topics: Humans; Female; Aged; West Nile Fever; West Nile virus; Eye Infections, Viral; Chorioretinitis; Vitreous Body; Antibodies, Viral
PubMed: 38600458
DOI: 10.1186/s12886-024-03423-8 -
Molecular Biology of the Cell Jun 2024To cause vision-disrupting fibrotic secondary cataract (PCO), lens epithelial cells that survive cataract surgery must migrate to the posterior of the lens capsule and...
To cause vision-disrupting fibrotic secondary cataract (PCO), lens epithelial cells that survive cataract surgery must migrate to the posterior of the lens capsule and differentiate into myofibroblasts. During this process, the cells become exposed to the FGF that diffuses out of the vitreous body. In normal development, such relatively high levels of FGF induce lens epithelial cells to differentiate into lens fiber cells. It has been a mystery as to how lens cells could instead undergo a mutually exclusive cell fate, namely epithelial to myofibroblast transition, in the FGF-rich environment of the posterior capsule. We and others have reported that the ability of TGFβ to induce lens cell fibrosis requires the activity of endogenous ErbBs. We show here that lens fiber-promoting levels of FGF induce desensitization of ErbB1 (EGFR) that involves its phosphorylation on threonine 669 mediated by both ERK and p38 activity. Transinhibition of ErbB1 by FGF is overcome by a time-dependent increase in ErbB1 levels induced by TGFβ, the activation of which is increased after cataract surgery. Our studies provide a rationale for why TGFβ upregulates ErbB1 in lens cells and further support the receptor as a therapeutic target for PCO.
Topics: Humans; Cataract; Epithelial Cells; ErbB Receptors; Fibroblast Growth Factors; Fibrosis; Lens, Crystalline; Myofibroblasts; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Signal Transduction; Transforming Growth Factor beta
PubMed: 38598298
DOI: 10.1091/mbc.E24-01-0040 -
Asia-Pacific Journal of Ophthalmology... 2024
Topics: Humans; Carcinoma, Renal Cell; Endophthalmitis; Kidney Neoplasms; Vitreous Body; Diagnosis, Differential; Male; Eye Neoplasms; Middle Aged; Cytology
PubMed: 38583527
DOI: 10.1016/j.apjo.2024.100055