Structural, blood flow and functional changes in the macular area and the expression of aqueous humor factors in myopia.

Objective: To compare the macular area parameters and aqueous humor factors between myopia and emmetropia. Methods: Convenience sampling was used to select patients who visited the Changzhi Aier Eye Hospital's department of ophthalmology from December 2018 to December 2022 as the study participants. They were divided into three groups according to whether they were diagnosed as mild myopia myopic, highly myopic or not as follows: the mild myopia group (60 cases, 108 eyes), the high myopia group (46 cases, 78 eyes) and the healthy emmetropia group (40 cases, 65 eyes). The differences in the macular integrity (MI) assessment, optical coherence tomography and optical coherence tomography angiography parameters and aqueous humor factors were compared between the three groups. Results: AL in high myopia group was the highest, and that in emmetropia group was the lowest. The BCVA of mild myopia group was the highest. The RS in the high myopia group were significantly lowest in the three groups (26.42 ± 1.04 vs. 28.34 ± 0.76 vs. 31.92 ± 0.77) (F = 5.374, p = 0.013). The 63% BCEA, 95% BCEA and MI in the high myopia group were significantly highest (p < 0.05). The mean RPE thickness, mean CT and mean RT in the high myopia group were lowest (p < 0.05). The blood flow density were lowest in the superficial fovea, paracentral fovea and different subdivisions of the paracentral fovea in the high myopia group (p < 0.05). The VEGF concentration in the aqueous humor of the high myopia group was lowest (25.62 ± 17.43 vs. 32.45 ± 24.67 vs. 64.37 ± 21.14) (F = 9.237, p < 0.001). The MMP-2 concentration was highest (483 ± 201.48 vs. 410 ± 142.37 vs. 386 ± 154.34) (F = 5.542, p = 0.018). The VEGF concentration in the aqueous humor factor was negatively correlated with the AL in the myopia group (r = -0.438, p = 0.002), the MMP-2 concentration was positively correlated with the AL (r = 0.484, p = 0.010). Conclusion: Patients with high myopia showed decreased retinal light sensitivity, fixation stability, superficial blood flow density and retinal thickness compared with people with emmetropia. A decreased VEGF concentration and increased MMP-2 concentration in the aqueous humor factor have potential associations with the development of high myopia.

Lipid profile in the aqueous humor of patients with myopia.

We examined the lipid profiles in the aqueous humor (AH) of myopic patients to identify differences and investigate the relationships among dissertating lipids. Additionally, we assessed spherical equivalents and axial lengths to explore the pathogenesis of myopia. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to qualitatively and quantitatively analyze the lipid composition of samples from myopic patients with axial lengths <26 mm (Group A) and >28 mm (Group B). Differences in lipid profiles between the two groups were determined using univariate and multivariate analyses. Receiver operator characteristic (ROC) curves were used to identify discriminating lipids. Spearman correlation analysis explored the associations between lipid concentrations and biometric parameters. Three hundred and nine lipids across 21 lipid classes have been identified in this study. Five lipids showed significant differences between Group B and Group A (VIP > 1, P < 0.05): BMP (20:3/22:3), PG (22:1/24:0), PS (14:1/22:4), TG (44:2)_FA18:2, and TG (55:3)_FA18:1. The area under the curve (AUC) for these lipids was >0.75. Notably, the concentrations of BMP (20:3/22:3), PS (14:1/22:4), and TG (55:3)_FA18:1 were correlated with spherical equivalents, while BMP (20:3/22:3) and PS (14:1/22:4) correlated with axial lengths. Our study identified five differential lipids in myopic patients, with three showing significant correlations with the degree of myopia. These findings enhance our understanding of myopia pathogenesis through lipidomic alterations, emphasizing changes in cell membrane composition and function, energy metabolism and storage, and pathways involving inflammation, peroxisome proliferator-activated receptors (PPAR), and metabolic processes related to phosphatidylserine, phosphatidylglycerol, triglycerides, polyunsaturated fatty acids, and cholesterol.

Aqueous humor cytokine levels in patients with subretinal fibrosis in neovascular age-related macular degeneration.

PURPOSE: To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity. METHODS: The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), platelet-derived growth factor-BB (PDGF-BB). RESULTS: Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P < 0.05), and VEGF, bFGF and TGF-α levels were significantly higher in SRFi patients than controls (all P < 0.05). No significant differences in 4 cytokine levels were observed between nAMD and SRFi patients in aqueous humor. We also identified a positive correlation between the aqueous humor levels of IL-6 and VEGF in the SRFi group, while bFGF and TGF-α in the nAMD group. Moreover, VEGF levels were strongly related to BCVA, and bFGF levels were positively related to the maximum thickness of subretinal hyperreflective material (SHRM) in fibrosis due to nAMD. CONCLUSION: VEGF and bFGF levels in aqueous humor were elevated in macular neovascularization with and without subretinal fibrosis. TGF-α levels exclusively differed in neovascular AMD with fibrosis. Cytokines are distributed differently and play a synergistic role in different stages (angiogenesis and fibrogenesis) of nAMD. The bFGF levels could predict the negative prognosis in fibrosis due to nAMD.

Expression of Matrix Metalloproteinase-3 in the Aqueous Humor of Patients with Posner-Schlossman Syndrome.

PURPOSE: To explore the expression of matrix metalloproteinase-3 (MMP-3) in the aqueous humor of patients with Posner-Schlossman syndrome (PSS), and the association between MMP-3 and PSS. METHODS: Peripheral blood and aqueous humor were routinely collected from 29 patients with PSS (PSS group) and 30 patients with age-related-cataract (ARC) (control group). The content of MMP-3 in serum and aqueous humor was measured by immunoturbidimetry. The correlation between MMP-3 and ophthalmic examination results were verified by Spearman's correlation analysis. RESULTS: The MMP-3 level in the aqueous humor of the PSS group was (25.86 ± 13.4)ng/ml, significantly higher than that in the control group (3.9 ± 2.7)ng/ml(p < 0.001), while there was no significant difference in serum MMP-3 level between the two groups (p = 0.125). The endothelial cell density (ECD) in the aqueous humor of the PSS group was (2078 ± 440) cell/mm2, intraocular pressure (IOP) in the aqueous humor of the PSS group was (33 ± 12) mmHg. The correlation analysis of aqueous humor MMP-3 and various ophthalmic examination results showed that aqueous humor MMP-3 had a moderate correlation with IOP and the difference in ECD between the affected eye and the fellow eye. CONCLUSIONS: MMP-3 level is elevated in the aqueous humor of PSS patients, and it may play an important role in the pathogenesis of PSS.

Trends and hot spots in research related to aqueous humor from 2014 to 2023: A bibliometric analysis.

Purpose: To analyze publication trends and investigate research hotspots of aqueous humor (AH) studies. Methods: A bibliometric study was conducted based on the Web of Science Core Collection (WOSCC). VOSviewer v. 1.6.18 was utilized to create a knowledge map visualizing the number of annual publications, the distribution of countries, international collaborations, author productivity, source journals and keywords in the field. Results: A grand total of 4020 peer-reviewed papers concerning AH were retrieved from 2014 to 2023. The United States of America secured the top position among the most published countries and Duke University emerged as the most active institution. Stamer, WD contributed the most papers in this area. Investigative Ophthalmology & Visual Science was the most prolific journal in AH research. Retrieved publications mainly concentrated on the correlation between AH as a biomarker carrier and different ocular disorders. Six clusters were formed based on the keywords: (1) the diagnosis of endophthalmitis and AH pharmacokinetics; (2) the association of AH with pathogenesis and prognosis of glaucoma; (3) diagnosis and treatment of AH associated with uveitis; (4) the relationship between AH and refractive diseases of the eye; (5) the association of AH with mechanism and biomarkers of ocular tumorigenesis; (6) the indicators of AH associated with fundus disease. Conclusions: This study unveiled present patterns of global collaboration, emerging frontiers, fundamental knowledge, research hotspots and current trends in AH.

Netarsudil 0.02% Alters Episcleral Venous Flowrates: A Clinical Trial Using Erythrocyte-Mediated Angiography.

Objective: To characterize the effect of netarsudil 0.02% on episcleral blood flow in treatment-naive glaucoma suspect or ocular hypertension subjects. Design: Prospective, unmasked, single-arm cohort study. Participants: Ten treatment-naive patients with a diagnosis of glaucoma suspect or ocular hypertension. Methods: Erythrocyte-mediated angiography (EMA) was used to measure episcleral erythrocyte velocity, vessel diameter, and blood flow at baseline before treatment, 1 hour after drop instillation (T1), 1 to 2 weeks after daily netarsudil 0.02% drop use (T2), and 1 hour after drop instillation at the 1-to-2-week time point (T3). Intraocular pressure (IOP) and blood pressure were measured at each visit. Main Outcome Measures: Change in episcleral venous erythrocyte velocity, diameter, and blood flow between time points analyzed using generalized estimating equation models. Results: Of the 18 eligible study eyes of 10 enrolled treatment-naive subjects, baseline IOP was 16.8 ± 3.6 mmHg (mean ± standard deviation), which significantly decreased to 13.9 ± 4.2 mmHg at T1, 12.6 ± 4.1 mmHg at T2, and 11.8 ± 4.7 mmHg at T3 (P < 0.05 at each time point compared with baseline). Episcleral vessels averaged 61.3 ± 5.3 µm in diameter at baseline which increased significantly at all posttreatment time points (78.0 ± 6.6, 74.0 ± 5.2, 76.9 ± 6.9 µm, respectively; mean ± standard deviation, P < 0.05 for each time point). Episcleral venous flowrates were 0.40 ± 0.22 uL/minute (mean ± standard deviation) at baseline, which increased significantly to 0.69 ± 0.45 uL/min at T1 (P = 0.01), did not significantly differ at T2 (0.38 ± 0.30 uL/minute), and increased significantly to 0.54 ± 0.32 uL/minute at T3 (P < 0.05 compared with baseline and T2). Conclusions: Netarsudil causes episcleral venous dilation at all time points and resulting increases in episcleral venous flowrates 1 hour after drop instillation. Increased episcleral venous flow, associated with decreased episcleral venous pressure, may result in lowered IOP. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Green and sensitive detection of olopatadine in aqueous humor using a signal-on fluorimetric approach: GREEnness assessment.

Olopatadine (OLP) is widely utilized as an effective antihistaminic drug for alleviating ocular itching associated with allergic conjunctivitis. With its frequent usage in pharmacies, there arises a pressing need for a cost-effective, easily implementable, environmentally sustainable detection method with high sensitivity. This study presents a novel signal-on fluorimetric method for detecting OLP in both its pure form and aqueous humor. The proposed approach depends on enhancing the weak intrinsic fluorescence emission of OLP, achieving a remarkable increase of up to 680% compared to its intrinsic fluorescence. This enhancement is achieved by forming micelles around protonated OLP using an acetate buffer (pH 3.6) and incorporating a solution of sodium dodecyl sulfate (SDS) surfactant. A strong correlation (R = 0.9996) is observed between the concentration of OLP and fluorescence intensities ranging from 1.0 to 100.0 ng mL-1 with a limit of detection of 0.22 ng mL-1. This described method is successfully employed for quantifying OLP in both its powder form and pharmaceutical eye drops. Furthermore, it demonstrates robust performance in determining OLP in artificial aqueous humor with a percentage recovery of 99.05 ± 1.51, with minimal interference from matrix interferents. Moreover, the greenness of the described method was evaluated.

Single-cell somatic copy number alteration profiling of vitreous humor seeds in retinoblastoma.

BACKGROUND: Heterogeneity can impact biomarker identification. Thus, we investigated the somatic copy number alterations (SCNAs) of individual tumor cells in the vitreous humor of a retinoblastoma patient using single-cell whole-genome profiling and explored the genomic concordance among vitreous and aqueous humor, vitreous seeds, and tumor. METHODS: Aqueous humor (AH), vitreous humor (VH), and tumor biopsy were obtained from an enucleated globe with retinoblastoma and vitreous seeding. Micromanipulation was used to manually isolate 39 live single tumor cells from vitreous seeds harvested from the VH. The SCNA profiles of these individual cells were generated via whole-genome sequencing and analyzed alongside profiles from the tumor mass and cell-free DNA (cfDNA) from AH and VH. RESULTS: Heatmap of VH single-cell SCNA profiles demonstrates heterogeneity among individual vitreous seeds with one clearly dominant subclone (23 of 37 cells). The SCNA profiles from the cells in this subclone demonstrate an average concordance of 98% with cfDNA profiles from acellular AH and VH and with the tumor profile. CONCLUSIONS: Our findings reveal some heterogeneity among single-cell SCNA profiles in individual VH seeds. Despite this heterogeneity, the dominant vitreous subclone exhibits extremely (>98%) high concordance with the SCNA profile from tumor and AH, suggesting AH cfDNA is representative of the dominant genomic subclone. This may facilitate tumoral biomarker identification via the AH. This preliminary work supports the potential of applying single-cell technology to VH seeds in retinoblastoma as a platform to study tumor subclones, which may provide insight into the genomic complexity of disease.

Silk fibroin/vitreous humor hydrogel scaffold modified by a carbodiimide crosslinker for wound healing.

Natural-derived biomaterials can be used as substrates for the growth, proliferation, and differentiation of cells. In this study, bovine vitreous humor as a biological material was cross-linked to silk fibroin with different concentration ratios to design a suitable substrate for corneal tissue regeneration. The cross-linked samples were evaluated with different analyses such as structural, physical (optical, swelling, and degradation), mechanical, and biological (viability, cell adhesion) assays. The results showed that all samples had excellent transparency, especially those with higher silk fibroin content. Increasing the ratio of vitreous humor to silk fibroin decreased mechanical strength and increased swelling and degradation, respectively. There was no significant difference in the toxicity of the samples, and with the increase in vitreous humor ratio, adhesion and cell proliferation increased. Generally, silk fibroin with vitreous humor can provide desirable characteristics as a transparent film for corneal wound healing.

The interplay between patients and healthcare professionals in a cross-sectoral setting in connection with the treatment and care of patients with diabetic foot ulcers: a realistic evaluation.

BACKGROUND: Diabetes-related lower extremity complications such as diabetic foot ulcer (DFU) are a global disability burden. Treatment and care for patients with DFU call for a multisectoral approach that incorporates interdisciplinary care pathways. We aimed to explore the interplay between patients with DFU and healthcare professionals in cross-sectoral settings that address treatment and care and to determine "what works, for whom, and under what circumstances". METHOD: The study was designed as a realistic evaluation. The data were generated from September 2022 to March 2023 and drew upon approximately 60 h of participant observation of 14 patients during the treatment and care of DFUs in their homes (primary care) and/or at outpatient clinics (wound specialist clinics in a hospital setting) in a Danish cross-sectoral setting. The Standards for Reporting Qualitative Research (SRQR) were applied in this study. RESULTS: We identified three illuminating themes that described the interplay between patients with DFU and related healthcare professionals representing both primary and secondary health care systems: (1) humour is a relationship-enhancing element between nurses and patients; (2) support from patients' coping strategies promotes patient-centeredness and collaboration; and (3) patients and professionals occupy unnegotiated identity roles. CONCLUSION: Our study led to a refined programme theory developed through the realistic evaluation process that allows us to propose an answer to the problem of "what works, for whom, and under what circumstances". The interplay between patients with DFU and healthcare professionals in a cross-sectoral setting for treatment and care is characterised by the use of humour as a relation-enhancing element and by improving support for patient coping strategies, which encourages healthcare professionals to promote health literacy. Future research should examine strategies for negotiating identity roles between patients with DFU and healthcare professionals to enhance collaboration, patient health literacy, and health promotion in cross-sectoral healthcare settings.

Analysis of Sphingosine and Sphinganine from the Aqueous Humor for Signaling Studies Using Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry.

Sphingolipids, including sphingosine and sphinganine, are one of the major classes of lipids. They serve as constituents of cell membranes and lipid rafts and aid in the performance of cell-cell communication and adhesion. Abnormal levels of sphingolipids in the aqueous humor can indicate impaired sphingolipid metabolism and associated ocular pathologies. Sphingolipids can be extracted from the aqueous humor by the methyl-tert-butyl ether (MTBE) lipid extraction method and subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). This chapter describes a modified protocol for an MTBE lipid extraction from the aqueous humor, followed by analysis with ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS).

Proteomics Analyses of Small Extracellular Vesicles of Aqueous Humor: Identification and Validation of GAS6 and SPP1 as Glaucoma Markers.

Cataracts and glaucoma account for a high percentage of vision loss and blindness worldwide. Small extracellular vesicles (sEVs) are released into different body fluids, including the eye's aqueous humor. Information about their proteome content and characterization in ocular pathologies is not yet well established. In this study, aqueous humor sEVs from healthy individuals, cataracts, and glaucoma patients were studied, and their specific protein profiles were characterized. Moreover, the potential of identified proteins as diagnostic glaucoma biomarkers was evaluated. The protein content of sEVs from patients' aqueous humor with cataracts and glaucoma compared to healthy individuals was analyzed by quantitative proteomics. Validation was performed by western blot (WB) and ELISA. A total of 828 peptides and 192 proteins were identified and quantified. After data analysis with the R program, 8 significantly dysregulated proteins from aqueous humor sEVs in cataracts and 16 in glaucoma showed an expression ratio ≥ 1.5. By WB and ELISA using directly aqueous humor samples, the dysregulation of 9 proteins was mostly confirmed. Importantly, GAS6 and SPP1 showed high diagnostic ability of glaucoma, which in combination allowed for discriminating glaucoma patients from control individuals with an area under the curve of 76.1% and a sensitivity of 65.6% and a specificity of 87.7%.

The mediating effects of moral disengagement and aggressive humor style: Dark Triad traits and schadenfreude.

Background: While schadenfreude is commonly experienced in interpersonal relationships, it is generally considered immoral. Although previous research has explored the factors relating to schadenfreude, including certain personality traits, moral disengagement, and humor styles, our understanding of these factors remains limited. The present study examined the mediating effects of moral disengagement and aggressive humor style in the relationship between the Dark Triad traits and schadenfreude. Methods: In this study, a sample of 693 Iranian students (69.4% female), was recruited using a convenient sampling method, consisting of 330 undergraduate, 230 graduate, and 133 Ph.D. students. The trait schadenfreude scale, the short Dark Triad, the moral disengagement scale, and the aggressive humor style scale were measured through an online survey. Results: The study found that Machiavellianism, narcissism, and psychopathy were positively related to schadenfreude, aggressive humor style, and moral disengagement. Additionally, aggressive humor style and moral disengagement mediated the relationship between Machiavellianism, narcissism, and psychopathy with schadenfreude. Conclusion: This study provides insights into the complex relationships between Dark Triad traits, moral disengagement, aggressive humor style, and schadenfreude. The findings suggest that individuals with higher levels of Dark Triad traits may be more likely to experience pleasure from others' misfortunes. Furthermore, the study highlights the importance of moral disengagement and aggressive humor style as potential mechanisms underlying the relationship between Dark Triad traits and schadenfreude. Further research should be done to explore the motivational factors influencing schadenfreude in specific settings, thereby elucidating these connections.

Endothelin-1 Plasma and Aqueous Humor Levels in Different Types of Glaucoma: A Systematic Review and Meta-Analysis.

Background and Objectives: Several studies suggest the complex relationship between Endothelin-1 (ET-1) levels with various types of glaucoma. This systematic review and meta-analysis explore ET-1 levels in plasma and aqueous humor among different types of glaucoma. Materials and Methods: A literature search (PubMed, ScienceDirect, Cochrane Library) was made up to April 2024 (PROSPERO: CRD42023430471). The results were synthesized according to PRISMA Guidelines. Results were presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 2597 subjects (1513 patients with glaucoma vs. 1084 healthy controls) from 23 studies were included in a meta-analysis. Notably, patients with glaucoma reported significantly higher plasma levels of ET-1 compared to controls (SMD: 1.21, 95% CI: 0.59-1.82, p < 0.001). Particularly, plasma ET-1 levels were higher in primary open-angle glaucoma (POAG) (SMD: 0.87, 95% CI: 0.09-1.65, p < 0.05), normal-tension glaucoma (SMD: 0.86, 95% CI: 0.27-1.46, p = 0.05), and angle-closure glaucoma patients (SMD: 1.03, 95% CI: 0.43-1.63, p < 0.001) compared to healthy controls. Moreover, ET-1 aqueous humor levels were significantly higher in patients with glaucoma compared to controls (SMD: 1.60, 95% CI: 1.04-2.15, p < 0.001). In particular, aqueous humor levels were higher in POAG patients (SMD: 2.03 95% CI: 1.00-3.14, p < 0.001), and pseudoexfoliative glaucoma patients (SMD: 2.03, 95% CI: 1.00-3.07, p < 0.001) compared to controls. Conclusions: This meta-analysis indicates that elevated levels of ET-1 plasma and aqueous humor are significantly associated with different types of glaucoma. The pathogenesis of ET-1-related mechanisms may vary across different glaucoma types, indicating that possible therapeutic approaches targeting ET-1 pathways should be tailored to each specific glaucoma type.

Hearing laughter: a prescription for anxiety relief.

Anxiety can have adverse effects on cognition such as impairing test performance or restricting working memory. One way of reducing anxiety is through humor, and the present research investigated if the perception of laughter, which is often seen as a reaction to humor, could impact self-reported anxiety. Participants completed the STAI battery containing subscales for both state and trait anxiety before and after one of three manipulations: a laughter sounds rating task, a neutral sounds rating task, or a working memory span task. Results showed that perceiving laughter decreased both state and trait anxiety, taking a working memory test increased state anxiety, and perceiving neutral sounds had no effect on either type of anxiety. These findings are interpreted as evidence that the positive emotions induced by hearing laughter help to regulate anxiety by undoing arousal, even when negative emotions are not present.

Humor in professional coaching: a literature review and research agenda.

Introduction: Extensive research has explored the incorporation of humor in therapy, revealing its potential positive effects on clients' mental well-being and personal growth. However, limited research exists on how coaching could benefit from humor as an intervention and how its utilization impacts the interaction processes and outcomes for both the coachee and coach. Therefore, our research focuses on the use and effects of spontaneous humor within professional dialogues. This paper aims to extract insights from academic literature on humor in adjacent fields and apply these insights to the context of coaching. Methods: This paper offers implications for coaching theory and practice, alongside a proposed research agenda. The initial phase involves analyzing reviews on humor in professional contexts, and coaching. Secondly, following the PRISMA guidelines for review, we identified 13 empirical studies, which address the role of humor in counseling, psychotherapy, and mentoring. Results and discussion: Our findings suggest that humor serves as a valuable tool for establishing and deepening the working alliance, fostering adaptive coping mechanisms in clients, and enhancing the cognitive and behavioral process. Moreover, humor is shown to be advantageous for professionals in navigating challenging client relationships. These findings hold significance for the realm of coaching practice as well. In light of these insights, we propose the integration of humor use in education toolkits for coaching professionals.

Ascorbic acid export from human donor lenses: Is the lens a source of ascorbic acid in the ocular humors?

In previous work, we have shown that the lens acts a reservoir of the antioxidant glutathione (GSH), capable of exporting this antioxidant into the ocular humors and potentially protecting the tissues of the eye that interface with these humors from oxidative stress. In this study, we have extended this work by examining whether the lens acts as a source of ascorbic acid (AsA) to maintain the high levels of AsA known to be present in the ocular humors either by the direct export of AsA into the humors and/or by functioning as a recycling site for AsA, via the direct uptake of oxidised ascorbate (DHA) from the humors, its regeneration to AsA in the lens and then its subsequent export back into the humors. To test this, human lenses of varying ages were cultured for 1 h under hypoxic conditions and AsA/DHA levels measured in the media and in the lens. Human lenses were also cultured in compartmentalised chambers to determine whether efflux of AsA/DHA occurs at the anterior or posterior surface. Immunohistochemistry was performed on human donor lenses and sections labelled with antibodies against GLUT1, a putative DHA uptake transporter. Vitreous humor was collected from patients undergoing vitrectomy who either had a natural clear lens, an artificial intraocular implant (IOL) or a cataractous lens, and AsA/DHA and GSH and oxidised GSH (GSSG) measured. We found that cultured human donor lenses released both AsA and DHA into the media. Culturing of lenses in a compartmentalised chamber revealed that AsA and DHA efflux occurs at both surfaces, with relatively equal amounts of AsA and DHA released from each surface. The posterior surface of the lens was shown to express the GLUT1 transporter. Analysis of vitreous samples from patients undergoing vitrectomy revealed that vitreous GSH and AsA levels were similar between the natural lens group, IOL and cataractous lens group. Taken together, while human donor lenses were shown to export AsA and DHA into the surrounding media, the amount of AsA and DHA released from donor lenses was low and not sufficient to sustain the high levels of total AsA normally present in the humors. This suggests that although the lens is not the main source for maintaining high levels of AsA in the ocular humors, the lens may help to support local AsA levels close to the lens.

Development and characterization of a chronic high intraocular pressure model in New Zealand white rabbits for glaucoma research.

Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges. In this study, we developed a rabbit glaucoma model that does not require experimental disease induction. Rabbits were chosen as the model because their eyeballs are similar in size to those of humans, and they are easy to breed. By crossing rabbit strains with inherited glaucoma, as indicated by obvious buphthalmos, we produced a strain that exhibits ocular hypertension. The IOP of the Ocular Hypertension (OH) rabbits was significantly higher than that of the wild type (WT; normal New Zealand white rabbits) from the age of 3 weeks to at least 22 weeks. The significantly larger corneal diameter of the OH rabbits indicated ocular enlargement, whereas there was no significant difference in corneal thickness compared with WT rabbits. Anterior segment ocular coherence tomography and gonioscopic observations revealed an open angle in the OH rabbits. Hematoxylin and eosin (HE) staining together with Masson's trichrome staining showed abnormal collagen accumulation in the angle of the OH rabbit's eyes. Furthermore, aqueous humor (AH) outflow imaging following an intravitreal injection of a fluorescent probe into the anterior chamber for tissue-section analysis revealed retention of the probe in the area of collagen deposition in the OH eyes. The OH rabbits also had a time-dependent increase in the cup/disc ratio. In conclusion, investigations using our newly developed rabbit model of open-angle ocular hypertension showed that abnormal accumulation of extracellular matrix at the angle increased AH outflow resistance in the conventional outflow pathway, leading to a high IOP. Furthermore, the OH rabbits exhibited glaucomatous optic disc cupping over time. These findings suggest the utility of the OH rabbits as a model for open-angle glaucoma (OAG).

Aqueous and Plasma Levels of Phosphorylated Tau 181 in Individuals with Normal Cognition.

Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer's disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between aqueous concentrations, plasma concentrations, and MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p = 0.005 and p = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights.