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Endogenous ocular lipids as potential modulators of intraocular pressure.

ABSTRACT: Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary open-angle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data for above classes of lipids. We standardized in vitro assays for rapid characterization of lipids undergoing significant diminishment in disease state. Evaluation of lipids using in vitro assays helped select a finite number of lipids that may potentially expand cellular interstitial space embedded in an artificial matrix or increase fluid flow across a layer of cells. These assays reduced a number of lipids for initial evaluation using a mouse model, DBA/2J with spontaneous IOP elevation. These lipids were then used in other mouse models for confirmation of IOP lowering potential of a few lipids that were found promising in previous assessments. Our results provide selected lipid molecules that can be pursued for further evaluation and studies that may provide insight into their function.

SUBMITTER: Edwards G

PROVIDER: S-EPMC7171415 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Endogenous ocular lipids as potential modulators of intraocular pressure.

Edwards Genea G Arcuri Jennifer J Wang Haiyan H Ziebarth Noel N Zode Gulab G Lee Richard K RK Bhattacharya Sanjoy K SK

Journal of cellular and molecular medicine 20200223 7

Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary open-angle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data f ...[more]

PMID: 32090468

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Project description:The purpose of this study was to develop a method of estimating pulsatile ocular blood volume (POBV) from measurements taken during an ophthalmic exam, including axial length and using a tonometer capable of measuring intraocular pressure (IOP) and ocular pulse amplitude (OPA). Unpublished OPA data from a previous invasive study was used in the derivation, along with central corneal thickness (CCT) and axial length (AL), as well as IOP from the PASCAL dynamic contour tonometer (DCT) and intracameral (ICM) measurements of IOP for 60 cataract patients. Intracameral mean pressure was set to 15, 20, and 35 mmHg (randomized sequence) in the supine position, using a fluid-filled manometer. IOP and OPA measurements were acquired at each manometric setpoint (DCT and ICM simultaneously). In the current study, ocular rigidity (OR) was estimated using a published significant relationship of OR to the natural log of AL in which OR was invasively measured through fluid injection. Friedenwald's original pressure volume relationship was then used to derive the estimated POBV, delivered to the choroid with each heartbeat as a function of OR, systolic IOP (IOPsys), diastolic IOP (IOPdia), and OPA, according to the derived equation POBV = log (IOPsys/IOPdia) / OR. Linear regression analyses were performed comparing OPA to OR and calculated POBV at each of the three manometric setpoints. POBV was also compared to OPA/IOPdia with all data points combined. Significance threshold was p < 0.05. OR estimated from AL showed a significant positive relationship to OPA for both DCT (p < 0.011) and ICM (p < 0.006) at all three manometric pressure setpoints, with a greater slope for lower IOP. Calculated POBV also showed a significant positive relationship to OPA (p < 0.001) at all three setpoints with greater slope at lower IOP, and a significant negative relationship with IOPdia. In the combined analysis, POBV showed a significant positive relationship to OPA/ IOPdia (p < 0.001) in both ICM and DCT measurements with R2 = 0.9685, and R2 = 0.9589, respectively. POBV provides a straight-forward, clinically applicable method to estimate ocular blood supply noninvasively. Higher IOP in combination with lower OPA results in the lowest values of POBV. The simplified ratio, OPA/ IOPdia, may also provide a useful clinical tool for evaluating changes in ocular blood supply in diseases with a vascular component, such as diabetic retinopathy and normal tension glaucoma. Future studies are warranted.

Project description:Purpose: To investigate the relationship between retinal microvasculature changes and intraocular pressure (IOP) for ocular hypertension (OHT) patients and further assess the factors associated with retinal microcirculation changes. Methods: This was a single-center prospective study designed for OHT patients, which consisted of two visits. After collecting baseline data of those who met the eligibility criteria, these patients were treated with latanoprost 0.005% ophthalmic solution for 4 weeks. Peripapillary vessel density (VD) of radial peripapillary capillaries (RPC) layer, macular VD in both superficial and deep layers, and foveal avascular zone (FAZ) area were measured by optical coherence tomography angiography (OCTA) before and after the treatment. We compared the changes in IOP and VD among the two visits by paired-sample t-test. Bonferroni correction was applied. Factors associated with VD changes were analyzed by linear regression analysis. Results: Thirty-four eyes of thirty-four patients were included. The mean IOP decreased by 6.5 ± 2.2 mmHg (p < 0.001). The peripapillary RPC VD increased significantly from 51.8 ± 2.5 to 53.0 ± 3.1% (Adjusted-p = 0.012). We found no significant difference in detailed sectors of the peripapillary region after correction. In the macular area, both the superficial and deep layers in foveal (superficial: 0.2 ± 1.9%, p = 0.523; deep: 0.0 ± 2.3%, p = 0.969) and parafoveal (superficial: 0.3 ± 3.0%, p = 0.565; deep: 0.5 ± 3.1%, p = 0.423) VD remained unchanged. The decrease of the mean FAZ area was insignificant (p = 0.295). The percentage of IOP reduction (β = 0.330, p = 0.031) and the baseline RNFL thickness (β = 0.450, p = 0.004) significantly correlated with the percentage of peripapillary RPC VD improvement in the multivariate linear regression analysis. Conclusion: The peripapillary VD in OHT patients increased after the reduction of IOP. The mild change of IOP did not alter the microcirculation in the macula. In addition, the percentage of IOP change and the baseline RNFL thickness were independent factors for the peripapillary RPC VD improvement.

Project description:PurposeTo determine the 24-hour effects of travoprost with sofZia on intraocular pressure (IOP) and ocular perfusion pressure as well as the endurance of IOP lowering after last dosing.DesignProspective, open-label study.MethodsForty subjects with open-angle glaucoma or ocular hypertension were admitted to our sleep laboratory for three 24-hour sessions monitoring IOP, blood pressure (BP), and heart rate. The first baseline session occurred after medication washout or immediately after enrollment for treatment-naïve patients. A second 24-hour monitoring session was performed after 4 weeks of once-nightly treatment of travoprost with sofZia. The medication was then discontinued and a third 24-hour session was completed 60-84 hours after the last dose taken. IOP measurements were taken using a pneumotonometer every 2 hours in the sitting position during the 16-hour diurnal period and in the supine position during the 8-hour nocturnal period. Ocular perfusion pressure was defined as 2/3[diastolic BP + 1/3(systolic BP - diastolic BP)] - IOP.ResultsTreatment with travoprost with sofZia significantly lowered mean diurnal and nocturnal IOP levels from baseline (diurnal 18.1 ± 3.9 to 15.3 ± 3.3 mm Hg; nocturnal 20.6 ± 3.6 to 19.4 ± 3.4 mm Hg, P < .01 for both). Once treatment was discontinued, mean IOP remained at levels significantly less than baseline during both the diurnal (16.6 ± 3.8 mm Hg) and nocturnal periods (19.4 ± 3.5 mm Hg). Mean baseline ocular perfusion pressure was significantly increased during the diurnal but not the nocturnal period (diurnal 73.7 ± 11.4 to 76.5 ± 10.3 mm Hg, P = .01; nocturnal 64.4 ± 12.6 to 64.2 ± 11.1 mm Hg, P = .67).ConclusionTravoprost with sofZia significantly lowers IOP throughout the diurnal and nocturnal periods, and increases ocular perfusion pressure in the diurnal, but not the nocturnal, period in open-angle glaucoma and ocular hypertension. The treatment effect on IOP endures for at least 84 hours after the last dose.

Project description:PurposeSerum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP).DesignCross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts.ParticipantsWe included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009.MethodsMultivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc).Main outcome measuresCorneal-compensated IOP.ResultsHigher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06-0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08-0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05-0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07-0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03-0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06-0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (-0.05 mmHg; 95% CI, -0.08 to -0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30).ConclusionsOur findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

Project description:PurposeTo describe variability of intraocular pressure (IOP) measurements within the same eye and between right and left eyes over a 60-month period in participants in the Ocular Hypertension Treatment Study.DesignAnalysis of data from a prospective, randomized clinical trial.ParticipantsEight hundred ten participants randomized to the observation group.MethodsIntraocular pressure measurements were obtained at the baseline visit and every 6 months thereafter. Pearson correlation coefficients were calculated for IOP measurements in the same eye between visits and for IOP measurements between right and left eyes of participants at each visit. Differences in IOP measurements between visits are reported in percent change (>15%, >20%, and >30%) and in millimeters of mercury (<3 mmHg, 3-5 mmHg, and >5 mmHg). The effects of regression to the mean, consistency in time of day, and sequence of IOP measurement of right and left eyes were examined.Main outcome measuresCorrelation of IOP measurements between consecutive 6-month visits.ResultsThe correlation of IOP measurements within the same eye between consecutive visits was r = 0.62, whereas the correlation of IOP measurements between right and left eyes at the same visit was r = 0.72. Thirteen percent of eyes had >20% change in IOP between consecutive visits. Sixty-six percent of eyes had a change in IOP within 3 mmHg, and 10% of eyes had a change in IOP >5 mmHg between visits. Eyes with a higher baseline IOP had a lower IOP at 6 months. There was a stronger correlation of IOP measured within 2 hours of the time of day between visits (r = 0.56) than >2 hours apart (r = 0.39). IOP of the right eye, which was measured first, was 0.3+/-2.8 mmHg higher than the left eye.ConclusionsThe variability of IOP measurements in the same eye between consecutive visits is moderate and is greater than the variability of IOP measurements between right and left eyes at the same visit. Factors affecting the variability of IOP measurement include regression to the mean, time of day, and measurement order. Knowledge of variability in IOP and its measurements may help clinicians establish a more accurate baseline IOP, target IOP, and assessment of medication effect.

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Endogenous ocular lipids as potential modulators of intraocular pressure.

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Endogenous ocular lipids as potential modulators of intraocular pressure.

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