Dataset Information

Role of Histamine H? Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma.

ABSTRACT: Intraocular pressure (IOP) has a tendency to fluctuate throughout the day, reaching its peak in the early morning in healthy subjects or glaucoma patients. Likewise, histamine tone also fluctuates over time, being lower at nighttime. Numerous studies have demonstrated a correlation between short-term IOP fluctuation and glaucoma progression; however, it has not yet been determined whether histamine plays a role in IOP fluctuations. The aim of this research was to establish the distribution of the histamine receptor proteins and respective mRNAs in the eye by western blot, immunohistochemistry and RT-PCR in New Zealand rabbits. Furthermore, we used a transient ocular hypertension (OHT) model induced by injection of 50 µL of 5% hypertonic saline into the vitreous and a stable OHT model (100 µL 0.1% carbomer in the anterior chamber) to address the potential IOP-lowering ability of H? receptor (H?R) antagonists (ciproxifan, DL76 and GSK189254). IOPs were performed with a Tono-Pen at baseline and 60, 120 and 240 min post treatment after transient OHT induction and, every day for 12 days in the stable OHT model. All histamine receptor subtypes were localized in the rabbit retina and ciliary body/trabecular meshwork. All the treatments lowered IOP in a dose-dependent fashion between 0.3% and 1%. More specifically, the effects were maximal with ciproxifan at 60 min post-dose (IOP60 change = -18.84 ± 4.85 mmHg, at 1%), remained stable until 120 min (IOP120 change = -16.38 ± 3.8 mmHg, at 1%) and decayed thereafter to reach baseline values at 240 min. These effects were highly specific and dependent on histamine release as pre-treatment with imetit (H?R agonist, 1%) or pyrilamine (H?R antagonist, 1%) largely blocked ciproxifan-mediated effects. Color Doppler ultrasound examination was performed to evaluate changes in ophtalmic artery resistivity index (RI) before and after repeated dosing with DL 76, GSK189254, ciproxifan and timolol. Chronic treatments with H?R antagonists and timolol improved the vascular performance of ophthalmic arteries and reduced retinal ganglion cell death. Oxidative stress was also reduced and measured 8-Hydroxy-2'-deoxyguanosine (8OHdG) expression, and by dihidroethydium (DHE) staining. These results demonstrated that the histamine system participates in IOP regulation and that H?R antagonists could represent a future promising therapy for glaucoma. Further studies should be focused on the long-term IOP circadian fluctuations.

SUBMITTER: Lanzi C

PROVIDER: S-EPMC6412827 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Role of Histamine H₃ Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma.

Lanzi Cecilia C Lucarini Laura L Durante Mariaconcetta M Sgambellone Silvia S Pini Alessandro A Catarinicchia Stefano S Łażewska Dorota D Kieć-Kononowicz Katarzyna K Stark Holger H Masini Emanuela E

International journal of molecular sciences 20190224 4

Intraocular pressure (IOP) has a tendency to fluctuate throughout the day, reaching its peak in the early morning in healthy subjects or glaucoma patients. Likewise, histamine tone also fluctuates over time, being lower at nighttime. Numerous studies have demonstrated a correlation between short-term IOP fluctuation and glaucoma progression; however, it has not yet been determined whether histamine plays a role in IOP fluctuations. The aim of this research was to establish the distribution of th ...[more]

PMID: 30813468

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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:BackgroundProspective, multicenter, randomized, double-masked trials have shown latanoprost instilled once daily to be at least as effective as and generally superior to timolol administered twice daily and to be as effective as other frequently prescribed prostaglandin analogues. This study prospectively assessed the efficacy of latanoprost monotherapy in a large cohort of treatment-naive patients with a broad range of baseline intraocular pressure (IOP) levels treated in actual clinical practice settings.MethodsThis prospective, open-label, multicenter, uncontrolled, phase IV study included treatment-naive ocular hypertension or open-angle glaucoma subjects initiating latanoprost once daily (evening). IOP levels were measured at baseline and after 1 and 3 months. The primary efficacy outcome was mean change in IOP from baseline to month 3. Analyses were stratified by baseline IOP: > or = 20 and <24 mmHg vs > or = 24 mmHg.ResultsEfficacy analyses (intent to treat) included 572 subjects: 20 to <24 mmHg group, N = 252; > or = 24 mmHg group, N = 320. Mean baseline IOP levels were 22.2 +/- 0.9 mmHg and 26.7 +/- 2.8 mmHg, respectively. At month 3, significant IOP reductions were seen in both groups (p < 0.0001, within-group differences); reductions were smaller in the 20 to <24 mmHg group (-6.3 +/- 2.4 vs -9.2 +/- 3.7 mmHg, respectively; -28.0 +/- 10.6% vs -34.1 +/- 11.9%, respectively). An IOP reduction of > or = 30% from baseline to month 3 was noted in 48.4% and 65.6% of subjects, respectively (p < 0.0001). At month 3, targets IOPs of < or = 18 mmHg were achieved by > or = 70% of subjects in both groups. Latanoprost was well tolerated with an adverse event profile similar to that reported in the literature.ConclusionsThis "real world" study found once-daily latanoprost to be effective and safe in treatment-naive ocular hypertension or open-angle glaucoma patients. Patients with baseline IOP levels of 20 to <24 mmHg as well as > or = 24 mmHg benefitted from initial latanoprost therapy.Trial registrationTrial registration numberNCT00647101.

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.

Project description:PurposeLongitudinal testing plays a key role in glaucoma management. Variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This study examines whether visual field sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects.DesignComparative case series.ParticipantsA total of 33 873 visits by 1636 participants enrolled in the Ocular Hypertension Treatment Study. Participants were split into 6 geographic zones according to the prevailing climate in their location.TestingAt each visit, standard automated perimetry was conducted on each eye, and IOP was measured.Main outcome measuresMixed effects regression models were formed to look for sinusoidal periodic effects on the change in perimetric mean deviation since the last visit (?MD) and on IOP, both overall and within each zone.ResultsWhen all the data were included, a significant seasonal effect on ?MD was found with magnitude 0.06 dB, peaking in February (P < 0.001). Five of the 6 geographic zones exhibited significant seasonal effects on ?MD, peaking between January and April, with magnitudes ranging from 0.04 dB (P = 0.049) to 0.21 dB (P < 0.001). Zones with greater climactic variation showed larger seasonal effects on ?MD. All 6 zones exhibited a seasonal effect on IOP, peaking in January or February, with magnitudes ranging from 0.14 to 0.39 mmHg (P ? 0.02 in all cases). However, there was no evidence of a significant association between the magnitudes or dates of peaks of the 2 seasonal effects.ConclusionsThe mean deviation was significantly higher in winter than in summer. There is no evidence of an association with seasonal IOP fluctuations. The cause of the seasonal effect on visual field sensitivity is unknown. These findings may help shed light on the glaucomatous disease process and aid efforts to reduce test-retest variability.

Dataset Information

Role of Histamine H? Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma.

Publications

Role of Histamine H₃ Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma.

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