Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of either drug would provide and sustain the purported therapeutic plasma concentration of buprenorphine (1 ng/mL) over 72 h in nude mice and to characterize the injection site histopathology.
View Article and Find Full Text PDFPurpose: To test the hypothesis that mild chronic hyperoxia treatment would improve retinal function despite a progressive decline in ocular blood flow in the DBA/2J mouse model of glaucoma.
Materials And Methods: DBA/2J mice were treated with chronic mild hyperoxia (30% O2) beginning at 4.5 months of age or were untreated by giving normal room air.
Episcleral venous pressure (EVP) is important for steady state intraocular pressure (IOP), as it has to be overcome by aqueous humor in order to leave the eye. Recent evidence suggests a neuronal tone being present, as topical anesthesia lowered EVP. The superior salivatory nucleus in the brainstem could be identified to elicit increases in EVP during electrical stimulation.
View Article and Find Full Text PDF: To evaluate whether optical imaging methods and histology can detect comparable vascular and neuronal damage in the retina due to the effects of progressive chronic hypertension on the retinal vasculature and neurons using the spontaneously hypertensive rat (SHR) model at young and old ages. : Male SHR and normotensive Wistar Kyoto (WKY) rats were studied at 10 and 40 weeks of age (n = 6 each group). Arterial blood pressure was measured with a tail-cuff.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
March 2016
Purpose: To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma.
Methods: Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice under isoflurane anesthesia using magnetic resonance imaging. Ocular blood flow was measured at baseline, and 1 and 2 hours after topical dorzolamide.
Purpose: To assess the potency and sterility of ophthalmic antibiotic drops commonly used in the treatment of bacterial keratitis.
Methods: This was a basic investigation. Three drugs were tested: fortified vancomycin 25 mg/mL, fortified tobramycin 14 mg/mL, and moxifloxacin 5 mg/mL.
J Ocul Pharmacol Ther
April 2015
Purpose: AR-13324 is a potential new drug for the treatment of patients with glaucoma that has been shown to lower intraocular pressure (IOP) by increasing trabecular outflow facility and decreasing aqueous production. The present study tested the hypothesis that AR-13324 also lowers IOP by reducing episcleral venous pressure (EVP).
Methods: In Dutch Belted (DB) rabbits (n=11), arterial pressure (AP), IOP, carotid blood flow (BFcar), heart rate (HR), and EVP were measured invasively.
Purpose: To verify that a visual fixation protocol with cued eye blinks achieves sufficient stability for magnetic resonance imaging (MRI) blood-flow measurements and to determine if choroidal blood flow (ChBF) changes with age in humans.
Methods: The visual fixation stability achievable during an MRI scan was measured in five normal subjects using an eye-tracking camera outside the MRI scanner. Subjects were instructed to blink immediately after recorded MRI sound cues but to otherwise maintain stable visual fixation on a small target.
Invest Ophthalmol Vis Sci
January 2014
Purpose: Previous experiments have shown that arginine-vasopressin (AVP) reduces intraocular pressure (IOP) dose-dependently. The present study investigated the relationships between IOP, ciliary blood flow (CilBF), and aqueous flow (AqF) responses to AVP in anesthetized rabbits.
Methods: CilBF was measured by laser Doppler flowmetry and AqF by fluorophotometry.
Invest Ophthalmol Vis Sci
October 2013
Purpose: Histological evidence suggests a role for the central nervous system in controlling episcleral venous pressure (EVP). Based on prior studies that identified candidate regions in the brain stem, the present study assessed the effect of electrical stimulation at the location of the superior salivatory nucleus (SSN) on EVP in rats.
Methods: Male Sprague-Dawley rats (n = 11) were anesthetized using pentobarbital sodium (50 mg/kg intraperitoneally initially, supplemented intravenously [IV] as needed) and paralyzed with gallamine triethiodide (1 mg/kg, IV).
Purpose: We tested the hypothesis that retinal blood flow has a postocclusive reactive hyperemia response modulated by occlusion duration and metabolic activity, and that choroidal blood flow does not.
Methods: Anesthetized and paralyzed rats (n = 34) were studied. Retinal and choroidal blood flow was measured by laser speckle imaging and laser Doppler flowmetry, respectively.
Blood flow (BF) in many tissues is stable during significant fluctuations in systemic arterial blood pressure or perfusion pressure under normal conditions. The regulatory mechanisms responsible for this non-passive BF behavior include both local and neural control mechanisms. This study evaluated cerebral BF (CBF), retinal BF (RBF) and choroidal BF (ChBF) responses to acute blood pressure increases in rats using magnetic resonance imaging (MRI).
View Article and Find Full Text PDFPurpose: This study tests the hypothesis that reduced retinal and choroidal blood flow (BF) occur in the DBA/2J mouse model of glaucoma.
Methods: Quantitative BF magnetic resonance imaging (MRI) with a resolution of 42 × 42 × 400 μm was performed on DBA/2J mice at 4, 6, and 9 months of age and C57BL/6 age-matched controls under isoflurane anesthesia. BF MRI images were acquired with echo-planar imaging using an arterial spin labeling technique and a custom-made eye coil at 7 Tesla.
Nitroprusside, a vasodilatory nitric oxide donor, is clinically used during vascular surgery and to lower blood pressure in acute hypertension. This article reports a novel application of blood flow (BF) and blood oxygenation level dependent (BOLD) MRI on an 11.7T scanner to image the rat chorioretinal BF and BOLD changes associated with graded nitroprusside infusion.
View Article and Find Full Text PDFMicrovasculature hemoglobin oxygen saturation (SaO2) is important in the progression of various pathologies. Non-invasive depth-resolved measurement of SaO2 levels in tissue microvasculature has the potential to provide early biomarkers and a better understanding of the pathophysiological processes allowing improved diagnostics and prediction of disease progression. We report proof-of-concept in vivo depth-resolved measurement of SaO(2) levels in selected 30 µm diameter arterioles in the murine brain using Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) with 800 nm and 770 nm photothermal excitation wavelengths.
View Article and Find Full Text PDFPurpose: To investigate the effects of arginine-vasopressin (AVP) on intraocular pressure (IOP), orbital venous pressure (OVP), and choroidal blood flow (ChorBF) regulation in anesthetized rabbits.
Methods: Mean arterial pressure (MAP), IOP, and OVP were measured by direct cannulation of the central ear artery, the vitreous, and the orbital venous sinus, respectively. Laser Doppler flowmetry was used to record ChorBF.
Purpose: To demonstrate lamina-specific functional magnetic resonance imaging (MRI) of retinal and choroidal responses to visual stimulation of graded luminance, wavelength, and frequency.
Materials And Methods: High-resolution (60 × 60 μm) MRI was achieved using the blood-pool contrast agent, monocrystalline iron oxide nanoparticles (MION) and a high-magnetic-field (11.7 T) scanner to image functional changes in the normal rat retina associated with various visual stimulations.
Purpose: To demonstrate blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) of vascular oxygenation changes in normal, unanesthetized human retinas associated with oxygen and carbogen challenge.
Methods: MRI was performed with a 3-T human scanner and a custom-made surface-coil detector on normal volunteers. BOLD MRI with inversion recovery was used to suppress the vitreous signal.
Invest Ophthalmol Vis Sci
March 2010
Purpose: To determine the episcleral venous pressure (EVP) responses to nitroprusside (NP) and L-NAME.
Methods: In anesthetized rabbits (n = 36), arterial pressure and IOP were measured by direct cannulation, and carotid blood flow and heart rate were measured with an ultrasound flowmeter and cardiotachometer. EVP was measured in two groups with a servonull system.
Purpose: To determine the effects of topical dorzolamide (a carbonic anhydrase inhibitor) on choroidal and ciliary blood flow and the relationship between ciliary blood flow and aqueous flow.
Methods: The experiments were performed in four groups of pentobarbital-anesthetized rabbits treated with topical dorzolamide (2%, 50 microL). In all groups, intraocular pressure (IOP) and mean arterial pressure (MAP) at the eye level were measured continuously by direct cannulation.
Invest Ophthalmol Vis Sci
June 2009
Purpose: To determine the effect of proparacaine-induced topical anesthesia on episcleral venous pressure (EVP).
Methods: In anesthetized rabbits (n = 11), EVP was measured with a servonull micropressure system, with glass pipettes with 2- to 3-microm tips used to cannulate episcleral veins. Additional measurements included arterial, intraocular, and orbital venous pressures obtained by direct cannulation, to assess the ocular pressure gradients, and carotid blood flow and heart rate, to verify preparation stability.
J Ocul Pharmacol Ther
February 2007
Purpose: The aim of this study was to assess the effects of acute systemic, nonselective alpha-adrenergic blockade on aqueous flow.
Methods: This study used pentobarbital-anesthetized rabbits (n=7), in which the following parameters were measured: mean arterial pressure, carotid blood flow, heart rate, intraocular pressure (IOP), orbital venous pressure (OVP), ciliary blood flow, and aqueous flow (AqFlow). Measurements were made before and after an intravenous administration of phentolamine (0.
This review will summarize the authors' recent studies of the relationship between ciliary blood flow and aqueous production, and discuss the relevance of that relationship to the mechanisms of action of glaucoma drugs that lower intraocular pressure by inhibiting aqueous production. The ciliary processes are not easily accessible, and so the data presented necessarily come from animals and from instrumentation operated at its engineering limits. Verification of the findings in humans, and perhaps refinement of the interpretations, must await future advances in technology.
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