Biomedical subjects

Ron Ofri

Publications and source records attributed to Ron Ofri.

13 recordsLinked to original sources

PubMed2006

Canine meibometry: establishing baseline values for meibomian gland secretions in dogs.

Meibomian lipid secretions are essential in preventing tear evaporation. Disorders of the meibomian glands may therefore play an important role in the pathogenesis of some forms of keratoconjunctivitis sicca (KCS). Until now, meibomian lipid secretions have never been quantitatively evaluated in dogs. With the aim of establishing baseline values of canine meibomian lipid secretions, meibometry was conducted in 42 healthy dogs, 16 of which were Miniature Schnauzers. The mean meibomium level in 84 eyes of the 42 dogs was 179+/-60 Meibometer units. Age, gender and side did not affect the results. However, meibomium levels were significantly lower in the Miniature Schnauzers, a breed that is susceptible to KCS, compared to other breeds. This report demonstrates that meibometry is a simple and minimally invasive technique that may be readily used in conscious dogs to quantify meibomian gland secretions and explicate tear film dynamics in normal and dry canine eyes.

Animals↗

PubMed2006

Development of inner retinal function, evidenced by the pattern electroretinogram, in the rat.

Though the rat is increasingly used as an animal model in ophthalmic research, including the study of glaucoma, little is known about age-related changes in its inner retinal function. The aim of this study was to evaluate these changes in the rat during the first 18 weeks of life. The pattern electroretinogram (PERG) was used to monitor inner retinal activity in 16 developing rats. In each animal, recordings were conducted at ages 3, 5, 7, 11, 14 and 18 weeks to assess age-related changes in function. Signals were evoked by five stimuli of progressively increasing check width (subtending 82-1312 arc minutes of visual angle) that were projected directly onto the fundus through a specially modified ophthalmoscope which allowed visual and manual control of stimulus quality. Poor signal:noise ratio prevented signal analysis at age 3 weeks. Subsequently, PERG amplitude increased significantly, up to 242% (depending on stimulus check width), during weeks 5-11. After peaking at 11 weeks, signal amplitude declined moderately. Signal latency mirrored that of amplitude, decreasing during the first 11 weeks, and then increasing steadily. Latency was not affected by stimulus check width. Age was highly correlated with P1 latency (R(2)=0.80) and moderately correlated with N2 latency (R(2)=0.52). Therefore, we propose that studies of inner retinal diseases (such as glaucoma) in the rat model should use age-matched controls, as electrophysiological results may be confounded by age-related changes. The rat PERG undergoes many of the age-related changes that have been reported in humans, and thus may serve as an animal model to study development of inner retinal function.

Aging↗

PubMed2006

Functional deficits resulting from laser-induced damage in the rat retina.

BACKGROUND AND OBJECTIVES: To determine the threshold for electrophysiological detection of functional changes after laser photocoagulation in rats, and to correlate the functional damage with retinal morphology. STUDY DESIGN/MATERIALS AND METHODS: Argon-laser lesions, covering a quarter or half of the retina, were produced in the right eyes of 25 rats. Eyes were evaluated by flash electroretinography (ERG) and histologically at 3, 21, and 60 days after lasering. RESULTS: Lasering of half the retina, but not of a quarter, produced a significant decrease in signals at all time points. Some functional recovery was evident 60 days after injury, and was consistent with concurrent morphological healing. CONCLUSIONS: In rats, lasering of half the retina, but not a quarter, leads to significant deficits in outer retinal functions over a 2-month period. Thereafter some recovery occurs, presumably as a result of migration of photoreceptors from undamaged areas and their retinal remodeling.

Animals↗

PubMed2005

T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure.

Acute or chronic glaucoma is often associated with an increase in intraocular pressure (IOP). In many patients, however, therapeutic pressure reduction does not halt disease progression. Neuroprotection has been proposed as a complementary therapeutic approach. We previously demonstrated effective T-cell-based neuroprotection in experimental animals vaccinated with the synthetic copolymer glatiramer acetate (copolymer-1, Cop-1), a weak agonist of self-antigens. This study was undertaken to test different routes and modes of vaccination with Cop-1 as treatment modalities for protection against retinal ganglion cell (RGC) death caused by chronic elevation of IOP in rats, and to determine whether anatomical neuroprotection is accompanied by functional neuroprotection. In a chronic model of unilaterally high IOP, Cop-1 vaccination, with or without an adjuvant, protected rats against IOP-induced loss of RGCs by eliciting a systemic T-cell-mediated response capable of cross-reacting with self-antigens residing in the eye. In rats deprived of T cells, Cop-1 (unlike treatment with alpha2-adrenoreceptor agonists) was not protective of RGCs, substantiating the contention that its beneficial effect is not conferred directly but is T-cell-mediated. Pattern electroretinography provided evidence of functional protection. Thus, vaccination with adjuvant-free Cop-1 can protect RGCs from the consequences of elevated IOP in rats. This protection is manifested both morphologically and functionally. These findings can be readily implemented for the development of a therapeutic vaccination to arrest the progression of glaucoma.

Adjuvants, Immunologic↗

PubMed2005

Pattern electroretinography in a rat model of ocular hypertension: functional evidence for early detection of inner retinal damage.

With the increasing use of the rat as an animal model for glaucoma and for the evaluation of neuroprotective treatments, there is a need for a sensitive test of retinal ganglion cell (RGC) function in this species. The aims of this study were to detect functional abnormalities of the inner retina in a rat model of high intraocular pressure (IOP) using the pattern electroretinogram (PERG), and to correlate them with morphometric analysis of RGC survival and the functional integrity of the inner retina. Unilateral ocular hypertension was induced in 17 Lewis rats through laser photocoagulation. Pattern ERGs were recorded prior to lasering and 3 weeks later, using a series of shifting patterns of decreasing spatial frequency projected directly onto the animals' fundus. IOP was measured at the same intervals, and the number of surviving RGCs estimated. Low amplitude PERG signals could be recorded in response to a narrow grating of 0.368 cycles per degree (cpd), and increased with stimulus size. Lasering caused mean (+/-s.d.) IOP to increase significantly from 18.3+/-4.5 (baseline) to 29.8+/-8.8 mmHg within 3 weeks (p<0.0001). At this time, PERG amplitudes were significantly reduced (p<0.05), declining an average of 45% compared to the normotensive, control eyes. No outer retinal damage was observed, but the mean number of RGCs decreased significantly (p<0.001), from 2 525.0+/-372.4 to 1 542.8+/-333.8 cells per mm2. This decrease in RGC number was significantly (p=0.03) correlated the decrease in PERG amplitude. The correlation between functional integrity of the inner retina and the rat PERG was further demonstrated by intravitreal tetrodotoxin injections, which temporarily abolished the PERG but did not affect outer retinal activity, reflected in the flash ERG. The evidence for early functional deficits, combined with tonometry and documentation of correlated ganglion cells loss, confirms the sensitivity of this diagnostic tool and the validity and importance of this animal model in glaucoma research.

Animals↗

PubMed2004

High-resolution functional optical imaging: from the neocortex to the eye.

Much work remains to be done to establish the clinical usefulness of the RFI for early diagnosis and treatment guidance. The discoveries obtained by functional optical imaging of the neocortex in the last 15 years and the recent RFI studies of the eyes of normal subjects and patients with diabetic retinopathy, glaucoma, and age-related macular degeneration suggest that functional optical imaging of the retina is likely to become a multi-modality powerful clinical tool.

Animals↗

PubMed2003

Functional damage to inner and outer retinal cells in experimental glaucoma.

PURPOSE: To investigate the cellular sources underlying the functional damage observed by multifocal electroretinography (mfERG) responses of glaucomatous eyes of monkeys. METHODS: First- and second-order (K1 and K2, respectively) mfERG responses of three normal and three experimentally induced glaucomatous eyes of cynomolgus monkeys were measured at two different levels of luminance. Retinal contributors to the responses were isolated by intravitreal injections of pharmacological agents that suppress specific retinal cells. gamma-Aminobutyric acid (GABA) and glycine were administered to block inner retinal function, followed by 2-amino-4-phosphonobutyric acid (APB), to block ON-bipolar cells. RESULTS: An inner retinal component removed by GABA and glycine was found in both the normal and glaucomatous eyes. However, it was attenuated in the latter, correlating with changes observed in the baseline K1 responses. Delays in the latency of outer retinal components were found in the responses of the glaucomatous eyes. K2 responses were dominated by an inner retinal contribution and were diminished in the responses of glaucomatous eyes. The outer retina responded to increased luminance with a shorter implicit time. A distinct wave part of the inner retinal component responded to increased luminance with increased amplitudes. CONCLUSIONS: The integration of the retinal sources forming the mfERG response was compared between normal and glaucomatous monkey eyes. Both inner and outer retinal functions were aberrant in the responses of the glaucomatous eyes, with the attenuation of the inner retinal function more conspicuous. Nevertheless, glaucomatous eyes retained certain inner retinal activity, despite the advanced stage of disease. K2 responses were more sensitive to glaucomatous changes than were K1 responses.

Aminobutyrates↗

PubMed2002

Intraocular pressure and glaucoma.

Aqueous humor is a transparent fluid that fills the anterior and posterior chambers, and the pupil, of the eye. It is produced in the ciliary processes, and exits the eye through two major pathways--the iridocorneal (conventional) outflow, and the uveoscleral (unconventional) outflow. Equilibrium between production and drainage of aqueous humor enables the body to maintain constant intraocular pressure (IOP). Disruption of aqueous outflow, usually through the conventional pathway, results in elevation of IOP. This elevation in IOP is a major risk factor in the pathogenesis of glaucoma, a group of diseases characterized by decreased retinal function and progressive optic nerve damage that may result in blindness. This article reviews the anatomy and physiology of aqueous dynamics in exotic species, the causes, clinical signs and diagnosis of glaucoma, and therapeutic approaches.

Animals↗

PubMed2002

Clinical electrophysiology in veterinary ophthalmology--the past, present and future.

The aim of this review is to introduce the reader to the world of clinical veterinary electroretinography. An important indication for ERG recordings in the dog is the early diagnosis of progressive retinal atrophy, an inherited form of photoreceptor degeneration, analogous to retinitis pigmentosa in humans. In most of the 20 canine breeds in which the disease has been studied electrophysiologically, changes in the ERG appear long before the appearance of clinical signs. This early diagnosis is a vital tool in efforts to eradicate the disease through preventive breeding. Pre-operative screening of canine cataract patients is another common indication for electroretinography in the dog. The ERG is also used to diagnose inherited and nutritional photoreceptor degenerations in the cat, and retinal disorders in a number of other animal species. The abundance of animal species (and breeds) seen by the veterinary ophthalmologist lends additional importance to the problem of a harmonized ERG recording protocol. The European College of Veterinary Ophthalmologists has set up a special committee to formulate guidelines for such a protocol. International meetings and wetlabs are also being organized as part of an effort to improve the quality of electrophysiological diagnosis that veterinary ophthalmologists provide their patients.

Animals↗

PubMed2002

Guidelines for clinical electroretinography in the dog.

These procedures described for the dog ERG were approved at the 1st European Conference on Veterinary Visual Electrophysiology in Vienna, Austria, May 30, 2000. Dr. Narfström was Chair of the Committee for a Harmonized ERG Protocol, appointed by the European College of Veterinary Ophthalmology (ECVO), and Dr. Ofri was secretary. The other coauthors are committee members. Guidelines for ERG procedures in other animal species for clinical and laboratory studies are planned for in the future and the present guidelines are planned to be revised on a biannual basis. A brief report of the recommended procedures is available in the Conference Proceedings book.

Animals↗

PubMed2002

Technical issues in electrodiagnostic recording.

Electroretinogram (ERG) and visual-evoked potentials (VEPs) are used in veterinary ophthalmology to assess the functional integrity of the retina and the central visual pathway. The interpretation of altered electrophysiologic potentials in diseases can be of great diagnostic value, although it is important to be aware of technical factors and the limitations of these techniques which may result in over-interpretation and misinterpretation of the recordings, such that they are similar to those found in disease-related electrophysiologic changes. The recorded potentials represent the differences in voltage between the active and reference electrodes. The ground electrode serves as zero. A differential or instrumentation amplifier selectively amplifies signals of interest while rejecting noise. Differences between inputs are amplified, whereas common signals are rejected in a process called common mode rejection (CMR). In order for CMR to be most effective in reducing noise, the electrode impedances should be balanced. Filters are part of the differential amplifier as they remove unwanted noise of a certain frequency. The frequency bandwidth, or passband, is the range of frequencies between low- and high-frequency filter settings that are not filtered out. Major sources of noise that cause interpretation artifacts are power lines, amplifier noise, physiologic activity, electrochemical electrode noise and circular grounds. Noise reduction is achieved with high amplifier input impedance, balanced electrode impedances, CMR, filters and signal averaging. Maintaining electrodes in good condition, achieving proper contact between electrode and animal, and keeping electrode leads short aid in achieving noise reduction.

Animals↗

PubMed2002

Effect of reproductive status on intraocular pressure in cats.

OBJECTIVE: To measure intraocular pressure (IOP) and progesterone concentrations in cats and to examine their reproductive organs to determine whether reproductive status affects IOP in cats. ANIMALS: 75 sexually intact domestic shorthair cats scheduled to be neutered, including 28 males, 21 females not in estrus, 13 females in estrus, and 13 pregnant females. PROCEDURES: Applanation tonometry was conducted to measure IOP and radioimmunoassay was used to determine progesterone concentrations. Reproductive organs were examined at time of surgery. RESULTS: The IOP in female cats that were in estrus was significantly higher than IOP in female cats that were not in estrus. Progesterone concentrations significantly affected IOP in pregnant cats. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, IOP is affected by changes in reproductive status. Such changes should be considered when interpreting tonometry results in this species.

Animals↗

PubMed2002

The effect of contrast and luminance on mfERG responses in a monkey model of glaucoma.

PURPOSE: To evaluate the effect of contrast and luminance attenuation on the multifocal electroretinogram (mfERG) responses of normal and glaucomatous eyes of cynomolgus monkeys. METHODS: Nine adult male cynomolgus monkeys with unilateral experimentally induced glaucoma were used. Hypertension-induced damage was confirmed by tomography of the optic disc. mfERGs were recorded with five different stimulus contrasts and/or luminance settings. The first-order and the first slice of second-order responses were analyzed. RESULTS: Waveforms of normal and glaucomatous eyes differed in shape and amplitude. Second-order responses contributed to first-order responses of the signals in the normal eyes, but made a negligible contribution to the signals in the glaucomatous eyes. Contrast and luminance attenuation affected both first- and second-order responses. The differences between signals in normal and glaucomatous eyes were sufficiently large for an unsupervised clustering algorithm to achieve accurate segregation. CONCLUSIONS: The observations in this study indicate that outer and inner retinal generators participate in first-order mfERG responses and that both inner and outer retinal contributors respond to contrast and luminance changes in stimulus. The hypertension-induced changes in the mfERG furthermore suggest damage to both inner and outer retina.

Animals↗