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Biomedical subjects

Gil Ben-Shlomo

Publications and source records attributed to Gil Ben-Shlomo.

4 recordsLinked to original sources

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↗

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↗

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↗

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↗