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Biomedical subjects

Eyal Aloni

Publications and source records attributed to Eyal Aloni.

6 recordsLinked to original sources

A rat model for acute rise in intraocular pressure: immune modulation as a therapeutic strategy.

PURPOSE: To establish a rat model of acute increase in intraocular pressure (IOP) and to investigate the therapeutic window for protection against death of retinal ganglion cells (RGCs) by vaccination with glatiramer acetate (Cop-1) or by treatment with brimonidine or MK-801. DESIGN: Animal study, laboratory investigation. METHODS: IOP was transiently increased in anesthetized Lewis rats by infusing normal saline (0.9%) into the anterior chamber of the eye for one hour. RGC survival was assessed one week and two weeks later by counting the RGCs retrogradely labeled with rhodamine dextran. MAIN OUTCOME MEASURES: RGC survival. RESULTS: IOP rose to 100 cm H(2)O (76 mm Hg) and returned to baseline after 24 hours. The RGC count decreased by 23% a week after the insult and by a further 7% after the second week. Vaccination with Cop-1 on the day of the insult prevented 50% of the IOP-induced RGC loss. Similar neuroprotection was achieved by daily intraperitoneal injections of brimonidine, but not with MK-801. CONCLUSIONS: A transient increase in IOP to 100 cm H(2)O causes death of RGCs in rats. A single immunization with Cop-1 or daily injections of brimonidine protected up to 50% of potentially doomed RGCs from IOP-induced death, suggesting that not all of the cell death in the untreated model results from the IOP insult directly, but that some of it is caused by insult-induced environmental cytotoxicity, which is unrelated to glutamate toxicity or at least to NMDA receptors. These findings can be applied immediately as a basis for acute glaucoma therapy.

Acute Disease↗

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↗

[Intravitreal triamcinolone acetonide for diffuse diabetic macular edema--one year follow-up].

BACKGROUND: Macular edema is the main cause of visual impairment in diabetic patients. Its treatment is mainly based on laser photocoagulation. Intravitreal triamcinolone acetonide (TA) has recently been proposed as a new treatment for eyes with diabetic macular edema resistant to conventional laser photocoagulation. AIM: To evaluate the one year efficacy and safety of a single TA injection administered for diffuse diabetic macular edema unresponsive to prior laser treatment. DESIGN: Interventional case series. METHODS: Setup: University medical center out-patient clinic. PARTICIPANTS: Twenty-one patients with bilateral diffuse diabetic macular edema. INTERVENTION: A single intravitreal injection of triamcinolone acetonide. MAIN OUTCOME MEASURES: Visual acuity measured by ETDRS score, retinal area evaluation clinically and retinal thickness evaluation by Retinal Thickness Analysis (RTA) at 3 and 12 months following injection. Secondary outcomes were intraocular pressure control and cataract progression. RESULTS: Three months following injection, the mean improvement in visual acuity was 4.7 +/- 11.7 letters in the study group as compared to 0.2 +/- 11.4 in the control group (p = 0.18). No difference was noticed one year following injection. Clinical assessment of the retinal area of edema revealed a substantial difference between patients and controls at 3 months (p = 0.0006) and at one year (p = 0.05). RTA evaluation revealed improvement in retinal thickness solely at the 3 months exam. Four eyes developed high intraocular pressure and required treatment (p = 0.054). No difference in cataract progression was noted between the two groups (p = 0.69). CONCLUSIONS: Injection of TA may improve visual acuity for a limited time. Increased intraocular pressure is a frequent side effect. During a one year follow-up, no evidence of ocular toxicity was noted in eyes with diffuse diabetic macular edema.

Anti-Inflammatory Agents↗

Eyelid bleeding and atypical amyloidosis.

PURPOSE: To describe a case of atypical systemic amyloidosis in a patient who presented with recurrent subcutaneous bleeding of the eyelids and auricles. DESIGN: Observational case report. METHODS: A 52-year-old man with chronic cardiac failure, hypertension, weight loss, and impotence presented with recurrent bleeding of the eyelids and auricles, and was investigated for suspected amyloidosis. RESULTS: Biopsy specimens taken from the bone marrow, salivary gland, abdominal subcutaneous fat, and gastric mucosa, and eyelids were all negative for Congo red. Results of a conjunctival biopsy, which were returned after the patient's death, and cardiac muscle autopsy were positive for Congo red staining, indicating amyloidosis. CONCLUSION: The findings in this case show that the presentation of amyloidosis may be atypical. Ophthalmologists should consider a diagnosis of amyloidosis in patients with periorbital bleeding, even if biopsies are negative for Congo red. A conjunctival biopsy may be useful in establishing a diagnosis of primary systemic amyloidosis.

Amyloidosis↗

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↗

Special report: Noninvasive multi-parameter functional optical imaging of the eye.

Advancement in the treatment of blindness depends on the development of new technologies that enable early detection, follow-up, and treatment of disease. The authors describe direct, noninvasive imaging of four parameters: blood flow, blood oximetry, metabolic state, and hidden vasculature, particularly capillaries. These are functional parameters of the retina known to be degraded by retinal disease. The new Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel) can image all four parameters as intrinsic reflectance intensity differences over the retina's surface. During the past 2 decades, imaging of small optical signals has been a powerful tool for high-resolution functional mapping in the neocortex. In this article, this technology is applied to the retina and demonstrates a general tool for noninvasively probing retinal function in many modalities. Imaging functional changes before anatomic consequences arise holds promise as a powerful tool for early diagnosis and treatment of retinal disease.

Adult↗