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Biomedical subjects

Eyal Banin

Publications and source records attributed to Eyal Banin.

23 records · Page 2Linked to original sources

Gene delivery by viral vectors in primary cultures of lacrimal gland tissue.

PURPOSE: To test the feasibility of gene transfer into lacrimal gland tissue in primary culture, using different viral vectors. METHODS: Lacrimal glands were dissected from adult Sabra rats and divided by pincers to 0.3-0.4 mm fragments. Tissue was maintained under primary organ culture conditions using the "raft" technique. The ability of three different viral vectors to conduct beta-galactosidase (beta-gal) gene delivery was examined: adenovirus (Ad5CMVLacZ), vaccinia (VSC9), and herpesvirus (tkLTRZ(1)). Tissue fragments were incubated for 60 minutes with one of the viral vectors and transferred to fresh medium. After 3 and 7 days, beta-gal expression was examined by X-gal staining in gross preparations and in histologic sections. RESULTS: At 3 days, beta-gal expression was observed in 33% of tissue fragments exposed to the vaccinia vector and in 18% and 14% of fragments exposed to the adenoviral and herpes vectors, respectively. After 7 days in culture, successful gene delivery occurred in 77% of vaccinia, 41% of adenovirus, and only 13% of herpesvirus applications. Vector-specific reporter gene expression patterns were observed: With the vaccinia vector, lacrimal duct cells were predominantly stained; in contrast, the adenoviral vector tended to transduce the interacinar areas, with beta-gal expression mainly occurring within the myoepithelial cells. CONCLUSIONS: Vaccinia and adenovirus are efficient vectors for gene transfer into lacrimal gland tissue in primary culture. The specific expression pattern obtained by the vaccinia vector probably reflects its characteristic tissue tropism to lacrimal duct cells. The results presented in this ex vivo system may be a first step toward expressing genes with products that could be continuously delivered to the eye through the tears. Such proteins could include anti-inflammatory, anti-angiogenic, anti-herpetic, anti-bacterial, or anti-glaucomatous agents, among others.

Adenoviridae↗

Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard.

PURPOSE: Mustard agents are highly toxic and abundant warfare chemicals, primarily affecting ocular tissues, with no specific treatment antidote. The purpose of the present study was to examine the efficacy of novel metallocomplexes, known to inhibit the formation of highly reactive free radicals, to reduce ocular injury induced by nitrogen mustard (NM). METHODS: One eye in each of 72 rabbits was exposed to 1% to 2% NM. Topical treatment with eye drops of a metallocomplex--either zinc- or gallium-desferrioxamine (Zn/DFO and Ga/DFO)--was compared with treatment with saline, zinc (chloride), or DFO alone. Examiners masked to the treatment groups assessed the extent of ocular injury and the response to treatment using clinical, histologic, and biochemical criteria. RESULTS: Exposure to NM followed by administration of carrier alone (saline) caused severe and long-lasting injury to ocular anterior segment structures. Treatment with either Zn/DFO or Ga/DFO yielded marked protection (52%-64%), including faster healing of corneal epithelial erosions, less scarring and neovascularization, decreased inflammation in the anterior chamber, better maintenance of intraocular pressure, and less severe changes in the iris and lens. These were also associated with better preservation of systemic antioxidant status. Zinc or DFO alone afforded lower levels of protection. No toxic effects of these complexes were observed. CONCLUSIONS: It is suggested that Zn/DFO or Ga/DFO, by virtue of their enhanced ability to infiltrate cells and inhibit transition metal-dependent formation of free radicals through the combined push-pull mechanism, be considered as a basis for treatment of mustard injuries.

Administration, Topical↗

[Experimental therapeutic modalities for retinitis pigmentosa].

Retinitis Pigmentosa (RP) is a heterogeneous group of inherited diseases that cause retinal degeneration, often leading to blindness. Over the last decade, the advent of molecular biological techniques has greatly improved our understanding of the genetic and molecular processes underlying these diseases. This has prompted research efforts aimed at the development of novel therapeutic modalities for RP, and the purpose of this review is to present current trends in this field. In this first of two parts, advances in gene therapy, the use of neurotrophic growth factors, and attempts to alter disease progression by vitamins and nutritional modification are discussed. Experimental treatments involving surgical intervention will be addressed in a future, second part of this review that will include the topics of retinal and retinal pigment epithelium transplantation, the potential use of stem cells to replace degenerating retinal cells, and the development of "artificial vision" using electro-optical devices. The encouraging progress made in these various experimental directions lends hope that efficient treatment for at least some of the patients suffering from these blinding diseases is within sight.

Disease Progression↗

[Visual field disturbances in epileptic patients treated with vigabatrin (sevril)].

Vigabatrin, one of the newer anti-epileptic drugs (AED), whose effect is mediated via elevated levels of brain GABA, has proved to be effective in drug resistant partial seizures and infantile spasms. Recently, visual field constriction was found in up to 30% of adults, whereas information for the pediatric age group is sparse. We examined 24 visually-asymptomatic children, ages 3.5-18 years, treated for 3.01.6 years at doses of 25-90 mg/kg. These children underwent an ophthalmologic examination, visual evoked potentials, electroretinogram and when possible, perimetry. Over half of the children had at least one abnormal test and 11/17, who were able to undergo perimetric studies, had symmetrical, nasal visual field constriction. In view of the gravity and prevalence of visual field constriction, use of the AED vigabatrin should be weighed against its clinical benefits.

Anticonvulsants↗

The effect of hormone therapy on the risk for age-related maculopathy in postmenopausal women.

OBJECTIVE: To evaluate the effect of postmenopausal hormone therapy (HT) as well as the use of oral contraceptives and lifetime endogenous hormone exposure on the risk for age-related maculopathy (ARM) in postmenopausal women. DESIGN: This was a cross-sectional, controlled study. A total of 102 women from 60 to 80 years of age who were receiving HT and 100 controls underwent a detailed clinical funduscopic evaluation and stereoscopic fundus photography for the presence and grading of ARM. All participants completed a standardized questionnaire regarding vascular risk factors, HT, and lifetime exogenous and endogenous estrogen and progesterone exposure. Statistical analysis was performed using Student's t test, chi2 test, and a multivariate logistic regression model. RESULTS: The HT and the non-HT groups did not differ in terms of early (11% v 15%), late (6% v 6%), or wet (2% v 2%) ARM prevalence rates. Women with ARM were significantly older than controls (69 v 66 years; P = 0.001, 95% CI = 0.008 - 0.027) and were more likely to have ischemic heart disease (21% v 9%; OR = 2.86, P = 0.03, 95% CI = 0.020 - 0.360). Lifetime exogenous and endogenous hormone exposures and other cardiovascular risk factors were not significantly different among women with ARM as compared with controls. CONCLUSION: Postmenopausal HT may not affect the risk for either early or late ARM in women aged 60 to 80 years. The risk for both entities is not necessarily affected by either exogenous or endogenous lifetime hormone exposure. A history of ischemic heart disease may be associated with an increased risk for ARM.

Age Factors↗