Original article
Effect of Triamcinolone Acetonide on Vascular Endothelial Growth Factor and Occludin Levels in Branch Retinal Vein Occlusion

https://doi.org/10.1016/j.ajo.2008.12.006Get rights and content

Purpose

To investigate the molecular mechanism by which triamcinolone acetonide (TA) may reduce edema in a porcine model of branch retinal vein occlusion (BRVO).

Design

Animal study.

Method

After baseline ophthalmoscopic examination and fundus photography, a BRVO was created photothrombotically in each eye of 6 pigs, using argon green photocoagulation and intravenous Rose Bengal. Following this, the left eye was injected intravitreally with 4 mg/0.1 ml TA. After 11 weeks, the eyes were re-examined. Fluorescein angiography, in addition to ophthalmoscopy and fundus photography, was performed. Following sacrifice of the animals, the eyes were enucleated and processed. The distribution of vascular endothelial growth factor (VEGF), occludin, and glial fibrillary acidic protein (GFAP) were localized by immunofluorescence cytochemistry on 10 μm frozen retinal sections of TA-treated and untreated eyes.

Results

Retinal VEGF levels were significantly lower in the TA-treated eyes as compared with the untreated eye (P = .002). Conversely occludin levels were significantly higher in the treated eye (P = .026). There was also a significant reduction in GFAP immunoreactivity in the Muller cells of the treated eyes (P = .015) with no statistical significance in the astrocytes (P = .065).

Conclusion

Intravitreal TA down regulates VEGF, which may prevent a decrease in occludin and also inhibits an increase in GFAP expression in Muller cells. These events may contribute to a reduction in the blood retinal barrier breakdown that occurs in BRVO and promote resolution of the associated retinal edema.

Section snippets

Methods

Six live pigs (age, 4 weeks; body weight, ∼10 kg) were used in this study.

Clinical

Ophthalmoscopy demonstrated no ocular abnormality in any eye at baseline. Following laser photothrombosis, all of the treated and all of the untreated eyes showed immediate signs of a BRVO with venous stagnation, retinal hemorrhages, and swelling. At the 11-week examination, all the eyes showed evidence of a previous BRVO. Vein to vein single or multiple shunts were seen respectively in 5 (83.3%) treated and 4 (66.6%) untreated eyes of 6 eyes, respectively (Figure 1). All the remaining eyes

Discussion

We have established a technique that successfully creates BRVOs with subsequent hemorrhages and edema using argon green laser photocoagulation in animal models including dog,12 rat,13 and pig (unpublished data). Danis and associates14 also successfully created laser-induced BRVOs that showed severe tortuosities, venous congestion, intraretinal hemorrhages, and retinal edema that resolved itself during the second and third week in pig eyes.

Retinal edema in BRVO is caused by leakage of serum from

Dr Ian L. McAllister is an Associate Professor at the Lions Eye Institute in Perth Western, Australia and at the University of Western, Australia. He received his medical degree and post-graduate Ophthalmology training in Perth and completed a vitreo retinal fellowship at the Cleveland Clinic in Ohio. Dr McAllister's academic interests are in the area of retinal vascular disease and age-related macular degeneration. Dr McAllister has published more than 100 peer-reviewed articles and holds

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    Dr Ian L. McAllister is an Associate Professor at the Lions Eye Institute in Perth Western, Australia and at the University of Western, Australia. He received his medical degree and post-graduate Ophthalmology training in Perth and completed a vitreo retinal fellowship at the Cleveland Clinic in Ohio. Dr McAllister's academic interests are in the area of retinal vascular disease and age-related macular degeneration. Dr McAllister has published more than 100 peer-reviewed articles and holds numerous grants including NH&MRC program and project grants.

    Dr Sarojini Vijayasekaran obtained her Master of Medical Science and Doctor of Philosophy degrees from the University of Western Australia. She is currently a Senior Research Officer at the Lions Eye Institute, Perth, Australia. Dr Vijayasekaran contribution to ophthalmology has been in histo-pathology in animal models which includes the development of the ‘Chirila keratoprosthesis’, retinal to choroidal vein by pass and new treatment strategies in retinal vein occlusive diseases. These studies have been published in peer-reviewed journals.

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