Abstract

FR.14.03

Mechanisms of the edema-resolving effect of triamcinolone acetonide in the diabetic retina

Wiedemann P.
Department of Ophthalmology and Eye Clinic, University of Leipzig, Leipzig

Objective: Diabetic retinopathy is the leading cause of acquired blindness in working age adults. One main cause for the vision loss in diabetes is the presence of a macular edema. Diabetic alterations of the microvasculature cause ischemic and inflammatory conditions resulting in breakdown of the blood-retinal barrier and vascular leakage. A second cause of edema is an impairment of the fluid absorption from the retinal tissue normally carried out by Müller glial and pigment epithelial cells which may be associated with cellular swelling (cytotoxic edema). We investigated the effect of triamcinolone acetonide on the secretion of vascular endothelial growth factor (VEGF; the major factor that causes vascular leakage) by pigment epithelial cells, and on the osmotic swelling of Müller cells.
Methods: Secretion of VEGF was determined in cultured human pigment epithelial cells. Swelling of Müller cells in response to hypotonic stress was recorded in retinal slices from diabetic rats.
Results: Triamcinolone reduces strongly the secretion of VEGF by pigment epithelial cells at control conditions and during stimulation with the matrix metalloproteinase-9. Triamcinolone inhibits the osmotic swelling of Müller cells through activation of a purinergic signaling cascade. Triamcinolone induces the release of adenosine from Müller cells which activates A1 receptors. Receptor activation causes the opening of ion channels in the Müller cell membrane. The efflux of ions is associated with a water efflux resulting in inhibition of swelling.
Conclusions: Triamcinolone may resolve diabetic macular edema by both reduction of vascular leakage and inhibition of cytotoxic edema. Adenosine A1 receptors may represent a promising target for the development of novel drugs that stimulate the absorption of edema fluid.

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