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S. K. McRee, B. Tucker, M. J. Bradbury, M. Young, G. Velez; Indocyanine Green (ICG) Induces Increased Müller Cell Expression of Adhesion Molecules and Membrane Metalloproteinases in vitro. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5762.
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ICG is a protein often used during vitreoretinal surgical procedures to help visualize the internal limiting membrane (ILM). It has been shown in previous studies to induce apoptosis in vitro in Müller cells. The bcl-2 and caspase cascades have been suggested as possible pathways. However, Müller cells have also been shown to be stimulated in the context of retinal injury. This has been observed in animal models of both laser injury and retinal detachment. We explore the effect of ICG on Müller cells in vitro, and whether it can have a protracted and lasting stimulatory effect on these cells.
Human Müller cells (MIO-M1) were exposed to clinical doses of ICG (2.5mg/ml) for 10 min, then thoroughly washed with PBS. Cells were harvested for lysate preparation immediately, 24 hrs, 48 hrs, and 72 hrs after exposure. Lysates were then analyzed by Western blotting for expression of the Integrins β1, α3, and α5, as well as MMP1, MMP2 and TIMP-1.
An acute increase in Integrin β1, Integrin α3, Integrin α5, MMP1, MMP2 and TIMP-1 was noted immediately after exposure to ICG. 24 hrs after exposure there was a sustained increase in expression when compared to control with a decrease when compared to expression immediately after exposure to ICG. 48 and 72 hrs after exposure, there was a sustained increase in expression above control and 24 hr levels.
Our results suggest that the injury exerted by ICG on Müller cells has a sustained proliferative effect. This alteration in Müller cell behavior could lead to an increased gliotic response which could be beneficial in certain clinical situations (macular hole closure) but potentially detrimental in others.
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