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S. Hayes, K. Lieu, C. Bavik, R. Kubota; OcuScreenTM, ex vivo Screen, for Drug Discovery and Detection of Retinal Toxins. Invest. Ophthalmol. Vis. Sci. 2009;50(13):678.
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Acucela has developed assays which utilize long-lived, fully-differentiated primary retinal neurons for ex vivo screening. These screens referred to as OcuScreenTM, have been developed for: drug discovery and detection of retinal toxins. Novel drugs are needed for blinding disorders; age-related macular degeneration (AMD) is the major cause of blindness in adults and there are no therapeutics available to treat the dry form of AMD. With OcuScreenTM, primary mixed retinal cell cultures can be stressed in physiologically relevant ways that recapitulate neurodeterioration seen in blinding eye diseases such as age related macular degeneration, we can therefore screen for compounds that protect against such stresses. OcuScreenTM has also been developed to determine retinal toxicity. Retinal toxins are found in industrial compounds, pollutants, and pharmaceuticals, but predicting risk of exposure is challenging. Exposure to these toxins is a risk factor in retinal degeneration, which can eventually lead to blindness. Currently, retinal toxicity is assessed using in vivo assays, which require large numbers of animals, are time-consuming and expensive. With OcuScreenTM, Acucela is able to determine retinal toxicity using few animals, quickly, and affordably.
In Vitro Assays: Primary retinal cultures were treated. Cell death was quantitated by Sytox assay (Molecular Probes). Sometimes, cultures were stained and specific retinal cell types were counted.In Vivo Assays: Mice were treated with test compound before exposure to light. Retinas were analyzed with the Cell Death ELISA (Roche Molecular Biochemicals).
We identified neuroprotective compounds that work in vitro and in vivo. The toxicity assay correctly identified most of the retinal toxins.
OcuScreenTM, was able to identify compounds that are neuroprotective against oxidative and light damage both in vitro and in vivo. These compounds may serve as leads for new drugs. The toxicity assay may serve as a first pass assay prior to in vivo studies when evaluating retinal toxicity.
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