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104. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft 2006
Abstract
Abstract
FR.11.05 How to measure neuroprotection – possible surrogate marker for neurodegeneration Rejdak R.1,4,5, Petzold A.2, Rejdak K.3, Zarnowski T.4, Mankowska A.4, Zagorski Z.4, Kruse F.1, Zrenner E.5, Junemann A.1
1Department of Ophthalmology, University of Erlangen–Nurnberg, Germany; 2Department of Neuroimmunology, Institute of Neurology, Queen Square, London; UK; 3Department of Neurology, Medical University of Lublin, Poland; 41st Eye Hospital, Medical University of Lublin, Poland; 5Department of Ophthalmology, University of Tuebingen, Germany Degeneration of retinal axons, clinically observed as thinning of the nerve fibre layer, is associated permanent loss of vision. In many common diseases such as glaucoma, diabetic retinopathy, the functional damage may start with a small visual field defect which can progress to partial or complete blindness over time.
Over the last decades several models have been developed to study the loss of retinal axons and their ganglion cells (RGC) experimentally. With the emergence of new neuroprotective compounds these models are needed to address adequately those issues of high relevance for future clinical trials.
Biomarkers are an attractive tool for quantifying neurodegeneration. Neurofilaments can be used to specifically measure neuro-axonal loss because they are generally not expressed in other cell-types. For this reason a semi-quantitative method based RT-PCR of the mRNA of the neurofilament light chain (NfL) has been developed. This approach is logical because the amount of mRNA from the retinal tissue homogenate is likely to correlate with the number of RGC.
Our approach is based on direct quantification of a biomarker for axonal loss from the anterior chamber fluid and the vitreous body using a high throughput quantitative approach. Because of its relative biological stability and the availability of an ELISA, the phosphorylated form of the neurofilament heavy chain was the chosen biomarker.
Here we show for the first time that NfHSMI35 can be quantified from the vitreous body, but not from the anterior chamber fluid in humans. We also investigate whether the phosphorylated form of the neurofilament heavy chain (NfHSMI35), an important biomarker for axonal degeneration, could be measured from a fluid compartment of the eye.
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