Skip to main content
Top
Published in: Journal of Neural Transmission 12/2009

01-12-2009 | Basic Neurosciences, Genetics and Immunology - Original Article

A novel biomarker for retinal degeneration: vitreous body neurofilament proteins

Authors: Axel Petzold, Anselm Junemann, Konrad Rejdak, Tomasz Zarnowski, Sebastian Thaler, Pawel Grieb, Friedrich E. Kruse, Eberhart Zrenner, Robert Rejdak

Published in: Journal of Neural Transmission | Issue 12/2009

Login to get access

Abstract

Retinal degeneration leads to release of cell-type specific proteins into the adjacent compartment. Here we investigated whether the neurofilament heavy chain protein (NfH) could be measured from the vitreous body and anterior chamber fluid. This prospective study included 85 patients who underwent vitrectomy (44 retinal detachment, 12 macular hole, 15 epiretinal gliosis, 8 organ donors) or trabelectomy (six glaucoma). The cut-off level was calculated from the organ donors. An established enzyme-linked immunosorbent assay (ELISA, SMI35) was used for quantification of NfH (190–210 kDa). Measurable levels of NfH were detected from the vitreous body homogenate, but not from the anterior chamber fluid. The cut-off level was 0.29 ng/mL. A significant proportion of patients suffering from retinal detachment (43.2%, mean 0.74 ng/mL) had vitreous body NfH levels above cut-off when compared to organ donors (0%, 0.12 ng/mL, p = 0.02), epiretinal sclerosis (1.6%, 0.05 ng/mL, p = 0.01), macular hole (0%, 0.04 ng/mL, p = 0.004). Following retinal detachment, vitreous NfH-SMI35 levels correlated with time from onset (R = −0.3, p < 0.05), persisting for up to 2 years. This study shows that NfH can be quantified from the human vitreous body and may be a useful novel biomarker for retinal degeneration. The method can be applied for investigating the dynamics of retinal degeneration and the response to neuroprotective strategies in a broad range of retinal diseases in either clinical or experimental research.
Literature
go back to reference Balaratnasingam C, Morgan WH, Bass L, Matich G, Cringle SJ, Yu D (2007) Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure. Invest Ophthalmol Vis Sci 48:3632–3644CrossRefPubMed Balaratnasingam C, Morgan WH, Bass L, Matich G, Cringle SJ, Yu D (2007) Axonal transport and cytoskeletal changes in the laminar regions after elevated intraocular pressure. Invest Ophthalmol Vis Sci 48:3632–3644CrossRefPubMed
go back to reference Balaratnasingam C, Morgan WH, Bass L, Cringle SJ, Yu DY (2008) Time-dependent effects of elevated intraocular pressure on optic nerve head axonal transport and cytoskeleton proteins. Invest Ophthalmol Vis Sci 49:986–999CrossRefPubMed Balaratnasingam C, Morgan WH, Bass L, Cringle SJ, Yu DY (2008) Time-dependent effects of elevated intraocular pressure on optic nerve head axonal transport and cytoskeleton proteins. Invest Ophthalmol Vis Sci 49:986–999CrossRefPubMed
go back to reference Fatt I (1975) Flow and diffusion in the vitreous body of the eye. Bull Math Biol 37:85–90PubMed Fatt I (1975) Flow and diffusion in the vitreous body of the eye. Bull Math Biol 37:85–90PubMed
go back to reference Fowlks WL (1963) Meridional flow from the corona ciliaris through the pararetinal zone of the rabbit vitreous. Invest Ophthal 2:63–71PubMed Fowlks WL (1963) Meridional flow from the corona ciliaris through the pararetinal zone of the rabbit vitreous. Invest Ophthal 2:63–71PubMed
go back to reference Golling M, Kellner H, Fonouni H, Rad MT, Urbaschek R, Breitkreutz R, Gebhard MM, Mehrabi A (2008) Reduced glutathione in the liver as a potential viability marker in non-heart-beating donors. Liver Transpl 14:1637–1647CrossRefPubMed Golling M, Kellner H, Fonouni H, Rad MT, Urbaschek R, Breitkreutz R, Gebhard MM, Mehrabi A (2008) Reduced glutathione in the liver as a potential viability marker in non-heart-beating donors. Liver Transpl 14:1637–1647CrossRefPubMed
go back to reference Groetzner J, Kaczmarek I, Meiser B, Muller M, Daebritz S, Uberfuhr P, Reichart B (2002) The new German allocation system for donated thoracic organs causes longer ischemia and increased costs. Thorac Cardiovasc Surg 50:376–379CrossRefPubMed Groetzner J, Kaczmarek I, Meiser B, Muller M, Daebritz S, Uberfuhr P, Reichart B (2002) The new German allocation system for donated thoracic organs causes longer ischemia and increased costs. Thorac Cardiovasc Surg 50:376–379CrossRefPubMed
go back to reference Hayreh SS (1966) Posterior drainage of the interocular fluid from the vitreous. Exp Eye Res 5:123–144CrossRef Hayreh SS (1966) Posterior drainage of the interocular fluid from the vitreous. Exp Eye Res 5:123–144CrossRef
go back to reference Kashiwagi K, Ou B, Nakamura S et al (2003) Increase in dephosphorylation of the heavy neurofilament subunit in the monkey chronic glaucoma model. Invest Ophthalmol Vis Sci 44(1):154–159CrossRefPubMed Kashiwagi K, Ou B, Nakamura S et al (2003) Increase in dephosphorylation of the heavy neurofilament subunit in the monkey chronic glaucoma model. Invest Ophthalmol Vis Sci 44(1):154–159CrossRefPubMed
go back to reference Kubay OV, Charteris DG, Newland HS, Raymond GL (2005) Retinal detachment neuropathology and potential strategies for neuroprotection. Surv Ophthalmol 50:463–475CrossRefPubMed Kubay OV, Charteris DG, Newland HS, Raymond GL (2005) Retinal detachment neuropathology and potential strategies for neuroprotection. Surv Ophthalmol 50:463–475CrossRefPubMed
go back to reference Maurice DM (1957) The exchange of sodium between the vitreous body and the blood and aqueous humor. J Physiol 137:110–125PubMed Maurice DM (1957) The exchange of sodium between the vitreous body and the blood and aqueous humor. J Physiol 137:110–125PubMed
go back to reference Ou B, Ohno S, Terada N, Fujii Y, Ueda H, Chen HB, Tsukahara S (1997) Ultrastructural study of axonal cytoskeletons in the optic nerve damaged by acutely elevated intraocular pressure using the quick-freezing and deep-etching technique. Ophthalmic Res 29:48–54PubMedCrossRef Ou B, Ohno S, Terada N, Fujii Y, Ueda H, Chen HB, Tsukahara S (1997) Ultrastructural study of axonal cytoskeletons in the optic nerve damaged by acutely elevated intraocular pressure using the quick-freezing and deep-etching technique. Ophthalmic Res 29:48–54PubMedCrossRef
go back to reference Pease ME, McKinnon SJ, Quigley HA, Kerrigan-Baumrind LA, Zack DJ (2000) Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci 41:764–774PubMed Pease ME, McKinnon SJ, Quigley HA, Kerrigan-Baumrind LA, Zack DJ (2000) Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci 41:764–774PubMed
go back to reference Petzold A (2005) Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 233:183–198CrossRefPubMed Petzold A (2005) Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 233:183–198CrossRefPubMed
go back to reference Petzold A, Shaw G (2007) Comparison of two ELISA methods for measuring levels of the phosphorylated neurofilament heavy chain. J Immunol Methods 319:34–40CrossRefPubMed Petzold A, Shaw G (2007) Comparison of two ELISA methods for measuring levels of the phosphorylated neurofilament heavy chain. J Immunol Methods 319:34–40CrossRefPubMed
go back to reference Petzold A, Keir G, Green AJE, Giovannoni G, Thompson EJ (2003) A specific ELISA for measuring neurofilament heavy chain phosphoforms. J Immunol Methods 278:179–190CrossRefPubMed Petzold A, Keir G, Green AJE, Giovannoni G, Thompson EJ (2003) A specific ELISA for measuring neurofilament heavy chain phosphoforms. J Immunol Methods 278:179–190CrossRefPubMed
go back to reference Petzold A, Islam N, Plant GT (2004a) Transient monocular blindness: the controversial role of the ophthalmic artery. J Neurol 250:501–502 Petzold A, Islam N, Plant GT (2004a) Transient monocular blindness: the controversial role of the ophthalmic artery. J Neurol 250:501–502
go back to reference Petzold A, Rejdak K, Plant GT (2004b) Axonal degeneration and inflammation in acute optic neuritis. J Neurol Neurosurg Psychiatry 75:1178–1180CrossRefPubMed Petzold A, Rejdak K, Plant GT (2004b) Axonal degeneration and inflammation in acute optic neuritis. J Neurol Neurosurg Psychiatry 75:1178–1180CrossRefPubMed
go back to reference Shah RB, Yang Y, Khan MA, Faustino PJ (2008) Molecular weight determination for colloidal iron by Taguchi optimized validated gel permeation chromatography. Int J Pharm 353:21–27CrossRefPubMed Shah RB, Yang Y, Khan MA, Faustino PJ (2008) Molecular weight determination for colloidal iron by Taguchi optimized validated gel permeation chromatography. Int J Pharm 353:21–27CrossRefPubMed
go back to reference Shaw G, Yang C, Ellis R, Anderson K et al (2005) Hyperphosphorylated neurofilament NF-H is a serum biomarker for axonal injury. Biochem Biophys Res Comm 336:1268–1277CrossRefPubMed Shaw G, Yang C, Ellis R, Anderson K et al (2005) Hyperphosphorylated neurofilament NF-H is a serum biomarker for axonal injury. Biochem Biophys Res Comm 336:1268–1277CrossRefPubMed
go back to reference Shaw G (1998) Neurofilaments. Springer-Verlag. ISBN: 3-540-64715-5 Shaw G (1998) Neurofilaments. Springer-Verlag. ISBN: 3-540-64715-5
go back to reference Teunissen CE, Dijkstra C, Polman C (2005) Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol 4:32–41CrossRefPubMed Teunissen CE, Dijkstra C, Polman C (2005) Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol 4:32–41CrossRefPubMed
go back to reference Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Veeranna, Liem RK, Eyer J, Peterson AC, Julien JP, Nixon RA (2006) Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci 26:10006–10019 Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Veeranna, Liem RK, Eyer J, Peterson AC, Julien JP, Nixon RA (2006) Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci 26:10006–10019
Metadata
Title
A novel biomarker for retinal degeneration: vitreous body neurofilament proteins
Authors
Axel Petzold
Anselm Junemann
Konrad Rejdak
Tomasz Zarnowski
Sebastian Thaler
Pawel Grieb
Friedrich E. Kruse
Eberhart Zrenner
Robert Rejdak
Publication date
01-12-2009
Publisher
Springer Vienna
Published in
Journal of Neural Transmission / Issue 12/2009
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-009-0316-8

Other articles of this Issue 12/2009

Journal of Neural Transmission 12/2009 Go to the issue

Biological Child and Adolescent Psychiatry - Original Article

Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood ADHD