Expression of multiple forms of clusterin during light-induced retinal degeneration

P. Wong Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

T. Ulyanova Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

D.T. Organisciak Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

S. Bennett Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

J. Lakins Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

J.M. Arnold Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

R.K. Kutty Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

M. Tenniswood Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

T. vanVeen Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

R.M. Darrow Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

G. Chader Department of Biological Sciences, University of Alberta, Edmonton, Canada; Department of Pathology, Washington University, St. Louis, MO, USA; Petticrew Research Laboratory, Departments of Biochemistry and Molecular Biology and Ophthalmology, Wright State University, Dayton, OH, USA; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA; Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Canada; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD, USA; 8Department of Ophthalmology, Lund University Hospital, Lund, Sweden; 9National Retinitis Pigmentosa Inc., Hunt Valley, MD, USA Both authors contributed equally to the work presented and share first authorship.

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Abstract

Purpose. Clusterin has been associated with active cell death in several different model systems, including animal models of retinal degeneration. Clusterin is also expressed in normal tissues, a finding that leads to the question of how it could then play a cell death-specific role during tissue regression. To address this paradox, we have examined clusterin expression during light-induced retinal damage in rats. Methods. Normal albino rats were reared in darkness and then exposed to intense visible light to induce retinal degeneration. Clusterin expression was then examined at various times after light treatment. Standard molecular techniques including Northern analysis, immunohistochemistry, and Western analysis were employed. Results. Northern analysis established that the largest increase in clusterin expression occurs after a decrease in interphotoreceptor retinoid binding protein, IRBP, expression (an indication of a photoreceptor cell dysfunction) and after an increase in heme oxygenase 1, HO-1, expression (an oxidative stress inducible gene), suggesting that induction of clusterin expression is an oxidative stress response. Immunohistochemical analysis with two different clusterin-specific antibodies, anti(SGP-2) and anti(301), localized distinct forms of clusterin to Müller cells and degenerating photo-receptor cells. Western analysis demonstrated degeneration associated isoforms of clusterin in light treated retina that are not present in normal retina. Conclusion. Clusterin over-expression is characteristic of a retinal degeneration phenotype and we propose that clusterin action may be defined by the nature in which it is modified. We hypothesize that alternate processing leads to retinal degeneration-specific forms of the protein (65, 61, and 50 kDa) that are not present in normal retina.

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Expression of multiple forms of clusterin during light-induced retinal degeneration

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Expression of multiple forms of clusterin during light-induced retinal degeneration

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