Lack of immunoglobulins does not prevent C1q binding to RGC and does not alter the progression of experimental glaucoma

Qiong J Ding; Amy C Cook; Alina V Dumitrescu; Markus H Kuehn

doi:10.1167/iovs.12-10442

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Lack of immunoglobulins does not prevent C1q binding to RGC and does not alter the progression of experimental glaucoma

Journal article

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Peer reviewed

Lack of immunoglobulins does not prevent C1q binding to RGC and does not alter the progression of experimental glaucoma

Qiong J Ding, Amy C Cook, Alina V Dumitrescu and Markus H Kuehn

Investigative ophthalmology & visual science, Vol.53(10), pp.6370-6377

09/19/2012

DOI: 10.1167/iovs.12-10442

PMCID: PMC3465017

PMID: 22918632

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Abstract

The degeneration of retinal ganglion cells (RGC) in the glaucomatous retina is accompanied by activation of the classical complement cascade. The purpose of this study was to evaluate whether complement component C1q binding and activation of the complement cascade in the glaucomatous retina requires the presence of immunoglobulins. Experimental glaucoma was induced in normal mice and those carrying a targeted deletion of the RAG1 gene. Binding of C1q to RGC and accumulation of C3 and C5b-9 was investigated using immunohistochemical and proteomic approaches. Damage to the optic nerve and RGC was determined and compared between the two strains. Complement activation and accumulation were also evaluated in vitro using dissociated retinal cell cultures. C1q was detected in the RGC layer in both RAG1(-/-) and control mice with elevated IOP, but not in mice with normal IOP. Proteomic analysis of retinal membrane fractions indicated that C1q and C3 are membrane bound to a similar degree in RAG1(-/-) and control mice with elevated IOP. The absence of Ig does not affect the rate of axonal damage or RGC loss. Furthermore, cultured RGC maintained in serum-free media are also C1q and C3 immunoreactive, demonstrating that Ig is not required for C1q binding to damaged RGC. Our data demonstrate that lack of immunoglobulins and mature T/B cells does not influence the progression of glaucoma. Furthermore, immunoglobulins do not appear to be required for C1q binding and complement cascade activation on damaged RGC. These findings suggest that C1q recognizes an alternative binding partner expressed by stressed RGC.

Immunohistochemistry

Optic Nerve - pathology

Immunoglobulins - immunology

Complement C1q - immunology

Retinal Ganglion Cells - metabolism

Complement C1q - metabolism

Retinal Ganglion Cells - pathology

Immunoglobulins - metabolism

Mice, Mutant Strains

Optic Nerve - immunology

Glaucoma - metabolism

Immunologic Deficiency Syndromes - immunology

Disease Models, Animal

Complement C3 - metabolism

Mice, Inbred C57BL

Cells, Cultured

Retinal Ganglion Cells - immunology

Disease Progression

Homeodomain Proteins - genetics

Complement C3 - immunology

Intraocular Pressure - immunology

Animals

Proteomics

Glaucoma - immunology

Immunologic Deficiency Syndromes - metabolism

Mice

Optic Nerve - metabolism

Details

Title: Subtitle: Lack of immunoglobulins does not prevent C1q binding to RGC and does not alter the progression of experimental glaucoma
Creators: Qiong J Ding - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa 52242, USA
Amy C Cook
Alina V Dumitrescu
Markus H Kuehn
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.53(10), pp.6370-6377
Publisher: United States
DOI: 10.1167/iovs.12-10442
PMID: 22918632
PMCID: PMC3465017
ISSN: 0146-0404
eISSN: 1552-5783
Grant note: R01 EY019485 / NEI NIH HHS EY019485 / NEI NIH HHS
Language: English
Date published: 09/19/2012
Academic Unit: Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences
Record Identifier: 9983979994302771

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