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Fcy receptor upregulation is associated with immune complex inflammation in the mouse retina and early age-related macular degeneration

Fcy receptor upregulation is associated with immune complex inflammation in the mouse retina and early age-related macular degeneration
Fcy receptor upregulation is associated with immune complex inflammation in the mouse retina and early age-related macular degeneration
Purpose: Several lines of evidence suggest the involvement of antibodies and immune complex inflammation in AMD, a blinding disease with a strong inflammatory component. To examine this further, we developed a novel experimental mouse model of retinal inflammation and evaluated whether inflammation associated with immune complex formation was present in eyes of AMD donors.

Methods: A localized immune complex-mediated reaction was induced in the retina of wild-type (WT), Fc receptor ? chain-deficient (?(-/-)), and C1q-deficient (C1q(-/-)) mice, and donor eyes were obtained after death from donors with early or wet AMD and from healthy control subjects. The presence of immune complexes, Fc? receptors (Fc?Rs), and markers of macrophage/microglia activation was investigated by immunohistochemistry.

Results: In WT and C1q(-/-) mice, immune complex deposition in the retina led to a robust inflammatory response with activation of microglia, recruitment of myeloid cells, and increased expression of Fc?RI through Fc?RIV and major histocompatibility complex class II. This response was not observed in ?(-/-) mice lacking activating Fc?Rs. We found that early AMD was associated with deposition of IgG, C1q, and membrane attack complex in the choriocapillaris and with increased numbers of CD45+ cells expressing Fc?RIIa and Fc?RIIb. Furthermore, Fc?RIIa and Fc?RIIb were observed in eyes of donors with wet AMD.

Conclusions: Our studies suggest that immune complexes may contribute to AMD pathogenesis through interaction of IgG with Fc?Rs and might inform about possible adverse effects associated with therapeutic antibodies
fc receptor, immune complex, immunoglobulin, inflammation, macular degeneration
0146-0404
247-258
Murinello, S.
6fb1c1a2-5e36-4664-9fb4-a070ad74d88b
Mullins, R.F.
467f59d5-f246-4698-8de0-c337644e2e2e
Lotery, A.J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Murinello, S.
6fb1c1a2-5e36-4664-9fb4-a070ad74d88b
Mullins, R.F.
467f59d5-f246-4698-8de0-c337644e2e2e
Lotery, A.J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a

Murinello, S., Mullins, R.F., Lotery, A.J., Perry, V.H. and Teeling, Jessica L. (2014) Fcy receptor upregulation is associated with immune complex inflammation in the mouse retina and early age-related macular degeneration. Investigative Ophthalmology & Visual Science, 55 (1), 247-258. (doi:10.1167/iovs.13-11821). (PMID:24334446)

Record type: Article

Abstract

Purpose: Several lines of evidence suggest the involvement of antibodies and immune complex inflammation in AMD, a blinding disease with a strong inflammatory component. To examine this further, we developed a novel experimental mouse model of retinal inflammation and evaluated whether inflammation associated with immune complex formation was present in eyes of AMD donors.

Methods: A localized immune complex-mediated reaction was induced in the retina of wild-type (WT), Fc receptor ? chain-deficient (?(-/-)), and C1q-deficient (C1q(-/-)) mice, and donor eyes were obtained after death from donors with early or wet AMD and from healthy control subjects. The presence of immune complexes, Fc? receptors (Fc?Rs), and markers of macrophage/microglia activation was investigated by immunohistochemistry.

Results: In WT and C1q(-/-) mice, immune complex deposition in the retina led to a robust inflammatory response with activation of microglia, recruitment of myeloid cells, and increased expression of Fc?RI through Fc?RIV and major histocompatibility complex class II. This response was not observed in ?(-/-) mice lacking activating Fc?Rs. We found that early AMD was associated with deposition of IgG, C1q, and membrane attack complex in the choriocapillaris and with increased numbers of CD45+ cells expressing Fc?RIIa and Fc?RIIb. Furthermore, Fc?RIIa and Fc?RIIb were observed in eyes of donors with wet AMD.

Conclusions: Our studies suggest that immune complexes may contribute to AMD pathogenesis through interaction of IgG with Fc?Rs and might inform about possible adverse effects associated with therapeutic antibodies

Full text not available from this repository.

More information

Accepted/In Press date: 2 December 2013
e-pub ahead of print date: 13 January 2014
Published date: 13 January 2014
Keywords: fc receptor, immune complex, immunoglobulin, inflammation, macular degeneration
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 367810
URI: https://eprints.soton.ac.uk/id/eprint/367810
ISSN: 0146-0404
PURE UUID: 612a69b7-a440-477e-9f46-a6fbc0ff9dcd
ORCID for A.J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Jessica L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391

Catalogue record

Date deposited: 18 Aug 2014 10:31
Last modified: 20 Jul 2019 01:01

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