Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion

Hengwei Liu; Yufan Zhou; Jinyan Qi; Shengnan Liang; Tingting Guo; Juan Chen; Huanhuan Tan; Jie Wang; Heping Xu; Zhongping Chen

doi:10.1186/s12886-024-03781-3

Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion

Hengwei Liu, Yufan Zhou, Jinyan Qi, Shengnan Liang, Tingting Guo, Juan Chen, Huanhuan Tan, Jie Wang, Heping Xu^*, Zhongping Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background
Retinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies.

Methods
The plasma and aqueous humour were collected from 20 treatment-naive RVO and 20 cataract patients. Retinal lesions were examined by fundus stereoscopy and optical coherence tomography angiography. The levels of C1q, C2, C4, C4b, C3, C3b/iC3b, C5, C5a, CFB, CFD, CFI, CFH, and MBL in the plasma and aqueous humour were measured using the Luminex® x MAP® multiplex assay.

Results
RVO patients had significantly higher levels of C4, C4b, C3b/iC3b, CFB, and CFH in the plasma and aqueous humour compared to controls. The aqueous levels of C1q, C2, C5, C5a, and MBL were also significantly higher in RVO patients than in controls. CRVO patients had higher intraocular levels of C1q, C4, C5, CFI, CFH, and MBL than BRVO patients. C5a was below the detectable limit in the plasma in 18 cataracts and 16 RVO participants. The intraocular levels of C5a positively correlated with C1q, C2, C4, C3, C5, CFB, CFH, and MBL. The intraocular levels of CFD, CFI and MBL positively correlated with CRT, and the levels of C2, C3, C5, CFB, and MBL negatively correlated with the size of the foveal avascular zone. The plasma levels of C4b, C3b/iC3b, and CFD positively correlated with their counterparts in the aqueous humour in cataracts but not in RVO patients. The ratios of aqueous humour/plasma of C1q, C4, C4b, C3b/iC3b, C5, CFB, CFD, CFI, and CFH in the RVO patients were significantly higher than those in the cataract patients.

Discussion and conclusions
The intraocular complement activation in RVO is mediated by the classical and the alternative pathways and is largely independent of systemic complement activation. Intraocular complement activation may be related to retinal oedema and vascular remodeling in RVO patients.

Original language	English
Article number	509
Number of pages	10
Journal	BMC Ophthalmology
Volume	24
DOIs	https://doi.org/10.1186/s12886-024-03781-3
Publication status	Published - 25 Nov 2024

Keywords

aged
aged, 80 and over
aqueous humor
vascular remodeling
biomarkers
classical pathway
complement activation
complement proteins
complement system proteins
female
Fluorescein angiography
humans
macula lutea
male
middle aged
optical coherence tomographic angiography
Retinal vein occlusion

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Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion
Copyright 2024 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.17 MBLicence: CC BY

Cite this

@article{64572053616a4059b64d2db8fde9a8e7,

title = "Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion",

abstract = "BackgroundRetinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies.MethodsThe plasma and aqueous humour were collected from 20 treatment-naive RVO and 20 cataract patients. Retinal lesions were examined by fundus stereoscopy and optical coherence tomography angiography. The levels of C1q, C2, C4, C4b, C3, C3b/iC3b, C5, C5a, CFB, CFD, CFI, CFH, and MBL in the plasma and aqueous humour were measured using the Luminex{\textregistered} x MAP{\textregistered} multiplex assay.ResultsRVO patients had significantly higher levels of C4, C4b, C3b/iC3b, CFB, and CFH in the plasma and aqueous humour compared to controls. The aqueous levels of C1q, C2, C5, C5a, and MBL were also significantly higher in RVO patients than in controls. CRVO patients had higher intraocular levels of C1q, C4, C5, CFI, CFH, and MBL than BRVO patients. C5a was below the detectable limit in the plasma in 18 cataracts and 16 RVO participants. The intraocular levels of C5a positively correlated with C1q, C2, C4, C3, C5, CFB, CFH, and MBL. The intraocular levels of CFD, CFI and MBL positively correlated with CRT, and the levels of C2, C3, C5, CFB, and MBL negatively correlated with the size of the foveal avascular zone. The plasma levels of C4b, C3b/iC3b, and CFD positively correlated with their counterparts in the aqueous humour in cataracts but not in RVO patients. The ratios of aqueous humour/plasma of C1q, C4, C4b, C3b/iC3b, C5, CFB, CFD, CFI, and CFH in the RVO patients were significantly higher than those in the cataract patients.Discussion and conclusionsThe intraocular complement activation in RVO is mediated by the classical and the alternative pathways and is largely independent of systemic complement activation. Intraocular complement activation may be related to retinal oedema and vascular remodeling in RVO patients.",

keywords = "aged, aged, 80 and over, aqueous humor, vascular remodeling, biomarkers, classical pathway, complement activation, complement proteins, complement system proteins, female, Fluorescein angiography, humans, macula lutea, male, middle aged, optical coherence tomographic angiography, Retinal vein occlusion",

author = "Hengwei Liu and Yufan Zhou and Jinyan Qi and Shengnan Liang and Tingting Guo and Juan Chen and Huanhuan Tan and Jie Wang and Heping Xu and Zhongping Chen",

year = "2024",

month = nov,

day = "25",

doi = "10.1186/s12886-024-03781-3",

language = "English",

volume = "24",

journal = "BMC Ophthalmology",

issn = "1471-2415",

publisher = "BioMed Central",

}

TY - JOUR

T1 - Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion

AU - Liu, Hengwei

AU - Zhou, Yufan

AU - Qi, Jinyan

AU - Liang, Shengnan

AU - Guo, Tingting

AU - Chen, Juan

AU - Tan, Huanhuan

AU - Wang, Jie

AU - Xu, Heping

AU - Chen, Zhongping

PY - 2024/11/25

Y1 - 2024/11/25

N2 - BackgroundRetinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies.MethodsThe plasma and aqueous humour were collected from 20 treatment-naive RVO and 20 cataract patients. Retinal lesions were examined by fundus stereoscopy and optical coherence tomography angiography. The levels of C1q, C2, C4, C4b, C3, C3b/iC3b, C5, C5a, CFB, CFD, CFI, CFH, and MBL in the plasma and aqueous humour were measured using the Luminex® x MAP® multiplex assay.ResultsRVO patients had significantly higher levels of C4, C4b, C3b/iC3b, CFB, and CFH in the plasma and aqueous humour compared to controls. The aqueous levels of C1q, C2, C5, C5a, and MBL were also significantly higher in RVO patients than in controls. CRVO patients had higher intraocular levels of C1q, C4, C5, CFI, CFH, and MBL than BRVO patients. C5a was below the detectable limit in the plasma in 18 cataracts and 16 RVO participants. The intraocular levels of C5a positively correlated with C1q, C2, C4, C3, C5, CFB, CFH, and MBL. The intraocular levels of CFD, CFI and MBL positively correlated with CRT, and the levels of C2, C3, C5, CFB, and MBL negatively correlated with the size of the foveal avascular zone. The plasma levels of C4b, C3b/iC3b, and CFD positively correlated with their counterparts in the aqueous humour in cataracts but not in RVO patients. The ratios of aqueous humour/plasma of C1q, C4, C4b, C3b/iC3b, C5, CFB, CFD, CFI, and CFH in the RVO patients were significantly higher than those in the cataract patients.Discussion and conclusionsThe intraocular complement activation in RVO is mediated by the classical and the alternative pathways and is largely independent of systemic complement activation. Intraocular complement activation may be related to retinal oedema and vascular remodeling in RVO patients.

AB - BackgroundRetinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies.MethodsThe plasma and aqueous humour were collected from 20 treatment-naive RVO and 20 cataract patients. Retinal lesions were examined by fundus stereoscopy and optical coherence tomography angiography. The levels of C1q, C2, C4, C4b, C3, C3b/iC3b, C5, C5a, CFB, CFD, CFI, CFH, and MBL in the plasma and aqueous humour were measured using the Luminex® x MAP® multiplex assay.ResultsRVO patients had significantly higher levels of C4, C4b, C3b/iC3b, CFB, and CFH in the plasma and aqueous humour compared to controls. The aqueous levels of C1q, C2, C5, C5a, and MBL were also significantly higher in RVO patients than in controls. CRVO patients had higher intraocular levels of C1q, C4, C5, CFI, CFH, and MBL than BRVO patients. C5a was below the detectable limit in the plasma in 18 cataracts and 16 RVO participants. The intraocular levels of C5a positively correlated with C1q, C2, C4, C3, C5, CFB, CFH, and MBL. The intraocular levels of CFD, CFI and MBL positively correlated with CRT, and the levels of C2, C3, C5, CFB, and MBL negatively correlated with the size of the foveal avascular zone. The plasma levels of C4b, C3b/iC3b, and CFD positively correlated with their counterparts in the aqueous humour in cataracts but not in RVO patients. The ratios of aqueous humour/plasma of C1q, C4, C4b, C3b/iC3b, C5, CFB, CFD, CFI, and CFH in the RVO patients were significantly higher than those in the cataract patients.Discussion and conclusionsThe intraocular complement activation in RVO is mediated by the classical and the alternative pathways and is largely independent of systemic complement activation. Intraocular complement activation may be related to retinal oedema and vascular remodeling in RVO patients.

KW - aged

KW - aged, 80 and over

KW - aqueous humor

KW - vascular remodeling

KW - biomarkers

KW - classical pathway

KW - complement activation

KW - complement proteins

KW - complement system proteins

KW - female

KW - Fluorescein angiography

KW - humans

KW - macula lutea

KW - male

KW - middle aged

KW - optical coherence tomographic angiography

KW - Retinal vein occlusion

U2 - 10.1186/s12886-024-03781-3

DO - 10.1186/s12886-024-03781-3

M3 - Article

C2 - 39587546

SN - 1471-2415

VL - 24

JO - BMC Ophthalmology

JF - BMC Ophthalmology

M1 - 509

ER -

Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion

Abstract

Keywords

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