Cited by 659Retinal Diseases and TreatmentsOcular Diseases and Behçet’s SyndromeNeuroinflammation and Neurodegeneration Mechanisms

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Para-inflammation in the aging retina

Xu, Heping, Chen, Mei, Forrester, John V.·2009·Progress in Retinal and Eye Research

DOI 10.1016/j.preteyeres.2009.06.001

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Abstract

Para-inflammation is a tissue adaptive response to noxious stress or malfunction and has characteristics that are intermediate between basal and inflammatory states (Medzhitov, 2008). The physiological purpose of para-inflammation is to restore tissue functionality and homeostasis. Para-inflammation may become chronic or turn into inflammation if tissue stress or malfunction persists for a sustained period. Chronic para-inflammation contributes to the initiation and progression of many human diseases including obesity, type 2 diabetes, atherosclerosis, and age-related neurodegenerative diseases. Evidence from our studies and the studies of some others suggests that para-inflammation also exists in the aging retina in physiological conditions and might contribute to age-related retinal pathologies. The purpose of this review is to introduce the notion of "para-inflammation" as a state between frank, overt destructive inflammation and the non-inflammatory removal of dead or dying cells by apoptosis, to the retinal community. In diabetes and atherosclerosis, leukocytes particularly monocytes and vascular endothelial cells are constantly under noxious stress due to glycaemic and/or lipidaemic dysregulation. These blood-borne stresses trigger para-inflammatory responses in leukocytes and endothelial cells by up-regulating the expression of adhesion molecules or releasing cytokines/chemokines, which in turn cause abnormal leukocyte-endothelial interactions and ultimately vascular damage. In the aging retina, on the other hand, oxidized lipoproteins and free radicals are considered to be major causes of tissue stress and serve as local triggers for retinal para-inflammation. Microarray analysis has revealed the up-regulation of a large number of inflammatory genes, including genes involved in complement activation and inflammatory cytokine/chemokine production, in the aging retina. Para-inflammatory responses in the neuroretina of aged mice are characterized by microglial activation and subretinal migration, and breakdown of blood-retinal barrier. At the retinal/choroidal interface para-inflammation is manifested by complement activation in Bruch's membrane and RPE cells, and microglia accumulation in subretinal space. With age, para-inflammatory changes have also been observed in the choroidal tissue, evidenced by 1) increased thickness of choroid; 2) increased number of CD45(+)CRIg(+) macrophages; 3) morphological abnormalities in choroidal melanocytes; and 4) fibrosis in choroidal tissue. An increased knowledge of contribution of retinal para-inflammation to various pathological conditions is essential for the better understanding of the pathogenesis of various age-related retinal diseases including diabetic retinopathy, glaucoma and age-related macular degeneration.

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Background

See all 659

Authors: Xu, H., Chen, M., & Forrester, J. V.
Affiliations: University of Aberdeen (GB)
Corresponding author: Xu, Heping
ORCID: Xu, Heping
Chen, Mei
Forrester, John V.
Venue: Progress in Retinal and Eye Research
Publisher: Elsevier BV
Published: 2009-09
Volume: 28
Issue: 5
Pages: 348-368
ISSN: 1350-9462 (ISSN-L)
DOI: 10.1016/j.preteyeres.2009.06.001
OpenAlex: W2034060753
Cited by: 659
References: 276
Citations by year: 2026: 23 · 2025: 22 · 2024: 44 · 2023: 41 · 2022: 39 · 2021: 54 · 2020: 43 · 2019: 30 · 2018: 44 · 2017: 45 · 2016: 38 · 2015: 56 · 2014: 42 · 2013: 42 · 2012: 42
FWCI: 6.22
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Retinal and Eye Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: microglial activation, complement activation, blood-retinal barrier breakdown, choroid, retinal pigment epithelium, Bruch's membrane, oxidative stress, oxidized lipoproteins, diabetic retinopathy, glaucoma, choroidal neovascularization
MeSH terms: Aging, Animals, Blood-Retinal Barrier, Diabetic Retinopathy, Glaucoma, Humans, Inflammation, Macular Degeneration, Retina, Retinitis, Up-Regulation, Oxidative Stress

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Para-inflammation in the aging retina

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