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Para-inflammation in the aging retina
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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“While the immune tolerance mechanism tries to counterbalance inflammation, danger signals in the retina may still result in mild activation of the innate immune system, in a process recently termed para-inflammation [27][28][29].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [28]
In the citing paper
“In AMD, the oxidative stress may elicit a response also known as “para-inflammation” where the innate immune system induces a mild inflammatory response to restore homeostasis that, if chronic, may contribute to AMD through imbalanced inflammatory response [28].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [28]
In the citing paper
“Retinal inflammation and degeneration have been reported to commence earlier than 24 months in rodents”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [129]
Citations
Cites
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567
The number of people with glaucoma worldwide in 2010 and 2020
Quigley, H. A. (2006) · British Journal of Ophthalmology · doi:10.1136/bjo.2005.081224 · Cited by 7,417
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov, R., Preston-Hurlburt, P., & Janeway, C. A. J. (1997) · Nature · doi:10.1038/41131 · Cited by 6,137
Complement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492
Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1112 · Cited by 3,166 · cited 1×
“Uptake of apoptotic cells by phagocytes induces anti-inflammatory responses, including the production of transforming growth factor b (TGF-b) and interleukin-10 production (Fadok et al., 1998a,b; Voll et al., 1997).”
BackgroundBiology of disease: free radicals and tissue injury.
Freeman, B. Α., & Jd, C. (1982) · PubMed · Cited by 3,038
Prevalence of Age-Related Macular Degeneration in the United States
The Eye Diseases Prevalence Research Group* (2004) · Archives of Ophthalmology · doi:10.1001/archopht.122.4.564 · Cited by 2,774
Signaling to NF-κB by Toll-like receptors
Kawai, T., & Akira, S. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.09.002 · Cited by 2,468
Cited by
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Lem, D. W., Gierhart, D. L., & Davey, P. G. (2021) · Nutrients · doi:10.3390/nu13061949 · Cited by 35
“Persistent overwhelming oxidative insult can trigger immunostimulatory activation of the innate immune system, causing a concurrent low-grade inflammatory response in the retina involving resident immune cells [19,79,80].”
BackgroundThe retinal pigment epithelium as a gateway for monocyte trafficking into the eye
Benhar, I., Reemst, K., Kalchenko, V., & Schwartz, M. (2016) · The EMBO Journal · doi:10.15252/embj.201694202 · Cited by 31
“The accumulation of macrophages in the SRS is reported to increase with age and in the context of retinal disease, such as age-related macular degeneration (AMD), apparently in association with defective immunomodulation by the RPE (Forrester, 2003; Xu et al , 2009; Sennlaub et al , 2013).”
Development of Stem Cell Therapies for Retinal DegenerationPreprint
West, E. L., Ribeiro, J., & Ali, R. R. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035683 · Cited by 32
Subhi, Y., Nielsen, M. K., Molbech, C. R., Oishi, A., Singh, A., Nissen, M. H., & Sørensen, T. L. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22479 · Cited by 30
“As the resident phagocytes of the retina, the microglia increases their activity but may fail to keep up with the increasing phagocytic demand and retinal stress with age.(43,44) This leads to an environment where circulating monocytes are increasingly recruited and macrophages accumulate in the retina to keep up with…”
BackgroundChen, M., Obasanmi, G., Armstrong, D., Lavery, N.-J., Kissenpfennig, A., Lois, N., & Xu, H. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1533-1 · Cited by 30
Self-citationLi, Y., Li, X., Li, X., Zeng, Z., Strang, N. C., Shu, X., & Tan, Z. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114531 · Cited by 30
Khan, A. H., Chowers, I., & Lotery, A. J. (2023) · Cells · doi:10.3390/cells12131708 · Cited by 31
“Similarly, during aging and in the pathogenesis of AMD, accumulation of microglia in the sub-retinal space and inflammatory activation of retinal microglia can also result in disruption of the eye’s immune privilege and production of retinal autoantibodies [70].”
BackgroundASK1 modulates the expression of microRNA Let7A in microglia under high glucose in vitro condition
Song, J., & Lee, J. E. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00198 · Cited by 30
“Microglia activation is linked to changes in both their morphology, including cell hypertrophy (Tsuda et al., 2008), and their function (Wodarski et al., 2009; Xu et al., 2009).”
BackgroundZhang, H., Yang, Y., Takeda, A., Yoshimura, T., Oshima, Y., Sonoda, K.-H., & Ishibashi, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068173 · Cited by 30
Age-related alterations in retinal neurovascular and inflammatory transcripts.
Kirk, C. A. V., VanGuilder, H. D., Young, M. M., Farley, J. A., Sonntag, W. E., & Freeman, W. M. (2011) · Europe PMC (PubMed Central) · Cited by 30
The Role of Angiotensin II/AT1 Receptor Signaling in Regulating Retinal Microglial Activation
Phipps, J. A., Vessey, K. A., Brandli, A. A., Nag, N., Tran, M. X., Jobling, A. I., & Fletcher, E. L. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22416 · Cited by 33
“For example, microglial-mediated inflammation has been implicated in a number of pathologies including Alzheimer’s disease and multiple sclerosis, while their response in the retina has been associated with the development of retinal degenerations such as age-related macular degeneration and diabetic retinopathy.(8,9)…”
BackgroundRittenhouse, K. D., Johnson, T. R., Vicini, P., Hirakawa, B. P., Kalabat, D. Y., Yang, A. H., Huang, W., & Basile, A. S. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13449 · Cited by 30
Zhao, Q., & Lai, K. (2023) · Experimental Eye Research · doi:10.1016/j.exer.2023.109770 · Cited by 31
Liu, X., Huang, K., Zhang, F., Huang, G., Wang, L., Wu, G., Ren, H., Yang, G., & Lin, Z. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02614-1 · Cited by 29
“AMD has long been regarded as a type of para-inflam-mation [279].”
BackgroundLiu, J., Tang, M., Harkin, K., Du, X., Luo, C., Chen, M., & Xu, H. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24618 · Cited by 29
“This immune defence system is operational when the retina suffers from endogenous insults such as oxidative damage during aging (Xu et al. 2009) or when IP is breached (Chen & Xu 2015).”
BackgroundSelf-citationYu, J., Yin, Y., Leng, Y., Zhang, J., Wang, C., Chen, Y., Li, X., Wang, X., Liu, H., Liao, Y., et al. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114842 · Cited by 31
Rohilla, M., Rishabh, R., Bansal, S., Garg, A., Dhiman, S., Dhankhar, S., Saini, M., Chauhan, S., Alsubaie, N., Batiha, G. E., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115881 · Cited by 29
Early degeneration of photoreceptor synapse inCcl2/Cx3cr1-deficient mice onCrb1rd8background
Zhang, J., Tuo, J., Cao, X., Shen, D., Li, W., & Chan, C. (2013) · Synapse · doi:10.1002/syn.21674 · Cited by 31
Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration
Kohno, H., Koso, H., Okano, K., Sundermeier, T. R., Saitô, S., Watanabe, S., Tsuneoka, H., & Sakai, T. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0408-3 · Cited by 29
“traditionally PCD is thought to occur due to genetic predisposition, environmental risk factors, and old age [1], accumulating clinical and experimental evidence suggests that retinal inflammation can accelerate PCD [2–5].”
BackgroundObasanmi, G., Lois, N., Armstrong, D., Hombrebueno, J. R., Lynch, A., Chen, M., & Xu, H. (2023) · Cells · doi:10.3390/cells12030467 · Cited by 31
“In diabetes, a hyperglycemic microenvironment inundated with dysregulated cytokine secretion and expression is a recipe for low-grade cellular activation and inflammation (parainflammation) that may persist to prompt the onset of diabetic complications, including DR and its progression [17,18].”
BackgroundSelf-citationEmerging therapeutic approaches in the management of retinal angiogenesis and edema
Truong, A., Wong, T. Y., & Khachigian, L. M. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0709-z · Cited by 27
“Retinal angiogenesis and edema are thought to result from conditions of chronic inflammation [10].”
BackgroundAdamus, G. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.01.005 · Cited by 28
“Furthermore, oxidized lipoproteins and free radicals contribute to tissue stress and low grade inflammation in retina [97].”
BackgroundThe Subtle Role of Para-inflammation in Modulating the Progression of Dry Eye Disease
Rolando, M., & Barabino, S. (2021) · Ocular Immunology and Inflammation · doi:10.1080/09273948.2021.1906908 · Cited by 29
Nutritional supplementation in the prevention and treatment of glaucoma
Chaudhry, S. G., Dunn, H., Carnt, N. A., & White, A. J. R. (2021) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2021.12.001 · Cited by 27
Bringmann, A., Hollborn, M., Kohen, L., & Wiedemann, P. (2016) · PubMed Central · Cited by 28
Jiang, M.-M., Zhou, Q., Liu, X.-Y., Shi, C., Chen, J., & Huang, X. (2017) · Medicine · doi:10.1097/md.0000000000006139 · Cited by 28
“Volume increases may be related to local tissue cell edema or microsomal activation.([17,18]) This may be a sign of nerve damage.”
BackgroundKarg, M. M., Moorefield, M., Hoffmann, E., Philipose, H., Krasniqi, D., Hoppe, C., Shu, D. Y., Shirahama, S., Ksander, B. R., & Saint-Geniez, M. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00358-4 · Cited by 27
“At the retinal/choroidal interface para-inflammation is manifested by complement activation in Bruch’s membrane and RPE cells, and microglia accumulation in the subretinal space [38].”
BackgroundControversial view of a genetically altered mouse model of focal retinal degeneration
Chu, X. K., Wang, Y., Ardeljan, D., Tuo, J., & Chan, C. (2012) · Bioengineered · doi:10.4161/bioe.22949 · Cited by 28
Aged macular degeneration: current therapeutics for management and promising new drug candidates
Jalil, A., Kanwar, R. K., & Kanwar, J. R. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.07.010 · Cited by 28
Metabolic syndrome and the aging retina
Roddy, G. W. (2021) · Current Opinion in Ophthalmology · doi:10.1097/icu.0000000000000747 · Cited by 27
Usategui‐Martín, R., Puertas‐Neyra, K., Galindo‐Cabello, N., Hernández‐Rodríguez, L., González‐Pérez, F., Rodríguez‐Cabello, J. C., González‐Sarmiento, R., Jimeno, J. C. P., & Fernandez‐Bueno, I. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.4.27 · Cited by 30
Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them
Kovács-Valasek, A., Rák, T., Pöstyéni, E., Csutak, A., & Gabriel, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108728 · Cited by 33
Krishnan, A., Sendra, V. G., Patel, D., Lad, A., Greene, M. K., Smyth, P., Gallaher, S. A., Herron, U. M., Scott, C. J., Genead, M. A., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1237016 · Cited by 27
“Flat mount immunohistochemistry (IHC) staining of isolectin-B4 showed that the control group had the largest lesion area (25,026.8 m m 2 ) that is reduced in the PolySia-NPs treated group at low and high doses to 19,573.6 m m 2 and 19,818.9 m m 2 respectively (Figures 7C, D).”
BackgroundInfluentialAn eye on the future of inflammasomes and drug development in AMD
Campbell, M., & Doyle, S. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1050-0 · Cited by 27
“With the initial intention of directing their clearance, instead, due to the near-indigestible nature of these aggregates, the inflammation persists causing further damage to the tissue in the surrounding area [61].”
Imaging of cellular aging in human retinal blood vessels
Catita, J., López‐Luppo, M., Ramos, D., Nacher, V., Navarro, M., Carretero, A., Sánchez‐Chardi, A., Mendes-Jorge, L., Rodríguez‐Baeza, A., & Ruberte, J. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.03.019 · Cited by 25
“Microglial cells are a specialized type of resident macrophages of the retina (Xu et al., 2009; Ardeljan and Chan, 2013).”
BackgroundVitrectomy in the management of diabetic macular edema in treatment-naïve patients
Michalewska, Z., Stewart, M. W., Landers, M. B., Bednarski, M., Adelman, R. A., & Nawrocki, J. (2017) · Canadian Journal of Ophthalmology · doi:10.1016/j.jcjo.2017.10.011 · Cited by 28
Hellgren, G., Willett, K. L., Engström, E., Thorsen, P., HOUGAARD, D. M., Jacobsson, B., Hellström, A., & Löfqvist, C. (2010) · Neonatology · doi:10.1159/000317779 · Cited by 27
Neuroretinal Degeneration in HIV Patients Without Opportunistic Ocular Infections in the cART Era
Demirkaya, N., Wit, F. W. N. M., Schlingemann, R. O., & Verbraak, F. D. (2015) · AIDS Patient Care and STDs · doi:10.1089/apc.2015.0091 · Cited by 26
Risk of retinal vein occlusion in patients with diabetes mellitus: A retrospective cohort study
Chang, Y., Ho, C., Chu, C., Wang, J., & Jan, R. (2020) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2020.108607 · Cited by 26
Age and intraocular pressure in murine experimental glaucoma
Pierdomenico, J. D., Henderson, D. C., Giammaria, S., Smith, V. L., Jamet, A. J., Smith, C. A., Hooper, M. L., & Chauhan, B. C. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.101021 · Cited by 25
Demirkaya, N., Wit, F. W. N. M., Berg, T., Kooij, K. W., Prins, M., Schlingemann, R. O., Abràmoff, M. D., Reiss, P., & Verbraak, F. D. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18537 · Cited by 26
“cART, or chronic inflammation.(18) HIV-NRD is part of a spectrum of abnormalities in HIV patients considered by some to potentially represent accelerated biological aging associated with HIV infection.”
BackgroundFundamental differences in patterns of retinal ageing between primates and mice
Kam, J. H., Weinrich, T. W., Shinhmar, H., Powner, M. B., Roberts, N. W., Aboelnour, A., & Jeffery, G. (2019) · Scientific Reports · doi:10.1038/s41598-019-49121-0 · Cited by 27
MicroRNA-223 Regulates Retinal Function and Inflammation in the Healthy and Degenerating Retina
Fernando, N., Wong, J. H. C., Das, S. J., Dietrich, C. A., Aggio‐Bruce, R., Cioanca, A. V., Wooff, Y., Chu‐Tan, J. A., Schümann, U., Ngo, C., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00516 · Cited by 26
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Mellal, K., Omri, S., Mulumba, M., Tahiri, H., Fortin, C. F., Dorion, M., Pham, H., García‐Ramos, Y., Zhang, J., Pundir, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-49472-8 · Cited by 28
Sorenson, C. M., Song, Y., Zaitoun, I. S., Wang, S., Hanna, B. A., Darjatmoko, S. R., Gürel, Z., Fisk, D. L., McDowell, C. M., McAdams, R. M., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.737426 · Cited by 25
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de Smet, M. D. (2017) · Developments in ophthalmology · doi:10.1159/000455279 · Cited by 26
The link between morphology and complement in ocular disease
Mohlin, C., Sandholm, K., Ekdahl, K. N., & Nilsson, B. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.05.028 · Cited by 25
Doktor, F., Prager, P., Wiedemann, P., Kohen, L., Bringmann, A., & Hollborn, M. (2018) · Purinergic Signalling · doi:10.1007/s11302-018-9631-6 · Cited by 25
Hussain, A. A., Lee, Y., & Marshall, J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100775 · Cited by 26
Innate immunity dysregulation in aging eye and therapeutic interventions
Das, S., Ahmad, Z., Suryawanshi, A. S., & Kumar, A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101768 · Cited by 24
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Pumphrey, S. A., Pizzirani, S., Pirie, C. G., & Needle, D. B. (2012) · Veterinary Ophthalmology · doi:10.1111/vop.12000 · Cited by 23
C-reactive protein and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus
Yang, X., Deng, Y. L., Gu, H., Lim, A., Snellingen, T., Liu, X.-P., Wang, N., Domalpally, A., Danis, R. P., & Liu, N. (2015) · International Journal of Ophthalmology · doi:10.18240/ijo.2016.01.19 · Cited by 23
Combination of ginsenoside Rb1 and Rd protects the retina against bright light-induced degeneration
Bian, M., Du, X., Wang, P., Cui, J., Xu, J., Gu, J., Zhang, T., & Chen, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-06471-x · Cited by 23
Herrmann, P., Cowing, J. A., Cristante, E., Liyanage, S. E., Ribeiro, J., Durán, Y., Abelleira, L. E., Carvalho, L. S., Bainbridge, J. W., Luhmann, U. F. O., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.05.019 · Cited by 20
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Jehs, T., Faber, C., Udsen, M. S., Jager, M. J., Clark, S. J., & Nissen, M. H. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18524 · Cited by 22
“In mice, an age-dependent accumulation of macrophages in the choroid occurs.(12,13) Moreover, it has been shown in mice as well as in humans that with age, the ratio of the antiinflammatory M2 macrophages to proinflammatory M1 macrophages increases in the eye,(14,15) suggesting age-dependent”
BackgroundBrain Damage - Bridging Between Basic Research and Clinics
González-Quevedo, A. (2012) · InTech eBooks · doi:10.5772/2174 · Cited by 21
Too, L. K., Hunt, N. H., & Simunovic, M. P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.635486 · Cited by 21
“In AMD, lipoproteins and free radicals are known initiators of retinal parainflammation, a form of chronic low-grade inflammation caused by endogenous stress (Xu et al., 2009).”
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Aqueous Humor Cytokines in Non-Proliferative Diabetic Retinopathy
Obadă, O., Pantalon, A. D., Rusu-Zota, G., Hăisan, A., Lupuşoru, S. I., Constantinescu, D., & Chiseliţă, D. (2022) · Medicina · doi:10.3390/medicina58070909 · Cited by 21
“Tissular stress induced by oxidative stress acts as a local trigger for para-inflammation, blood–retinal barrier breakdown, glial activation and increased cytokines production, all of which are characteristics of age-related retinal para-inflammation [41].”
BackgroundZhang, S., Xu, G., Wu, J., Liu, X., Fan, Y. Z., Chen, J., Wallace, G. G., & Gu, Q. (2023) · Small Methods · doi:10.1002/smtd.202300685 · Cited by 26
Complement Factor H Deficiency Results in Decreased Neuroretinal Expression of Cd59a in Aged Mice
Faber, C., Williams, J. A. E., Juel, H. B., Greenwood, J., Nissen, M. H., & Moss, S. E. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10385 · Cited by 22
Camelo, S., Lavelette, S., Guillonneau, X., Raoul, W., & Sennlaub, F. (2016) · Ophthalmologica · doi:10.1159/000446587 · Cited by 20
Palczewska, G., Maeda, A., Golczak, M., Arai, E., Dong, Z., Perusek, L., Kevany, B. M., & Palczewski, K. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.764563 · Cited by 21
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BackgroundAge-related pro-inflammatory and pro-angiogenic changes in human aqueous humor
Yan, Z., Rao, Y., Li, J.-K., Huang, Y., Zhao, P., & Li, J. (2018) · International Journal of Ophthalmology · doi:10.18240/ijo.2018.02.03 · Cited by 21
Sharif, U., Mahmud, N. M., Kay, P., Yang, Y. C., Harding, S. P., Grierson, I., Kamalden, T. A., Jackson, M. J., & Paraoan, L. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13944 · Cited by 21
“was described in the ageing retina as a stress response aimed at maintaining tissue integrity which is lost during chronic inflammation, contributing to the development of AMD.(53) Our data highlights the shifting in expression patterns of NF‐κB effectors as key mediators of inflammation in RPE cells in response to th…”
BackgroundInfluentialShaaban, Y. M., & Badran, T. A. F. (2019) · BMC Ophthalmology · doi:10.1186/s12886-019-1263-2 · Cited by 21
Macanian, J., & Sharma, S. C. (2022) · Encyclopedia · doi:10.3390/encyclopedia2040124 · Cited by 21
Jung, W. K., Park, S., Kim, H. R., Ryu, H. Y., Kim, Y. H., & Kim, J. (2021) · Current Issues in Molecular Biology · doi:10.3390/cimb43030142 · Cited by 20
“ROS production was accelerated under disease conditions and during the aging process [10], and frequently contributed to the tissue-damaging effects [9,31].”
BackgroundContribution of Interleukin-17A to Retinal Degenerative Diseases
Zhong, H., & Sun, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.847937 · Cited by 22
“accumulated in the damaged layer play a crucial role in the pathological changes (79, 80, 82).”
BackgroundFas Ligand-Fas Signaling Participates in Light-Induced Apoptotic Death in Photoreceptor Cells
Chang, Q., Peter, M. E., & Grassi, M. A. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8928 · Cited by 20
“The intracellular signals and mediators for apoptotic death in photoreceptors have been extensively studied.(11-13) However, the extrinsic mediators that activate the apoptotic death signal remain unknown as is the relevant mechanism by which dying photoreceptors affect the survival and function of”
BackgroundRisk mitigation of immunogenicity: a key to personalized retinal gene therapy
Varin, J., Morival, C., Maillard, N., Adjali, O., & Cronin, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312818 · Cited by 19
The trabecular meshwork in glaucoma: An inflammatory trabeculopathy?
Cela, D., Brignole‐Baudouin, F., Labbé, A., & Baudouin, C. (2021) · Journal Français d Ophtalmologie · doi:10.1016/j.jfo.2021.09.001 · Cited by 19
Update on Current and Future Management for Diabetic Maculopathy
Udaondo, P., Parravano, M., Vujosevic, S., Zur, D., & Chakravarthy, U. (2022) · Ophthalmology and Therapy · doi:10.1007/s40123-022-00460-8 · Cited by 19
Kumari, A., Ayala-Ramírez, R., Zenteno, J. C., Huffman, K., Šášik, R., Ayyagari, R., & Borooah, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-19351-w · Cited by 19
Homeostasis and dyshomeostasis of the retina
Zhang, C.-J., & Jin, Z. (2023) · Current Medicine · doi:10.1007/s44194-023-00021-6 · Cited by 25
The Impact of Aging on the Function of Retinal Ganglion Cells
Prinz, J., Walter, P., Liu, H., & Prokosch, V. (2024) · Klinische Monatsblätter für Augenheilkunde · doi:10.1055/a-2239-0290 · Cited by 19
“Microglial cells are the main resident immune cells in the retina with macrophage-like properties [69].”
BackgroundDeveloping Cell-Based Therapies for RPE-Associated Degenerative Eye Diseases
M’Barek, K. B., Habeler, W., Régent, F., & Monville, C. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-28471-8_3 · Cited by 19
Otsuki, Y., Ito, E., Mukai, A., Ueno, M., Yamawaki, T., Sotozono, C., Kinoshita, S., & Hamuro, J. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108496 · Cited by 19
Molecular Features of Classic Retinal Drugs, Retinal Therapeutic Targets and Emerging Treatments
Arrigo, A., & Bandello, F. M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13071102 · Cited by 18
“Furthermore, the progressive degeneration of retinal cells may stimulate complement activation and lead to the accumulation of microglia and inflammatory cells, and the onset and progression of proinflammatory phenomena [62].”
BackgroundChen, R., Chen, Y., Zhang, J., Wang, W., Hu, W., He, M., & Zhu, Z. (2023) · Acta Diabetologica · doi:10.1007/s00592-023-02199-5 · Cited by 17
“Of note, ageing might lead to retinal neuron apoptosis and loss through various pathways including DNA damage, telomere dysfunction, oxidative stress and chronic inflammation [27, 34, 44].”
Wang, Y., Abu-Asab, M. S., Yu, C., Tang, Z., Shen, D., Tuo, J., Li, X., & Chan, C. (2014) · Laboratory Investigation · doi:10.1038/labinvest.2014.60 · Cited by 19
Bonyadi, M. J., Foruzandeh, Z., Gol, T. M., Fotouhi, N., Soheilian, M., Bonyadi, M. H. J., Javadzadeh, A., Moein, H.-R., & Yaseri, M. (2016) · Acta Ophthalmologica · doi:10.1111/aos.13143 · Cited by 18
“It has been shown that the inflammatory responses including microglial activation and subretinal migration have important role in the ageing retina (Xu et al. 2009).”
BackgroundRolle des alternden visuellen Systems bei Glaukomen
Unterlauft, J. D., & Böhm, M. (2017) · Der Ophthalmologe · doi:10.1007/s00347-016-0430-6 · Cited by 19
“Es handelt sich dabei um eine chronische Low-grade-Entzündung ohne Infektbeteiligung, die scheinbar einen Anteil an den Alterungsvorgängen hat [29].”
MethodInfluentialSchnabolk, G., Stauffer, K. M., O’Quinn, E. C., Coughlin, B. A., Kunchithapautham, K., & Rohrer, B. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.10.005 · Cited by 19
“However, if the stressor is not removed, para-inflammation gives way chronic inflammation, and pathology may develop (Whitcup et al., 2013; Xu et al., 2009).”
BackgroundMadendağ, Y., Açmaz, G., Ataş, M., Şahin, E., Tayyar, A. T., Madendağ, İ. Ç., Özdemir, F., & Şenol, V. (2017) · Medical Science Monitor · doi:10.12659/msm.905183 · Cited by 18
“In our study we also found that the average RNFL thickness, particularly the NI and TI parts, was significantly decreased in women using OCP.”
BackgroundInfluentialBian, Z.-M., Field, M. G., Elner, S., Kahlenberg, J., & Elner, V. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.02.014 · Cited by 18
“…but relatively low, IL-1β and MCP-1 secretion observed in primary hRPE cells is consistent with the chronic, low-grade inflammation that is characteristic of AMD, atherosclerosis and other age-related and inflammatory conditions (Buschini et al., 2011; Chaurasia et al., 2009; Xu et al., 2009).”
BackgroundResultYang, X., Deng, Y. L., Gu, H., Ren, X., Lim, A., Snellingen, T., Liu, X., Wang, N., Pak, J. W., Liu, N., et al. (2016) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2014-306078 · Cited by 17
Zicarelli, F., Azzolini, C., Cornish, E. E., Agarwal, A. K., Khochtali, S., Airaldi, M., Khairallah, M., Viola, F., Staurenghi, G., McCluskey, P., et al. (2020) · Retina · doi:10.1097/iae.0000000000002984 · Cited by 17
“001 Males 16 (23) 21 (30) 24 (53) Females 54 (77) 49 (70) 21 (46) BCVA logMAR (SD) at presentation 0.”
An, Y., Park, S. P., & Kim, Y. (2021) · International Ophthalmology · doi:10.1007/s10792-021-01798-x · Cited by 17
Reichenbach, A., & Bringmann, A. (2015) · Colloquium Series on Neuroglia in Biology and Medicine From Physiology to Disease · doi:10.4199/c00122ed1v01y201412ngl003 · Cited by 18
Re-programming immunosurveillance in persistent non-infectious ocular inflammation
Epps, S. J., Boldison, J., Stimpson, M. L., Khera, T. K., Lait, P. J. P., Copland, D. A., Dick, A. D., & Nicholson, L. B. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.03.001 · Cited by 17
“The common use of adjuvants in these models may lead to concurrent para-inflammatory reactions to infections components (Forrester et al., 2013; Xu et al., 2009).”
BackgroundÇetin, E. N., Kutlu, S. S., Parça, O., Kutlu, M., & Pekel, G. (2018) · Retina · doi:10.1097/iae.0000000000002146 · Cited by 17
Prokopiou, E., Kolovos, P., Kalogerou, M., Neokleous, A., Papagregoriou, G., Deltas, C., Malas, S., & Georgiou, T. (2017) · BMJ Open Ophthalmology · doi:10.1136/bmjophth-2016-000056 · Cited by 16
Adamus, G. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.672444 · Cited by 16
“Microglia that includes microglia (resident macrophages), perivascular macrophages, and dendritic cells play an important role in the retinal immune defense (111, 112).”
BackgroundDu, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00432-9 · Cited by 16
Self-citationGrand Challenges in Ocular Inflammatory Diseases
Xu, H., & Rao, N. A. (2022) · Frontiers in Ophthalmology · doi:10.3389/fopht.2022.756689 · Cited by 18
“Indeed, the aging retina is accompanied by a sustained low-level of inflammation (parainflammation) characterized by microglial activation, subretinal accumulation and low levels of complement activation (32).”
BackgroundSelf-citationKu, L.-C., Sheu, M., Cheng, H., Lee, C., Tsai, Y.-C., Tsai, C.-Y., Lin, K., Lai, L.-C., & Lai, D. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114476 · Cited by 16
Mechanism and therapeutic targets of circulating immune cells in diabetic retinopathy
Zhao, B., Zhao, Y., & Sun, X. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107505 · Cited by 19
Guymer, R. H., Cipriani, T., Rittenhouse, K. D., Lim, L. L., Robman, L. D., Li, W., Wang, W., Deng, S., & Banerjee, P. (2015) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-015-2970-x · Cited by 16
“When such an inflammatory process occurs in the retina, it results in the release of circulating inflammatory mediators [16] and the detection of these in the serum has been considered a”
Background
Metadata
- Authors
- Xu, H., Chen, M., & Forrester, J. V.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Xu, Heping
- 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)
- 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
- 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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