Immune Activation in Retinal Aging: A Gene Expression Study
Abstract
PURPOSE: To investigate changes in gene expression during aging of the retina in the mouse. METHODS: Total RNA was extracted from the neuroretina of young (3-month-old) and old (20-month-old) mice and processed for microarray analysis. Age-related, differentially expressed genes were assessed by the empiric Bayes shrinkage-moderated t-statistics METHOD: Statistical significance was based on dual criteria of a ratio of change in gene expression >2 and a P < 0.01. Differential expression in 11 selected genes was further verified by real-time PCR. Functional pathways involved in retinal aging were analyzed by an online software package (DAVID-2008) in differentially expressed gene lists. Age-related changes in differential expression in the identified retinal molecular pathways were further confirmed by immunohistochemical staining of retinal flat mounts and retinal cryosections. RESULTS: With aging of the retina, 298 genes were upregulated and 137 genes were downregulated. Functional annotation showed that genes linked to immune responses (Ir genes) and to tissue stress/injury responses (TS/I genes) were most likely to be modified by aging. The Ir genes affected included those regulating leukocyte activation, chemotaxis, endocytosis, complement activation, phagocytosis, and myeloid cell differentiation, most of which were upregulated, with only a few downregulated. Increased microglial and complement activation in the aging retina was further confirmed by confocal microscopy of retinal tissues. The most strongly upregulated gene was the calcitonin receptor (Calcr; >40-fold in old versus young mice). CONCLUSIONS: The results suggest that retinal aging is accompanied by activation of gene sets, which are involved in local inflammatory responses. A modified form of low-grade chronic inflammation (para-inflammation) characterizes these aging changes and involves mainly the innate immune system. The marked upregulation of Calcr in aging mice most likely reflects this chronic inflammatory/stress response, since calcitonin is a known systemic biomarker of inflammation/sepsis.
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Retinal inflammation and degeneration have been reported to commence earlier than 24 months in rodents.
“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 [22]
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829 · see citing works
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327 · see citing works
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 · see citing works
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618 · see citing works
GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways
Dahlquist, K. D., Salomonis, N., VRANIZAN, K. M., Lawlor, S. C., & Conklin, B. R. (2002) · Nature Genetics · doi:10.1038/ng0502-19 · Cited by 958 · see citing works
Anderson, D. H., Radeke, M. J., Gallo, N. B., Chapin, E. A., Johnson, P. T., Curletti, C. R., Hancox, L. S., Hu, J., Ebright, J. N., Malek, G., et al. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.11.003 · Cited by 727 · see citing works
Para-Inflammation in the Aging Retina
Xu, H., Chen, M., & Forrester, J. V. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.06.001 · Cited by 659 · see citing works
Self-citationMolecular pathology of age-related macular degeneration
Ding, X., Patel, M., & Chan, C.-C. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2008.10.001 · Cited by 582 · cited 1× · see citing works
“It is well known that certain genetic and environmental factors may predispose individuals to glaucoma,(1) diabetic retinopathy,(2) or age-related macular degeneration.(3,4) We hypothesize that agerelated changes in the retina may provide a background that increases susceptibility to the development of these diseases.”
BackgroundBecker, K. L., Nylen, E. S., White, J. C., Müller-Stich, B. P., & Snider, R. H. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021444 · Cited by 580 · see citing works
Risk Factors for Glaucoma Onset and Progression
Coleman, A. L., & Miglior, S. (2008) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2008.08.006 · Cited by 549 · see citing works
Ubiquitous Expression of the Calcitonin-I Gene in Multiple Tissues in Response to Sepsis1
Müller-Stich, B. P., White, J. C., Nylen, E. S., Snider, R. H., Becker, K. L., & Habener, J. F. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.1.7089 · Cited by 446 · see citing works
Immunological mechanisms in the pathogenesis of diabetic retinopathy
Adamis, A. P., & Berman, A. J. (2008) · Seminars in Immunopathology · doi:10.1007/s00281-008-0111-x · Cited by 323 · see citing works
Role of complement in neurodegeneration and neuroinflammation
Bonifati, D. M., & Kishore, U. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.03.007 · Cited by 310 · see citing works
Xu, H., Chen, M., Manivannan, A., Lois, N., & Forrester, J. V. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2007.00351.x · Cited by 277 · see citing works
Self-citationGenMAPP 2: new features and resources for pathway analysis
Salomonis, N., Hanspers, K., Zambon, A. C., VRANIZAN, K. M., Lawlor, S. C., Dahlquist, K. D., Doniger, S. W., Stuart, J. M., Conklin, B. R., & Pico, A. R. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-217 · Cited by 255 · see citing works
Glial changes following an excitotoxic lesion in the CNS—I. Microglia/macrophages
Marty, S., Dusart, I., & Peschanski, M. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90268-s · Cited by 212 · see citing works
Diabetic microvascular complications: can patients at risk be identified? A review
Girach, A., Manner, D. H., & Porta, M. (2006) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2006.01175.x · Cited by 177 · see citing works
Chen, M., Forrester, J. V., & Xu, H. (2007) · Experimental Eye Research · doi:10.1016/j.exer.2006.11.015 · Cited by 175 · see citing works
Self-citationMethods of Microarray Data Analysis V
McConnell, P., Lin, S. M., & Hurban, P. (2007) · Springer eBooks · doi:10.1007/978-0-387-34569-7 · Cited by 168 · see citing works
Serum Calcitonin Precursors in Sepsis and Systemic Inflammation1
Whang, K. T., Steinwald, P. M., White, J. C., Nylen, E. S., Snider, R. H., Simon, G. L., Goldberg, R. L., & Becker, K. L. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.9.5129 · Cited by 167 · see citing works
Immunopathological aspects of age-related macular degeneration
Patel, M. M., & Chan, C. (2008) · Seminars in Immunopathology · doi:10.1007/s00281-008-0112-9 · Cited by 163 · see citing works
Complement, Age-Related Macular Degeneration and a Vision of the Future
Gehrs, K. M. (2010) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2010.18 · Cited by 157 · see citing works
Turnover of resident retinal microglia in the normal adult mouse
Xu, H., Chen, M., Mayer, E. J., Forrester, J. V., & Dick, A. D. (2007) · Glia · doi:10.1002/glia.20535 · Cited by 153 · see citing works
Self-citationLYVE-1–Positive Macrophages Are Present in Normal Murine Eyes
Xu, H., Chen, M., Reid, D. M., & Forrester, J. V. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0783 · Cited by 132 · see citing works
Self-citationChen, H., Liu, B., Lukas, T. J., & Neufeld, A. H. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002339 · Cited by 129 · see citing works
Immunoregulation of retinal ganglion cell fate in glaucoma
Wax, M. B., & Tezel, G. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2009.02.005 · Cited by 124 · see citing works
Review of Genetics in Age Related Macular Degeneration
Montezuma, S. R., Sobrin, L., & Seddon, J. M. (2007) · Seminars in Ophthalmology · doi:10.1080/08820530701745140 · Cited by 108 · see citing works
Identification of Novel Dendritic Cell Populations in Normal Mouse Retina
Xu, H., Dawson, R., Forrester, J. V., & Liversidge, J. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0697 · Cited by 102 · see citing works
Self-citationChen, M., Muckersie, E., Robertson, M., Forrester, J. V., & Xu, H. (2008) · Experimental Eye Research · doi:10.1016/j.exer.2008.09.005 · Cited by 99 · see citing works
Self-citationYin and Yang: complement activation and regulation in Alzheimer’s disease
Shen, Y., & Meri, S. (2003) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2003.08.001 · Cited by 89 · see citing works
Calcitonin receptor antibodies in the identification of osteoclasts
Quinn, J. M. W., Morfis, M., Lam, M. H. C., Elliott, J., Kartsogiannis, V, Williams, E. D., Gillespie, M. T., Martin, T. J., & Sexton, P. M. (1999) · Bone · doi:10.1016/s8756-3282(99)00094-0 · Cited by 85 · see citing works
Chan‐Ling, T., Hughes, S., BAXTER, L., Rosinova, E., McGregor, I. S., Morcos, Y., van Nieuwenhuyzen, P. S., & Hu, P. (2007) · Microcirculation · doi:10.1080/10739680601073451 · Cited by 79 · see citing works
HOFFMANN, G. E., Czechowski, M., Schloesser, M., & Schobersberger, W. (2002) · Critical Care Medicine · doi:10.1097/00003246-200209000-00023 · Cited by 73 · see citing works
Slagboom, P. E., de Leeuw, W. J. F., & Vijg, J. (1990) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(90)90042-e · Cited by 68 · see citing works
Autoantigens act as tissue-specific chemoattractants
Oppenheim, J. J., Dong, H., Plötz, P. H., Caspi, R. R., Dykstra, M. L., Pierce, S. K., Martinꝉ, R., Carlos, C. A., Finn, O. J., Koul, O., et al. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.1004623 · Cited by 49 · see citing works
Transgenic Mice Reveal Novel Sites of Calcitonin Receptor Gene Expression during Development
Jagger, C., Chambers, T. J., & Pondel, M. D. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3093 · Cited by 39 · see citing works
Hoshiya, H., Meguro, M., Kashiwagi, A., Okita, C., & Oshimura, M. (2003) · Journal of Human Genetics · doi:10.1007/s10038-003-0006-6 · Cited by 35 · see citing works
Effect of calcitonin on different inflammatory models
Abdullahi, S., Martelli, E. A., Bramm, E., Franco, L., & Velo, G. P. (1977) · Inflammation Research · doi:10.1007/bf02111126 · Cited by 18 · see citing works
Díaz‐Uriarte, R., Al‐Shahrour, F., & Dopazo, J. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-48354-8_16 · Cited by 11 · see citing works
Mori, I., Ishii, A., Nakamura, A., Nakamura, M., Nakagomi, N., Takeda, K., & Kakudo, K. (2006) · PubMed · Cited by 5 · see citing works
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Baudouin, C., Kolko, M., Parsadaniantz, S. M., & Messmer, E. S. B. M. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100916 · Cited by 470 · see citing works
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Chen, M., & Xu, H. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri0615-239r · Cited by 381 · see citing works
Self-citationParker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G. M., Pontifex, M. G., Telatin, A., Baker, D., Jones, E., et al. (2022) · Microbiome · doi:10.1186/s40168-022-01243-w · Cited by 368 · see citing works
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Chen, M., Luo, C., Zhao, J., Devarajan, G., & Xu, H. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.10.003 · Cited by 305 · see citing works
Self-citationAging is not a disease: Distinguishing age-related macular degeneration from aging
Ardeljan, D., & Chan, C. (2013) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2013.07.003 · Cited by 243 · see citing works
Kinnunen, K., Petrovski, G., Moe, M. C., Berta, A., & Kaarniranta, K. (2011) · Acta Ophthalmologica · doi:10.1111/j.1755-3768.2011.02179.x · Cited by 197 · see citing works
Targeting the complement system for the management of retinal inflammatory and degenerative diseases
Xu, H., & Chen, M. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.03.001 · Cited by 162 · see citing works
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Akhtar‐Schäfer, I., Wang, L., Krohne, T. U., Xu, H., & Langmann, T. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708259 · Cited by 127 · see citing works
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Guo, L., Choi, S., Bikkannavar, P., & Cordeiro, M. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.804782 · Cited by 129 · see citing works
Rutar, M., Natoli, R., & Provis, J. M. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-221 · Cited by 121 · see citing works
Ma, W., Cojocaru, R. I., Gotoh, N., Gieser, L. M., Villasmil, R., Cogliati, T., Swaroop, A., & Wong, W. T. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.022 · Cited by 107 · see citing works
Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid.
Luo, C., Chen, M., & Xu, H. (2011) · PubMed Central · Cited by 107 · see citing works
Self-citationLee, V., Rekhi, E., Kam, J. H., & Jeffery, G. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.12.002 · Cited by 104 · see citing works
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Chan, H.-N., Zhang, X. J., Ling, X.-T., Bui, C. H. T., Wang, Y., Ip, P., Chu, W. K., Chen, L. J., Tham, C. C. Y., Yam, J. C. S., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084226 · Cited by 103 · see citing works
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Pauly, D., Agarwal, D., Dana, N., Schäfer, N., Biber, J., Wunderlich, K. A., Jabri, Y., Straub, T., Zhang, N. R., Gautam, A. K., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.084 · Cited by 100 · see citing works
Kokkinopoulos, I., Colman, A., Hogg, C. R., Heckenlively, J. R., & Jeffery, G. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.04.014 · Cited by 94 · see citing works
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Ma, L., Kaufman, Y., Zhang, J., & Washington, I. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.178657 · Cited by 83 · see citing works
Kam, J. H., Lenassi, E., Malik, T. H., Pickering, M. C., & Jeffery, G. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.04.008 · Cited by 82 · see citing works
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Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions
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Camelo, S. (2014) · Autoimmune Diseases · doi:10.1155/2014/532487 · Cited by 67 · see citing works
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Chen, M., Zhao, J., Luo, C., Pandi, S. P. S., Peñalva, R. G., Fitzgerald, D. C., & Xu, H. (2012) · Glia · doi:10.1002/glia.22315 · Cited by 67 · see citing works
Self-citationVitamin D and Age-Related Macular Degeneration
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Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation
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Retinal and brain microglia in multiple sclerosis and neurodegeneration
Choi, S., Guo, L., & Cordeiro, M. F. (2021) · Cells · doi:10.3390/cells10061507 · Cited by 63 · see citing works
Chaudhary, S., Namavari, A., Yco, L., Chang, J.-H., Sonawane, S. S., Khanolkar, V., Sarkar, J., & Jain, S. K. (2012) · Cornea · doi:10.1097/ico.0b013e318247b60e · Cited by 58 · see citing works
Mendiola, A. S., Garza, R., Cardona, S. M., Mythen, S. A., Lira, S. A., Akassoglou, K., & Cardona, A. E. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00303 · Cited by 57 · see citing works
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Zhao, T., Gao, J., Van, J., To, E. C., Wang, A., Cao, S., Cui, J. Z., Guo, J., Lee, M., McGeer, P. L., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0337-1 · Cited by 44 · see citing works
Singh, A., Subhi, Y., Nielsen, M. K., Falk, M. K., Matzen, S. M. H., Sellebjerg, F. T., & Sørensen, T. L. (2017) · Scientific Reports · doi:10.1038/s41598-017-00741-4 · Cited by 44 · see citing works
Yi, C., Liu, J., Deng, W., Luo, C., Qi, J., Chen, M., & Xu, H. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02731-y · Cited by 43 · see citing works
Self-citationDrusen maculopathy: a risk factor for visual deterioration
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Chen, M., Hombrebueno, J. R., Luo, C., Peñalva, R. G., Zhao, J., Colhoun, L. M., Pandi, S. P. S., Forrester, J. V., & Xu, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061381 · Cited by 43 · see citing works
Self-citationAge-Related Macular Degeneration: A Disease of Systemic or Local Complement Dysregulation?
Warwick, A., Khandhadia, S., Ennis, S., & Lotery, A. J. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3041234 · Cited by 41 · see citing works
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González-Peña, D., Nixon, S. E., O’Connor, J. C., Southey, B. R., Lawson, M. A., McCusker, R. H., Borras, T., Machuca, D., Hernández, Á. G., Dantzer, R., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150858 · Cited by 41 · see citing works
Karlstetter, M., & Langmann, T. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3209-8_27 · Cited by 41 · see citing works
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Age-related alterations in retinal neurovascular and inflammatory transcripts.
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Zhang, Y., & Wong, W. T. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-66014-7_5 · Cited by 27 · see citing works
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Kovács-Valasek, A., Rák, T., Pöstyéni, E., Csutak, A., & Gabriel, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108728 · Cited by 30 · see citing works
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 · see citing works
Lee, D., Nakai, A., Miwa, Y., Tomita, Y., Serizawa, N., Katada, Y., Hatanaka, Y., Tsubota, K., Negishi, K., & Kurihara, T. (2021) · BioMed Research International · doi:10.1155/2021/7727648 · Cited by 26 · see citing works
Lee, D., Nakai, A., Miwa, Y., Tomita, Y., Kunimi, H., Chen, J., Ikeda, S., Tsubota, K., Negishi, K., & Kurihara, T. (2022) · The FASEB Journal · doi:10.1096/fj.202200455rrr · Cited by 27 · see citing works
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 · see citing works
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 · see citing works
Assessment of Retinal Function and Morphology in Aging Ccl2 Knockout Mice
Vessey, K. A., Waugh, M., Jobling, A. I., Phipps, J. A., Ho, T., Trogrlic, L., Greferath, U., & Fletcher, E. L. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15334 · Cited by 25 · see citing works
Sun, R., Feng, J., & Wang, J. (2023) · Aging and Disease · doi:10.14336/ad.2023.0621 · Cited by 26 · see citing works
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 · see citing works
Vascular Inflammation Risk Factors in Retinal Disease
Soto, I., Krebs, M. P., Reagan, A. M., & Howell, G. R. (2019) · Annual Review of Vision Science · doi:10.1146/annurev-vision-091517-034416 · Cited by 22 · see citing works
Retinal phagocytes in age-related macular degeneration
Kim, S. (2015) · Macrophage · doi:10.14800/macrophage.698 · Cited by 21 · see citing works
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 21 · see citing works
Differentially expressed microRNAs in kidney biopsies from various subtypes of nephrotic children
Lü, M., Wang, C., Yuan, Y., Zhu, Y., Yin, Z., Xia, Z., & Zhang, C. (2015) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2015.10.003 · Cited by 21 · see citing works
Retinal Changes Precede Visual Dysfunction in the Complement Factor H Knockout Mouse
Williams, J. A. E., Greenwood, J., & Moss, S. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068616 · Cited by 20 · see citing works
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 · see citing works
High-Fat Diet Alters the Retinal Transcriptome in the Absence of Gut Microbiota
Dao, D., Xie, B., Nadeem, U., Xiao, J. F., Movahedan, A., D’Souza, M., Leone, V., Hariprasad, S. M., Chang, E. B., Sulakhe, D., et al. (2021) · Cells · doi:10.3390/cells10082119 · Cited by 19 · see citing works
Abokyi, S., & Tse, D. Y. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-02033 · Cited by 17 · see citing works
Çetin, E. N., Kutlu, S. S., Parça, O., Kutlu, M., & Pekel, G. (2018) · Retina · doi:10.1097/iae.0000000000002146 · Cited by 17 · see citing works
Du, 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 · see citing works
Self-citationGenetic context modulates aging and degeneration in the murine retina
Marola, O. J., MacLean, M., Cossette, T. L., Diemler, C. A., Hewes, A. A., Reagan, A. M., Kanyinda, J. N., Skelly, D. A., & Howell, G. R. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00800-9 · Cited by 15 · see citing works
Palacios, A. G., Zhang, S. X., & Acosta, M. L. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70497 · Cited by 15 · see citing works
Ageing of the Retina and Retinal Pigment Epithelium
Boulton, M. (2012) · Springer eBooks · doi:10.1007/978-3-642-22107-1_3 · Cited by 15 · see citing works
Wang, J.-H., Wong, R. C. B., & Liu, G. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.4.32 · Cited by 14 · see citing works
The Complement System as a Therapeutic Target in Retinal Disease
Ong, J., Zarnegar, A., Selvam, A., Driban, M., & Chhablani, J. K. (2024) · Medicina · doi:10.3390/medicina60060945 · Cited by 14 · see citing works
Auler, N., Tonner, H., Pfeiffer, N., & Grus, F. H. (2021) · Biology · doi:10.3390/biology10121296 · Cited by 15 · see citing works
MANF delivery improves retinal homeostasis and cell replacement therapies in ageing mice
Neves, J., Chirco, K. R., Cedron-Craft, W., Chew, S., Zhu, J., Jasper, H., & Lamba, D. A. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110893 · Cited by 13 · see citing works
Luo, C., Zhao, J., Chen, M., & Xu, H. (2018) · Aging · doi:10.18632/aging.101474 · Cited by 13 · see citing works
Self-citationDrusen and Pro-inflammatory Mediators in the Post-Mortem Human Eye
Jiang, K., To, E. C., Cui, J. Z., & Cao, S. (2012) · Journal of Clinical & Experimental Ophthalmology · doi:10.4172/2155-9570.1000208 · Cited by 13 · see citing works
Prenatal smoke exposure: Effects on infant auditory system and placental gene expression
Katbamna, B., Klutz, N., Pudrith, C., Lavery, J. P., & Ide, C. F. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2013.04.008 · Cited by 12 · see citing works
mTORC1 Activation in Chx10‐Specific Tsc1 Knockout Mice Accelerates Retina Aging and Degeneration
Rao, Y., Zhou, Y., Zhou, W., Li, J.-K., Li, B., & Li, J. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6715758 · Cited by 12 · see citing works
670 nm LED ameliorates inflammation in the CFH−/− mouse neural retina
Kokkinopoulos, I. (2013) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2013.03.003 · Cited by 12 · see citing works
Luo, Y., Xia, Y., Gong, X., Hao, M., Wei, Q., & Liao, L. (2026) · BMC Ophthalmology · doi:10.1186/s12886-025-04559-x · Cited by 14 · see citing works
Protecting the aging eye with hydrogen sulfide
George, A. K., Homme, R. P., Stanišić, D., Tyagi, S. C., & Singh, M. (2020) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2020-0216 · Cited by 10 · see citing works
The Potential of Lisosan G as a Possible Treatment for Glaucoma
Amato, R., Rossino, M. G., Cammalleri, M., Timperio, A. M., Fanelli, G., Monte, M. D., Pucci, L., & Casini, G. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.719951 · Cited by 10 · see citing works
Molecular Age-Related Changes in the Anterior Segment of the Eye
Hernández-Zimbrón, L. F., Gulías-Cañizo, R., Golzarri, M. F., Martínez-Báez, B. E., Quiroz–Mercado, H., & González-Salinas, R. (2017) · Journal of Ophthalmology · doi:10.1155/2017/1295132 · Cited by 10 · see citing works
Microglia heterogeneity during neuroinflammation and neurodegeneration in the mouse retina
Rao, B., Liu, X., Xiao, J., Wu, X., He, F., Yang, Q., Zhao, W., Lin, X., & Zhang, J. (2024) · Brain Structure and Function · doi:10.1007/s00429-024-02875-4 · Cited by 8 · see citing works
Heterochronic Fecal Microbiota Transfer Reverses Hallmarks of the Aging Murine Gut, Eye and BrainPreprint
Parker, A., Romano, S., Ansorge, R., Aboelnoer, A., Gall, G. L., Savva, G. M., Telatin, A., Jones, E. J., Baker, D., Rudder, S. J., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3811833 · Cited by 8 · see citing works
Realini, G., Amato, R., Rasa, S. M. M., Ceccatelli, R., Cannavale, A., Bottoni, L., Marchini, F., Minetti, A., Giustarini, D., Canovai, A., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103914 · Cited by 7 · see citing works
The role of inflammation in Age-related Macular Degeneration
Ermakova, N. A. (2018) · Russian Annals of Ophthalmology · doi:10.17116/oftalma2018134061116 · Cited by 7 · see citing works
Systemic changes in neovascular age-related macular degeneration.
Singh, A. (2014) · PubMed · Cited by 7 · see citing works
The effects of time restricted feeding on age-related changes in the mouse retina
Huston, C. A., Milan, M., Vance, M. L., Bickel, M. A., Miller, L. R., Negri, S., Hibbs, C. L., Vaden, H., Hayes, L. N., Csiszar, A., et al. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112510 · Cited by 6 · see citing works
GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis
Xu, X., Ding, X., Wang, Z., Ye, S., Xu, J., Liang, Z., Luo, R., Xu, J., Li, X., & Ren, Z. (2024) · Microvascular Research · doi:10.1016/j.mvr.2024.104689 · Cited by 5 · see citing works
Bayesian Quantitative Electrophysiology and Its Multiple Applications in Bioengineering
Barr, R. C., Nolte, L. W., & Pollard, A. E. (2010) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2010.2089375 · Cited by 5 · see citing works
Relationship Between Periodontitis and Open Angle Glaucoma
Noh, J. H., Lee, M. Y., Yoo, C., Sung, K. R., & Kim, J. M. (2025) · Journal of Glaucoma · doi:10.1097/ijg.0000000000002584 · Cited by 4 · see citing works
Tissue-Specific Gamma-Flicker Light Noninvasively Ameliorates Retinal Aging
Sheng, W., Lv, D., Cui, Z., Wang, Y., Lin, B., Tang, S., & Chen, J. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01160-w · Cited by 3 · see citing works
- Authors
- Chen, M., Muckersie, E., Forrester, J. V., & Xu, H.
- Affiliations
- Queen's University Belfast (GB)
- University of Aberdeen (GB)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2010-11-01
- Volume
- 51
- Issue
- 11
- Pages
- 5888
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2096107242
- Cited by
- 130
- References
- 41
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 7 · 2022: 15 · 2021: 22 · 2020: 3 · 2019: 2 · 2018: 7 · 2017: 8 · 2016: 4 · 2015: 9 · 2014: 5 · 2013: 9 · 2012: 10
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- retinal aging, neuroretina, gene expression, immune activation, chronic inflammation, innate immunity, microglia, complement activation, calcitonin receptor, calcitonin, leukocyte activation
- MeSH terms
- Aging, Animals, Eye Proteins, Genes, MHC Class II, Male, Mice, Inbred C57BL, Retina, RNA, Gene Expression, Microscopy, Confocal, Fluorescent Antibody Technique, Indirect, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice
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