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C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration
Open accessAbstract
BACKGROUND: There is increasing evidence that inflammation and immune-mediated processes (complement activation) play an important role in age-related macular degeneration (AMD) pathogenesis. A genetic variation in the gene encoding complement factor H (CFH) and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have consistently been shown to be associated with an increased risk for AMD. In the present study, we examined the immunolocalisation of CRP and CFH in aged control human donor eyes (n=10; mean age 79 years) and eyes with AMD (n=18; mean age 83 years). METHODS: Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against CRP and CFH on cryopreserved tissue sections from disc/macular blocks. Three independent masked observers scored the reaction product (0-8). RESULTS: In aged control eyes, the retinal pigment epithelium/Bruch's membrane/choriocapillaris (RPE/BrM/CC) complex including intercapillary septa (ICS) had the most prominent immunostaining for CRP and CFH. CRP was significantly higher than controls in BrM/CC/ICS and choroidal stroma in early and wet AMD eyes (p<0.05). In contrast, CFH was significantly lower in BrM/CC/ICS complex of AMD choroids than in controls (p<0.05). Interestingly, CRP and CFH were significantly reduced in BrM/CC/ICS complex in atrophic area of macula in geographical atrophy (p<0.05). Drusen and basal laminar deposits were intensely positive for CRP and CFH. CONCLUSION: These immunohistochemical findings show that changes in distribution and relative levels of CRP and CFH were evident in early and late AMD eyes. This suggests that high levels of CRP and insufficient CFH at the retina/choroid interface may lead to uncontrolled complement activation with associated cell and tissue damage. This study supports the hypothesis that inflammation and immune-mediated mechanisms are involved in the pathogenesis of AMD.
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“Reduced expression of FH and CD46 by RPE cells is observed in AMD, and this coincides with increased deposition of the MAC and cell lysis [132,133].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [132]
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Cites
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C-reactive protein: a critical update
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“C-reactive protein (CRP) is an acute-phase reactant that is synthesised predominantly in the liver and adipocytes,”
BackgroundComplement 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
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Complement factor H polymorphism and age-related macular degeneration
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Complement factor H variant increases the risk of age-related macular degeneration
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Drusen proteome analysis: an approach to the etiology of age-related macular degeneration
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“and other molecules that mediate local inflammation.”
Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies
Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., & Adamis, A. P. (2003) · Survey of Ophthalmology · doi:10.1016/s0039-6257(03)00030-4 · Cited by 959 · cited 1×
“INTRODUCTION Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly population worldwide.(1) Recent studies provide increasing evidence that inflammation and immune-mediated processes play an important role in AMD pathogenesis.”
Background
Cited by
Sorted by citations
Bhutto, I. A., & Lutty, G. A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.005 · Cited by 1,028
“In contrast, immunostaining for CFH was significantly reduced in the BrMb/CC complex including the ICS in eyes with early and wet AMD (Bhutto et al., 2011).”
BackgroundInfluentialSelf-citationThe impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K. B., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 843
“…altered pattern is protective or pathologic is unclear at this time, but studies on CFH immunolabeling indicate that CFH, which is normally confined to the choriocapillaris, intercapillary pillars, and Bruch’s membrane, is decreased in both early AMD and geographic atrophy (Bhutto et al., 2011).”
BackgroundLuan, Y., & Yao, Y.-M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01302 · Cited by 418
“It was found that mCRP played a role in choroidal vascular dysfunction in AMD by influencing endothelial cell phenotypes in vitro and ex vivo (63).”
BackgroundParainflammation, Chronic Inflammation and Age-Related Macular Degeneration
Chen, M., & Xu, H. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ri0615-239r · Cited by 381
“The expression of CFH [137], CD46, and CD59 [138]”
BackgroundRisk factors and biomarkers of age-related macular degeneration
Lambert, N. G., Elshelmani, H., Singh, M. K., Mansergh, F. C., Wride, M. A., Padilla, M., Keegan, D., Hogg, R. E., & Ambati, B. K. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.04.003 · Cited by 367
“elevated levels of CRP, there is an increased interaction between CRP and CFH (Bhutto et al., 2011).”
InfluentialAging 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 250
“…instance, reports of significant imbalances in the localization of CRP and CFH showed that in AMD versus age-matched control eyes, immunoreactivity against CRP is significantly higher in the RPE/Bruch's membrane/choroid complex, whereas that against CFH is significantly lower (Bhutto et al., 2011).”
BackgroundThe Membrane Attack Complex in Aging Human Choriocapillaris
Mullins, R. F., Schoo, D. P., Sohn, E. H., Flamme‐Wiese, M. J., Workamelahu, G., Johnston, R. M., Wang, K., Tucker, B. A., & Stone, E. M. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.07.017 · Cited by 236
“Eyes with AMD exhibit increased C-reactive protein and decreased complement factor H, consistent with a choroidal AMD microenvironment that favors complement activation.(67) Choriocapillaris degeneration, whether due to MAC or some other source of injury, is notable in eyes with early AMD,(15) and morphometric studies…”
BackgroundWhitmore, S. S., Sohn, E. H., Chirco, K. R., Drack, A. V., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.11.005 · Cited by 223
“Bhutto and colleagues examined the distribution of CRP and CFH in macular tissue from AMD donor eyes versus age-matched control eyes, and found an inverse relationship between CRP and CFH levels in eyes with advanced AMD (Bhutto et al., 2011).”
BackgroundChirco, K. R., Sohn, E. H., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2016) · Eye · doi:10.1038/eye.2016.216 · Cited by 223
Marazita, M. C., Dugour, A. V., Marquioni‐Ramella, M. D., Figueroa, J. M., & Suburo, Á. M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.11.011 · Cited by 212
“Moreover, in human AMD donor eyes, immunoreactivity for CFH is reduced compared to that found in age-matched controls [85].”
Ebrahimi, K. B., Callaway, N. F., Cano, M., & Handa, J. T. (2012) · The Journal of Pathology · doi:10.1002/path.4128 · Cited by 138
Mechanism of Inflammation in Age-Related Macular Degeneration
Parmeggiani, F., Romano, M., Costagliola, C., Semeraro, F., Incorvaia, C., D’Angelo, S., Perri, P., Palma, P. D., Nadai, K. D., & Sebastiani, A. (2012) · Mediators of Inflammation · doi:10.1155/2012/546786 · Cited by 140
McLeod, D. S., Bhutto, I. A., Edwards, M. M., Silver, R. E., Seddon, J. M., & Lutty, G. A. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20049 · Cited by 107
Self-citationThe eye as a complement dysregulation hotspot
Clark, S. J., & Bishop, P. N. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0649-6 · Cited by 106
“There is also increased deposition of C-reactive protein (CRP) deposition in the choriocapillaris in AMD [60, 72].”
BackgroundPentraxins in Complement Activation and Regulation
Ma, Y. J., & Garred, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03046 · Cited by 103
Regulation of the Complement System by Pentraxins
Haapasalo, K., & Meri, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01750 · Cited by 106
Nita, M., Grzybowski, A. E., Ascaso, F. J., & Huerva, V. (2014) · Mediators of Inflammation · doi:10.1155/2014/930671 · Cited by 128
“The complement system is a specific biochemical cascade and an integral element of inborn (not specific) immunological response, which supports (complements) the host antibodies ability to destroy pathogens, promotes removal of apoptotic cells and immune complexes, and enhances an individual…”
BackgroundIncreased choroidal mast cells and their degranulation in age-related macular degeneration
Bhutto, I. A., McLeod, D. S., JING, T. Y., Sunness, J. S., Seddon, J. M., & Lutty, G. A. (2016) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2015-308290 · Cited by 95
Self-citationKokkinopoulos, I., Colman, A., Hogg, C. R., Heckenlively, J., & Jeffery, G. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.04.014 · Cited by 90
“…was the chosen target for a read out of mitochondrial changes because of its critical role in outer retinal function (Boulton et al., 2004; Boulton and Dayhaw-Barker, 2001; Impact Publication(s) Protection of the retina from light-induced photoreceptor degeneration (Albarracin et al.,…”
Zarubina, A. V., Neely, D. C., Clark, M. E., Huisingh, C., Samuels, B. C., Zhang, Y., McGwin, G., Owsley, C. J., & Curcio, C. A. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2015.12.034 · Cited by 88
Lipécz, Á., Miller, L. R., Kovács, I., Czakó, C. N., Csípő, T., Baffi, J., Csiszár, A., Tarantini, S., Ungvari, Z. I., Yabluchanskiy, A., et al. (2019) · GeroScience · doi:10.1007/s11357-019-00138-3 · Cited by 88
Inflammation and retinal degenerative diseases
Kaur, G., & Singh, N. K. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.350192 · Cited by 90
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Owsley, C. J., Huisingh, C., Jackson, G. R., Curcio, C. A., Szalai, A. J., Dashti, N., Clark, M. E., Rookard, K., McCrory, M. A., Wright, T. T., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14502 · Cited by 70
Joseph, K., Kulik, L. N., Coughlin, B. A., Kunchithapautham, K., Bandyopadhyay, M., Thiel, S., Thielens, N. M., Holers, V. M., & Rohrer, B. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.421891 · Cited by 67
“If we acknowledge that oxidative stress is the earliest event leading to AMD,which known cell surface modification generated by oxidative stress could then be recognized by either pattern recognition molecules of the complement cascade or natural antibodies? Ligands might include, but are not restricted to, the follow…”
BackgroundA Revised Hemodynamic Theory of Age-Related Macular Degeneration
Gelfand, B. D., & Ambati, J. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.06.009 · Cited by 65
“Moreover, AMD pathologic features such as deposition of complement-related proteins, C-reactive protein, and advanced glycation end products demonstrate a punctate distribution in the RPE and Bruch's membrane that spatially correlates with the spaces between the vessels of the choriocapillaris, even in unaffected eyes…”
BackgroundMechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks
Parmeggiani, F., Sorrentino, F. S., Romano, M. R., Costagliola, C., Semeraro, F., Incorvaia, C., D’Angelo, S., Perri, P., Nadai, K. D., Roversi, E. B., et al. (2013) · Mediators of Inflammation · doi:10.1155/2013/435607 · Cited by 64
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“A similar study aimed to determine differences in total CRP levels in the retina based on AMD status (52).”
BackgroundMonomeric C‐reactive protein and inflammation in age‐related macular degeneration
Chirco, K. R., Whitmore, S. S., Wang, K., Potempa, L. A., Halder, J. A., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2016) · The Journal of Pathology · doi:10.1002/path.4766 · Cited by 59
“Due to its localization around the choriocapillaris, and its association with neovascular AMD [30], we assessed the effect of mCRP on choroidal endothelial cell migration.”
BackgroundInfluentialRomero‐Vázquez, S., Llorens, V., Soler-Boronat, A., Figueras‐Roca, M., Adán, A., & Molins, B. (2021) · Biomedicines · doi:10.3390/biomedicines9070763 · Cited by 56
“compared to age‐matched control individuals [100].”
Age‐related macular degeneration: A disease of extracellular complement amplification
de Jong, S., Tang, J., & Clark, S. J. (2022) · Immunological Reviews · doi:10.1111/imr.13145 · Cited by 54
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“Reduced expression of FH and CD46 by RPE cells is observed in AMD, and this coincides with increased deposition of the MAC and cell lysis [132,133].”
BackgroundInteraction of Complement Factor H and Fibulin3 in Age-Related Macular Degeneration
Wyatt, M. K., Tsai, J.-Y., Mishra, S., Campos, M. M., Jaworski, C. J., Fariss, R. N., Bernstein, S. L., & Wistow, G. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068088 · Cited by 42
Age-Related Macular Degeneration: A Disease of Systemic or Local Complement Dysregulation?
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C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration
Molins, B., Romero‐Vázquez, S., Fuentes‐Prior, P., Adán, A., & Dick, A. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00808 · Cited by 43
“Most notably, these authors found an inverse relationship between CRP and FH levels in macular tissue from patients with advanced AMD as compared to age-matched control individuals (86).”
ResultKeenan, T. D. L., Toso, M., Pappas, C. M., Nichols, L., Bishop, P. N., & Hageman, G. S. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-17009 · Cited by 41
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Schäfer, N., Grosche, A., Reinders, J., Hauck, S. M., Pouw, R. B., Kuijpers, T. W., Wouters, D., Ehrenstein, B. P., Enzmann, V., Zipfel, P. F., et al. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00542 · Cited by 36
“Reduced FH concentrations in stressed RPE and the detection of FHR-3 produced by macrophages in the damaged retina suggested a local shift of the FHR-3/FH equilibrium in retinal degeneration (71, 72).”
BackgroundJensen, E. G., Jakobsen, T. S., Thiel, S., Askou, A. L., & Corydon, T. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249752 · Cited by 40
“This is consistent with the findings of reduced levels of FH in Bruch’s membrane, CC, and the choroid of AMD specimens compared to controls [125] (Figure 4C).”
BackgroundResultAsian age-related macular degeneration: from basic science research perspective
Yanagi, Y., Foo, V. H. X., & Yoshida, A. (2018) · Eye · doi:10.1038/s41433-018-0225-x · Cited by 35
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Self-citationBruch’s Membrane and the Choroid in Age-Related Macular Degeneration
Edwards, M., & Lutty, G. A. (2021) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-66014-7_4 · Cited by 32
Self-citationHuisingh, C., McGwin, G., Neely, D. C., Zarubina, A. V., Clark, M. E., Zhang, Y., Curcio, C. A., & Owsley, C. J. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18316 · Cited by 30
“Information on a number of factors was compared between those participants with and without SDD. Consistent with previous work, the presence of SDD was associated with older age and higher levels of plasma CRP.22,46 The present study found no sex differences by SDD status, agreeing with some studies21 but disagreeing…”
ResultA role for mast cells in geographic atrophy
Ogura, S., Baldeosingh, R., Bhutto, I. A., Kambhampati, S. P., McLeod, D. S., Edwards, M. M., Rais, R., Schubert, W., & Lutty, G. A. (2020) · The FASEB Journal · doi:10.1096/fj.202000807r · Cited by 30
Self-citationIs Age-Related Macular Degeneration a Microvascular Disease?
Mullins, R. F., Khanna, A., Schoo, D. P., Tucker, B. A., Sohn, E. H., Drack, A. V., & Stone, E. M. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3209-8_36 · Cited by 30
Adamus, G. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.01.005 · Cited by 28
“The increased levels of CRP in eyes with early AMD may be an indication of local inflammation and cellular injury in the RPE–choroid layer [75].”
BackgroundInfluentialMast Cell-Derived Tryptase in Geographic Atrophy
McLeod, D. S., Bhutto, I. A., Edwards, M. M., Gedam, M., Baldeosingh, R., & Lutty, G. A. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22989 · Cited by 28
Self-citationSwinkels, M., Zhang, J. H., Tilakaratna, V., Black, G. C. M., Perveen, R., McHarg, S., Inforzato, A., Day, A. J., & Clark, S. J. (2018) · Scientific Reports · doi:10.1038/s41598-017-18395-7 · Cited by 30
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“FH is present in soft drusen in early AMD; however, choroidal FH levels are significantly lower in early AMD than in age-matched healthy controls [14,15], implying that reduced availability of FH locally in the choroid may contribute to AMD pathogenesis.”
BackgroundMethodRheohaemapheresis in the treatment of nonvascular age-related macular degeneration
Blaha, M., Rencová, E., Langrová, H., Studnička, J., Blaha, V., Rozsival, P., Lánská, M., & Sobotka, L. (2013) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2012.10.023 · Cited by 26
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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
Clinicopathologic Findings in Three Siblings With Geographic Atrophy
Edwards, M. M., McLeod, D. S., Shen, M., Grebe, R. R., Sunness, J. S., Bhutto, I. A., McDonnell, E., Pado, A. M., Gregori, G., Rosenfeld, P. J., et al. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.3.2 · Cited by 24
Self-citationZhang, P., Zhu, M., Geng-Spyropoulos, M., Shardell, M. D., González‐Freire, M., Gudnason, V. G., Eiríksdóttir, G., Schaumberg, D. A., Eyk, J. E. V., Ferrucci, L., et al. (2016) · PROTEOMICS · doi:10.1002/pmic.201600237 · Cited by 24
“AMD is characterized by localized inflammation and the presence of multiple proteins associated with complement, complement activation and regulation, and inflammatory proteins in drusen and the retinal pigment epithelium, Bruch’s membrane, and choriocapillaris [21, 22].”
Molecular Imaging of Retinal Disease
Capozzi, M. E., Gordon, A. Y., Penn, J. S., & Jayagopal, A. (2013) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2012.0279 · 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
“Similarly, the reduction of local CFH expression in the choriocapillaris and Bruch’s membrane of AMD donor eyes (Bhutto et al., 2011) also suggested that a reduction of local complement regulator expression might be associated with AMD pathogenesis.”
BackgroundRomero‐Vázquez, S., Adán, A., Figueras‐Roca, M., Llorenç, V., SLEVIN, M. A., Vilahur, G., Badimón, L., Dick, A. D., & Molins, B. (2020) · Aging · doi:10.18632/aging.103655 · Cited by 22
Mannes, M., Dopler, A., Huber-Lang, M. S., & Schmidt, C. Q. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.596415 · Cited by 23
Zhang, Y., Huang, Q. B., Tang, M., Zhang, J., & Fan, W. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129945 · Cited by 20
Kovacs, K. D., Ciulla, T. A., & Kiss, S. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2121646 · Cited by 20
Chirco, K. R., Flamme‐Wiese, M. J., Wiley, J. S., Potempa, L. A., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2018) · Eye · doi:10.1038/s41433-018-0170-8 · Cited by 17
Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress
Cui, X., Buonfiglio, F., Pfeiffer, N., & Gericke, A. (2024) · Biomedicines · doi:10.3390/biomedicines12040817 · Cited by 16
“…the pro-inflammatory upregulation of the CCL2-CCR2 axis, which is one of the major chemokine signaling pathways, and genetic ablation of CCL2 reduces age-related inflammatory changes in the choroid, reducing the recruitment of pro-inflammatory myeloid cells and attenuating CNV [72]. atrophy [71].”
BackgroundChen, R. C., Palestine, A. G., Lynch, A. M., Patnaik, J. L., Wagner, B. D., Mathias, M. T., & Mandava, N. (2021) · Translational Vision Science & Technology · doi:10.1167/tvst.10.12.7 · Cited by 16
Baicalin Attenuates Laser-Induced Choroidal Neovascularization
Yang, S. J., Jo, H., Kim, J.-G., & Jung, S. H. (2014) · Current Eye Research · doi:10.3109/02713683.2013.868908 · Cited by 15
Liu, Y. (2019) · International Journal of Ophthalmology · doi:10.18240/ijo.2019.03.17 · Cited by 13
Kubicka‐Trząska, A., Żuber-Łaskawiec, K., Dziedzina, S., Sanak, M., Romanowska‐Dixon, B., & Karska‐Basta, I. (2022) · Medicina · doi:10.3390/medicina58050658 · Cited by 15
Gurubaran, I. S., Heloterä, H., Marry, S., Koskela, A. K. J., Hyttinen, J. M. T., Paterno, J. J., Urtti, A. O., Chen, M., Xu, H., Kauppinen, A., et al. (2021) · Biology · doi:10.3390/biology10070622 · Cited by 13
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
Mitochondrial damage and clearance in retinal pigment epithelial cells
Gurubaran, I. S. (2024) · Acta Ophthalmologica · doi:10.1111/aos.16661 · Cited by 11
CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration
Lim, R. R., Shirali, S., Rowlan, J. S., Engel, A. L., Nazario, M., Gonzalez, K., Tong, A., Jay Neitz, A., Neitz, M., & Chao, J. R. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.4.43 · Cited by 10
Nomura, Y., Takahashi, H., Fujino, Y., Kawashima, H., & Yanagi, Y. (2015) · Retina · doi:10.1097/iae.0000000000000668 · Cited by 10
Multimeric Stability of Human C-reactive Protein in Archived Specimens
Li, Q., Kang, T., Tian, X., Ma, Y., Li, M., Richards, J. C., Bythwood, T., Wang, Y., Li, X., Liu, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058094 · Cited by 10
Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies
Bhandari, S. K., Lee, S., & Kim, H. J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010202 · Cited by 10
“The common CFH Y402H polymorphism impairs the regulatory function of CFH, promoting sustained complement activation and chronic inflammation [61,62].”
α1‐antitrypsin and C‐reactive protein levels in tear fluid after continuous contact lens wear
Barrett, A., Gnehm, D., Jones, J., & Trask, B. C. (2013) · Clinical and Experimental Optometry · doi:10.1111/cxo.12093 · Cited by 9
“Although Creactive protein has been observed to increase in other ocular tissues, such as the retina in association with age-related macular degeneration, to the best of our knowledge this is the first report of C-reactive protein in tear fluid.(28) Unlike previous studies that inventoried tear fluid components using…”
ResultRodrigo, F., Ruiz‐Moreno, J. M., García, J. B., Quesada, M. E. T., Segura, J., & Pinero, D. P. (2017) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_488_17 · Cited by 9
Mullins, R. F., Flamme‐Wiese, M. J., Navratil, E., Boese, E. A., Varzavand, K., Riker, M. J., Wang, K., Stone, E. M., & Tucker, B. A. (2024) · Experimental Eye Research · doi:10.1016/j.exer.2024.110128 · Cited by 8
Abdolrahimzadeh, S., Zweifel, S. A., Pippo, M. D., Bajka, A., Scuderi, G., & Lotery, A. J. (2023) · Eye · doi:10.1038/s41433-023-02654-1 · Cited by 8
“Complement system components are also localised in the eye [31] and the domains around CC endothelial cells are reported as the principal sites of membrane attack complexes in the macula, thus, the site of the highest complement-mediated stress possibly indicating vascular injury and choroidal impairment as a patholog…”
BackgroundMa, W., Paik, D. C., & Barile, G. R. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14352 · Cited by 8
Fernández‐Robredo, P., Recalde, S., Hernández, M., Zarranz‐Ventura, J., Molins, B., Casaroli-Marano, R. P., Adán, A., Sáenz-de-Viteri, M., & García‐Layana, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01862 · Cited by 7
“Finally, some authors have found significantly higher CRP deposits in the Bruch’s membrane and retinal and choroid vessels of wet AMD eyes compared to aged controls and AMD human donors (38).”
BackgroundTargeted Gene Candidates for Treatment and Early Diagnosis of Age‐Related Macular Degeneration
Çinici, E., Çağlar, Ö., Arslan, M. E., Dilekmen, N., Utlu, B., Mardinoğlu, A., & Türkez, H. (2021) · BioMed Research International · doi:10.1155/2021/6620900 · Cited by 7
“High levels of CRP are considered a risk for heart conditions, type II diabetes, and AMD [41].”
BackgroundMethodGlial remodeling and choroidal vascular pathology in eyes from two donors with Choroideremia
Edwards, M. M., McLeod, D. S., Grebe, R. R., Bhutto, I. A., Dahake, R., Crumley, K. M., & Lutty, G. A. (2022) · Frontiers in Ophthalmology · doi:10.3389/fopht.2022.994566 · Cited by 7
Self-citationSerum Inflammatory Markers After Rupture Retinal Laser Injury in Mice
Paulus, Y. M., Kuo, C.-H., Morohoshi, K., Nugent, A. K., Luo, Z., Nomoto, H., Blumenkranz, M. S., Palanker, D., & Ono, S. J. (2015) · Ophthalmic surgery, lasers & imaging retina · doi:10.3928/23258160-20150323-11 · Cited by 7
Risk Factors for Age-related Macular Degeneration
Berrow, E. J., Bartlett, H. E., Eperjesi, F., Gibson, J. M., Lecturer, S., Lecturer, S., & Heart of England NHS Trust, B. (2011) · European Ophthalmic Review · doi:10.17925/eor.2011.05.02.143 · Cited by 6
“There is evidence that choroidal circulation attenuation may be responsible for development of ARMD.”
BackgroundInfluentialNizawa, T., Bhutto, I. A., Tiwari, A., Grebe, R. R., Alt, J., Rais, R., Edwards, M. M., & Lutty, G. A. (2021) · Translational Vision Science & Technology · doi:10.1167/tvst.10.14.37 · Cited by 6
Self-citationYoon, B. W., Lee, Y., & Seo, J. H. (2024) · Biomedicines · doi:10.3390/biomedicines12040807 · Cited by 8
Priorities and trends in the study of proteins in eye research, 1924–2014
Semba, R. D., Lam, M. P. Y., Sun, K., Zhang, P., Schaumberg, D. A., Ferrucci, L., Ping, P., & Eyk, J. E. V. (2015) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201500006 · Cited by 5
“Neutralization of VEGF-A with ranibizumab, a recombinant monoclonal antibody, was shown to prevent visual loss in neovascular AMD [19].”
BackgroundInfluentialElevation of Granulocyte Colony Stimulating Factor in Human AMD Donor RPE-Choroid
Mulfaul, K., Khan, A. H., Schwarte, S. G., Voigt, A. P., Moore, R. F., Potempa, L. A., Wang, K., Scheetz, T. E., Stone, E. M., Tucker, B. A., et al. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.14.15 · Cited by 5
Swan, J., Toomey, C. B., Bergstrand, M., Cuello, H., Robie, J., Yu, H., Yuan, Y. H., Kooner, A. S., Chen, X., Shaughnessy, J., et al. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.6.81 · Cited by 5
Huang, X., Zhang, L., Fu, Y., Zhang, M., Yang, Q., & Peng, J. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1199922 · Cited by 5
“stimulate inflammatory response and C-reactive protein, and local inflammation caused by abnormal RPE will aggravate drusen aggregation (Bhutto et al., 2011).”
Background
Metadata
- Authors
- Bhutto, I. A., Baba, T., Merges, C., Juriasinghani, V., McLeod, D. S., & Lutty, G. A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Lutty, G. A.
- Venue
- British Journal of Ophthalmology
- Publisher
- BMJ
- Published
- 2011-06-01
- Volume
- 95
- Issue
- 9
- Pages
- 1323-1330
- ISSN
- 0007-1161 (ISSN-L)
- PMC
- PMC4916773
- OpenAlex
- W1974343663
- Cited by
- 126
- References
- 34
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 11 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 15 · 2015: 9 · 2014: 13 · 2013: 9 · 2012: 5
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Johns Hopkins University
- National Eye Institute (R01EY016151, #EY01765, P30EY001765)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- age-related macular degeneration, C-reactive protein, complement factor H, complement activation, retinal inflammation, choroid, Bruch's membrane, choroidal stroma, drusen, retinal pigment epithelium, choriocapillaris, immunolocalization
- MeSH terms
- Aged, Aged, 80 and over, Aging, C-Reactive Protein, Female, Humans, Immunohistochemistry, Macular Degeneration, Male, Prognosis, Biomarkers, Complement Factor H, Disease Progression, Retinal Pigment Epithelium
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