RANTES (CCL5) in Patients With Geographic Atrophy Age-Related Macular Degeneration

Overview

Journal Transl Vis Sci Technol

Specialties Biomedical Engineering
Ophthalmology

Date 2023 Jan 12

PMID 36633873

Authors

Cheryl N Fonteh

Alan G Palestine

Brandie D Wagner

Jennifer L Patnaik

Marc T Mathias

Niranjan Manoharan

Naresh Mandava

Rebecca Baldermann

Talisa De Carlo

Anne M Lynch

Affiliations

Soon will be listed here.

Abstract

Purpose: A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls.

Methods: The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction.

Results: The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799-19,554] pg/mL vs. 5435 [3420-9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls.

Conclusions: We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients.

Translational Relevance: The biomarker RANTES is significantly lower in GA AMD patients compared to controls.

Citing Articles

Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy.

Rajeswaren V, Wagner B, Patnaik J, Mandava N, Mathias M, Manoharan N Front Ophthalmol (Lausanne). 2024; 4:1356957.

PMID: 38984140 PMC: 11182128. DOI: 10.3389/fopht.2024.1356957.

Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate.

de Carlo Forest T, Gill Z, Lisker-Cervantes A, Gnanaraj R, Grove N, Patnaik J Am J Ophthalmol. 2024; 264:168-177.

PMID: 38552931 PMC: 11257804. DOI: 10.1016/j.ajo.2024.03.023.

Chemokine Receptor Profile of T Cells and Progression Rate of Geographic Atrophy Secondary to Age-related Macular Degeneration.

Hinnerskov J, Krogh Nielsen M, Thomsen A, Steffensen M, Honore B, Vorum H Invest Ophthalmol Vis Sci. 2024; 65(1):5.

PMID: 38165703 PMC: 10768715. DOI: 10.1167/iovs.65.1.5.

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.

Rajeswaren V, Wagner B, Patnaik J, Mandava N, Mathias M, Manoharan N Transl Vis Sci Technol. 2023; 12(8):1.

PMID: 37526620 PMC: 10395651. DOI: 10.1167/tvst.12.8.1.

References

Shah D, Wanchu A, Bhatnagar A . Interaction between oxidative stress and chemokines: possible pathogenic role in systemic lupus erythematosus and rheumatoid arthritis. Immunobiology. 2011; 216(9):1010-7. DOI: 10.1016/j.imbio.2011.04.001. View

Mause S, von Hundelshausen P, Zernecke A, Koenen R, Weber C . Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol. 2005; 25(7):1512-8. DOI: 10.1161/01.ATV.0000170133.43608.37. View

Ferris 3rd F, Wilkinson C, Bird A, Chakravarthy U, Chew E, Csaky K . Clinical classification of age-related macular degeneration. Ophthalmology. 2013; 120(4):844-51. PMC: 11551519. DOI: 10.1016/j.ophtha.2012.10.036. View

Fritsche L, Igl W, Cooke Bailey J, Grassmann F, Sengupta S, Bragg-Gresham J . A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2015; 48(2):134-43. PMC: 4745342. DOI: 10.1038/ng.3448. View

Boger C, Fischereder M, Deinzer M, Aslanidis C, Schmitz G, Stubanus M . RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients. Atherosclerosis. 2005; 183(1):121-9. DOI: 10.1016/j.atherosclerosis.2005.03.006. View

de Jager S, Bongaerts B, Weber M, Kraaijeveld A, Rousch M, Dimmeler S . Chemokines CCL3/MIP1α, CCL5/RANTES and CCL18/PARC are independent risk predictors of short-term mortality in patients with acute coronary syndromes. PLoS One. 2012; 7(9):e45804. PMC: 3448678. DOI: 10.1371/journal.pone.0045804. View

Woldemussie E, Ruiz G, Wijono M, Wheeler L . Neuroprotection of retinal ganglion cells by brimonidine in rats with laser-induced chronic ocular hypertension. Invest Ophthalmol Vis Sci. 2001; 42(12):2849-55. View

Ridker P . C-reactive protein: eighty years from discovery to emergence as a major risk marker for cardiovascular disease. Clin Chem. 2008; 55(2):209-15. DOI: 10.1373/clinchem.2008.119214. View

Lynch A, Mandava N, Patnaik J, Frazer-Abel A, Wagner B, Palestine A . Systemic activation of the complement system in patients with advanced age-related macular degeneration. Eur J Ophthalmol. 2019; 30(5):1061-1068. DOI: 10.1177/1120672119857896. View

10.

Brown E, Lewin A, Ash J . Mitochondria: Potential Targets for Protection in Age-Related Macular Degeneration. Adv Exp Med Biol. 2018; 1074:11-17. DOI: 10.1007/978-3-319-75402-4_2. View

11.

Testelmans D, Tamisier R, Barone-Rochette G, Baguet J, Roux-Lombard P, Pepin J . Profile of circulating cytokines: impact of OSA, obesity and acute cardiovascular events. Cytokine. 2013; 62(2):210-6. DOI: 10.1016/j.cyto.2013.02.021. View

12.

de Ferranti S, Rifai N . C-reactive protein and cardiovascular disease: a review of risk prediction and interventions. Clin Chim Acta. 2002; 317(1-2):1-15. DOI: 10.1016/s0009-8981(01)00797-5. View

13.

Donoso L, Kim D, Frost A, Callahan A, Hageman G . The role of inflammation in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2006; 51(2):137-52. PMC: 4853913. DOI: 10.1016/j.survophthal.2005.12.001. View

14.

Cougnard-Gregoire A, Delyfer M, Korobelnik J, Rougier M, Malet F, Le Goff M . Long-term blood pressure and age-related macular degeneration: the ALIENOR study. Invest Ophthalmol Vis Sci. 2013; 54(3):1905-12. DOI: 10.1167/iovs.12-10192. View

15.

Lynch A, Patnaik J, Cathcart J, Mathias M, Siringo F, Echalier E . COLORADO AGE-RELATED MACULAR DEGENERATION REGISTRY: Design and Clinical Risk Factors of the Cohort. Retina. 2017; 39(4):656-663. DOI: 10.1097/IAE.0000000000002023. View

16.

Richard A, Duker J, Reichel E . Geographic atrophy: where we are now and where we are going. Curr Opin Ophthalmol. 2021; 32(3):247-252. DOI: 10.1097/ICU.0000000000000763. View

17.

Krogh Nielsen M, Subhi Y, Molbech C, Falk M, Nissen M, Sorensen T . Chemokine Profile and the Alterations in CCR5-CCL5 Axis in Geographic Atrophy Secondary to Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2020; 61(4):28. PMC: 7401724. DOI: 10.1167/iovs.61.4.28. View

18.

Guymer R, Rosenfeld P, Curcio C, Holz F, Staurenghi G, Freund K . Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 4. Ophthalmology. 2019; 127(3):394-409. PMC: 7218279. DOI: 10.1016/j.ophtha.2019.09.035. View

19.

Sadda S, Guymer R, Holz F, Schmitz-Valckenberg S, Curcio C, Bird A . Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3. Ophthalmology. 2017; 125(4):537-548. PMC: 11366072. DOI: 10.1016/j.ophtha.2017.09.028. View

20.

Suffee N, Richard B, Hlawaty H, Oudar O, Charnaux N, Sutton A . Angiogenic properties of the chemokine RANTES/CCL5. Biochem Soc Trans. 2011; 39(6):1649-53. DOI: 10.1042/BST20110651. View