{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:47:13Z","timestamp":1778028433388,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>High myopia (HM) is both a medical problem and refractive error of the eye owing to excessive eyeball length, which progressively makes eye tissue atrophic, and is one of the main causes for diminishing visual acuity in developed countries. Despite its high prevalence and many genetic and proteomic studies, no molecular pattern exists that explain the degenerative process underlying HM, which predisposes patients to other diseases like glaucoma, cataracts, retinal detachment and chorioretinal atrophy that affect the macular area. To determine the relation between complement Factors H (CFH) and D (CFD) and the maculopathy of patients with degenerative myopia, we studied aqueous humor samples that were collected by aspiration from 122 patients during cataract surgery. Eyes were classified according to eyeball axial length as high myopia (axial length &gt; 26 mm), low myopia (axial length 23.5\u201325.9 mm) and control (axial length \u02c2 23.4 mm). The degree of maculopathy was classified according to fundus oculi findings following IMI\u2019s classification. Subfoveal choroid thickness was measured by optical coherence tomography. CFH and CFD measurements were taken by ELISA. CFH levels were significantly high in the high myopia group vs. the low myopia and control groups (p \u02c2 0.05). Significantly high CFH values were found in those eyes with choroid atrophy and neovascularization (p \u02c2 0.05). In parallel, the CFH concentration correlated inversely with choroid thickness (R = \u22120.624). CFD levels did not correlate with maculopathy. All the obtained data seem to suggest that CFH plays a key role in myopic pathology.<\/jats:p>","DOI":"10.3390\/jcm10122600","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T10:30:25Z","timestamp":1623666625000},"page":"2600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High Myopia and the Complement System: Factor H in Myopic Maculopathy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-9266","authenticated-orcid":false,"given":"Enrique","family":"Garc\u00eda-Gen","sequence":"first","affiliation":[{"name":"Departamento Ciencias Biom\u00e9dicas, Universidad CEU Cardenal Herrera, CEU Universities, 46115 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Penad\u00e9s","sequence":"additional","affiliation":[{"name":"Departamento Ciencias Biom\u00e9dicas, Universidad CEU Cardenal Herrera, CEU Universities, 46115 Valencia, Spain"},{"name":"Thematic Cooperative Health Network for Research in Ophthalmology (Oftared), Carlos II Health Institute, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"M\u00e9rida","sequence":"additional","affiliation":[{"name":"Departamento Ciencias Biom\u00e9dicas, Universidad CEU Cardenal Herrera, CEU Universities, 46115 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-7847","authenticated-orcid":false,"given":"Carmen","family":"Desco","sequence":"additional","affiliation":[{"name":"Departamento Ciencias Biom\u00e9dicas, Universidad CEU Cardenal Herrera, CEU Universities, 46115 Valencia, Spain"},{"name":"Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunidad Valenciana (FISABIO), 46020 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Araujo-Miranda","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunidad Valenciana (FISABIO), 46020 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-5370","authenticated-orcid":false,"given":"Amparo","family":"Navea","sequence":"additional","affiliation":[{"name":"Departamento Ciencias Biom\u00e9dicas, Universidad CEU Cardenal Herrera, CEU Universities, 46115 Valencia, Spain"},{"name":"Thematic Cooperative Health Network for Research in Ophthalmology (Oftared), Carlos II Health Institute, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-9230","authenticated-orcid":false,"given":"F.","family":"Bosch-Morell","sequence":"additional","affiliation":[{"name":"Departamento Ciencias Biom\u00e9dicas, Universidad CEU Cardenal Herrera, CEU Universities, 46115 Valencia, Spain"},{"name":"Thematic Cooperative Health Network for Research in Ophthalmology (Oftared), Carlos II Health Institute, 28029 Madrid, Spain"},{"name":"Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunidad Valenciana (FISABIO), 46020 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0161-6420(79)35466-5","article-title":"Physiologic vs Pathologic Myopia: Genetics vs Environment","volume":"86","author":"Curtin","year":"1979","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.preteyeres.2015.12.001","article-title":"Updates of pathologic myopia","volume":"52","author":"Lai","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.oftal.2016.11.016","article-title":"Bio-environmental factors associated with myopia: An updated review","volume":"92","author":"Galvis","year":"2017","journal-title":"Arch. Soc. Esp. Oftalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.ophtha.2016.01.006","article-title":"Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050","volume":"123","author":"Holden","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0161-6420(01)01024-7","article-title":"Prevalence and progression of myopic retinopathy in an older population","volume":"109","author":"Vongphanit","year":"2002","journal-title":"Ophthalmology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.preteyeres.2017.09.004","article-title":"The epidemics of myopia: Aetiology and prevention","volume":"62","author":"Morgan","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","unstructured":"Points, K. (2020). Updates on Myopia. Updates Myopia, 27\u201351."},{"key":"ref_8","first-page":"415","article-title":"Pathologic myopia","volume":"6","year":"2016","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.ophtha.2009.11.003","article-title":"Long-term Pattern of Progression of Myopic Maculopathy: A Natural History Study","volume":"117","author":"Hayashi","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_10","first-page":"99","article-title":"Posterior staphyloma in pathologic myopia","volume":"70","author":"Jonas","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ajo.2008.03.010","article-title":"Clinical Characteristics of Posterior Staphyloma in Eyes with Pathologic Myopia","volume":"146","author":"Hsiang","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1073\/pnas.1814014116","article-title":"Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice","volume":"116","author":"Landowski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7227","DOI":"10.1073\/pnas.0501536102","article-title":"A Common Haplotype in the Complement Regulatory Gene Factor H (HF1CFH) Predisposes Individuals to Age-Related Macular Degeneration","volume":"102","author":"Hageman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1126\/science.1110189","article-title":"Complement Factor H Polymorphism and Age-Related Macular Degeneration","volume":"308","author":"Edwards","year":"2005","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"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., and Mayne, S.T. (2014). Complement Factor H Polymorphism in Age-Related Macular Degeneration. Science, 385.","DOI":"10.1126\/science.1109557"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Clark, S.J., Bishop, P.N., and Day, A.J. (2010). Complement factor H and age-related macular degeneration: The role of glycosaminoglycan recognition in disease pathology. Biochem. Soc. Trans.","DOI":"10.1042\/BST0381342"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1016\/j.ophtha.2006.02.049","article-title":"Complement Factor H Increases Risk for Atrophic Age-Related Macular Degeneration","volume":"113","author":"Postel","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"McHarg, S., Clark, S.J., Day, A.J., and Bishop, P.N. (2015). Age-related macular degeneration and the role of the complement system. Mol. Immunol.","DOI":"10.1016\/j.molimm.2015.02.032"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molimm.2004.02.005","article-title":"The human complement factor H: Functional roles, genetic variations and disease associations","volume":"41","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_20","first-page":"227","article-title":"The Compliment System","volume":"343","author":"Sarma","year":"2012","journal-title":"NIH Public Access Author Manuscr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/ni.3858","article-title":"Novel mechanisms and functions of complement","volume":"18","author":"Hajishengallis","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Toomey, C.B., Johnson, L.V., and Bowes Rickman, C. (2018). Complement factor H in AMD: Bridging genetic associations and pathobiology. Prog. Retin. Eye Res., 62.","DOI":"10.1016\/j.preteyeres.2017.09.001"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1475-1313.2011.00875.x","article-title":"Visual guidance of recovery from lens-induced myopia in tree shrews (Tupaia glis belangeri)","volume":"32","author":"Amedo","year":"2012","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3109\/15569520903178364","article-title":"Illumination with monochromatic long-wavelength light promotes myopic shift and ocular elongation in newborn pigmented guinea pigs","volume":"28","author":"Long","year":"2009","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_25","first-page":"675","article-title":"Complement factors C1q, C3 and C5b-9 in the posterior sclera of guinea pigs with negative lens-defocused myopia","volume":"8","author":"Gao","year":"2015","journal-title":"Int. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ebiom.2016.07.021","article-title":"Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation","volume":"10","author":"Lin","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ikeda, S., Kurihara, T., Toda, M., and Jiang, X. (2020). Oral Bovine Milk Lactoferrin Administration Suppressed Myopia Development through Matrix Metalloproteinase 2 in a Mouse Model, 1\u20139. Nutrients, 12.","DOI":"10.3390\/nu12123744"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0042-6989(62)90039-1","article-title":"Correlation ametropia and component ametropia","volume":"2","author":"Sorsby","year":"1962","journal-title":"Vis. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1038\/s41467-018-03649-3","article-title":"CCDC102B confers risk of low vision and blindness in high myopia","volume":"9","author":"Hosoda","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"M20","DOI":"10.1167\/iovs.18-25957","article-title":"IMI-Defining and Classifying Myopia: A Proposed Set of Standards for Clinical and Epidemiologic Studies","volume":"60","author":"Flitcroft","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1126\/science.1110359","article-title":"Complement factor H variant increases the risk of age-related macular degeneration","volume":"308","author":"Haines","year":"2005","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fisher, D.E., Klein, B.E.K., Wong, T.Y., Rotter, J.I., Li, X., Shrager, S., Burke, G.L., Klein, R., and Cotch, M.F. (2016). Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population the Multi-Ethnic Study of Atherosclerosis. Ophthalmology.","DOI":"10.1016\/j.ophtha.2015.12.026"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1167\/iovs.05-1655","article-title":"Complement factor H: Spatial and temporal expression and localization in the eye","volume":"47","author":"Mandal","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2016.08.017","article-title":"Abnormal pigment epithelium-derived factor processing in progressive myopia","volume":"152","author":"Minkevich","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Long, Q., Cao, X., Bian, A., and Li, Y. (2016). C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/6958752"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, W., Guan, Y., He, G., Li, Z., Song, H., Xie, S., and Han, Q. (2015). Aqueous Levels of Pigment Epithelium-Derived Factor and Macular Choroidal Thickness in High Myopia. J. Ophthalmol., 2015.","DOI":"10.1155\/2015\/731461"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E7091","DOI":"10.1073\/pnas.1721443115","article-title":"Scleral hypoxia is a target for myopia control","volume":"115","author":"Wu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9719","DOI":"10.1038\/s41598-017-10277-2","article-title":"Novel evidence for complement system activation in chick myopia and hyperopia models: A meta-analysis of transcriptome datasets","volume":"7","author":"Riddell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.exer.2017.03.004","article-title":"Metabolic characterization of human aqueous humor in relation to high myopia","volume":"159","author":"Ji","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ji, Y., Rong, X., and Lu, Y. (2018). Metabolic characterization of human aqueous humor in the cataract progression after pars plana vitrectomy. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0729-y"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ryoo, N.K., Ahn, S.J., Park, K.H., Ahn, J., Seo, J., Han, J.W., Kim, K.W., and Woo, S.J. (2018). Thickness of retina and choroid in the elderly population and its association with Complement Factor H polymorphism: KLoSHA Eye study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209276"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fimmu.2020.00154","article-title":"A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy","volume":"11","author":"Shahulhameed","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Francisco, B.M., Salvador, M., and Amparo, N. (2015). Oxidative stress in myopia. Oxidative Med. Cell. Longev.","DOI":"10.1155\/2015\/750637"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/0891-5849(95)02219-8","article-title":"Lipid peroxidation products in human subretinal fluid","volume":"20","author":"Sanz","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3341\/kjo.2016.30.3.172","article-title":"Oxidative Stress Levels in Aqueous Humor from High Myopic Patients","volume":"30","author":"Kim","year":"2016","journal-title":"Korean J. Ophthalmol.  KJO"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13873","DOI":"10.1038\/s41598-019-50420-9","article-title":"CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex","volume":"9","author":"Borras","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nature10449","article-title":"Complement factor H binds malondialdehyde epitopes and protects from oxidative stress","volume":"478","author":"Weismann","year":"2011","journal-title":"Nature"},{"key":"ref_48","first-page":"1","article-title":"Imbalance Between Oxidative Stress and Growth Factors in Human High Myopia","volume":"11","author":"Villar","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"49016","DOI":"10.18632\/oncotarget.14940","article-title":"Nitration of tyrosines in complement factor H domains alters its immunological activity and mediates a pathogenic role in age related macular degeneration","volume":"8","author":"Krilis","year":"2017","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.freeradbiomed.2018.09.034","article-title":"Dual roles of different redox forms of complement factor H in protecting against age related macular degeneration","volume":"129","author":"Krilis","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1093\/hmg\/ddl396","article-title":"CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses","volume":"15","author":"Conley","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8828","DOI":"10.1167\/iovs.11-7933","article-title":"Complement factor D in age-related macular degeneration","volume":"52","author":"Stanton","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kanan, Y., Siefert, J.C., Kinter, M., and Al-Ubaidi, M.R. (2014). Complement factor H, vitronectin, and opticin are tyrosine-sulfated proteins of the retinal pigment epithelium. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105409"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2174\/13894501113149990015","article-title":"Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases HHS Public Access","volume":"14","author":"Mitra","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.brainresrev.2009.09.006","article-title":"The role and regulation of hypoxia-inducible factor-1\u03b1 expression in brain development and neonatal hypoxic\u2013ischemic brain injury","volume":"62","author":"Fan","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kurihara, T., Westenskow, P.D., and Friedlander, M. (2014). Hypoxia-inducible factor (HIF)\/vascular endothelial growth factor (VEGF) signaling in the retina. Adv. Exp. Med. Biol.","DOI":"10.1007\/978-1-4614-3209-8_35"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/12\/2600\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:13:37Z","timestamp":1760163217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/12\/2600"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,12]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["jcm10122600"],"URL":"https:\/\/doi.org\/10.3390\/jcm10122600","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,12]]}}}