High Myopia and the Complement System: Factor H in Myopic Maculopathy

Abstract

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 > 26 mm), low myopia (axial length 23.5–25.9 mm) and control (axial length ˂ 23.4 mm). The degree of maculopathy was classified according to fundus oculi findings following IMI’s 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 ˂ 0.05). Significantly high CFH values were found in those eyes with choroid atrophy and neovascularization (p ˂ 0.05). In parallel, the CFH concentration correlated inversely with choroid thickness (R = −0.624). CFD levels did not correlate with maculopathy. All the obtained data seem to suggest that CFH plays a key role in myopic pathology.

Next-Generation Sequencing Screening of 43 Families with Non-Syndromic Early-Onset High Myopia: A Clinical and Genetic Study

“…In the last few years, various researchers have tried to link EoHM to changes in CFH. In 2021, García-Gen et al established the key role of CFH in the development of myopic disease [63]. In our study, there was a variant in this gene in OFT-00097.…”

Widespread Involvement of Acetylation in the Retinal Metabolism of Form-Deprivation Myopia in Guinea Pigs

“…Riddell et al examined gene expression in experimentally myopic chicks using RNA sequencing and meta-analysis successively and found transcriptional activation associated with the immune and complement systems. , Giummarra et al suggested that significant upregulation of the complement and coagulation cascade pathways during the induction of form-deprivation myopia may be related to physiological stress mechanisms associated with choroidal contraction and reduced blood flow . Subsequently, García-Gen et al demonstrated the correlation between the level of complement factor H (CFH) in aqueous humor and myopic choroidal atrophy in patients with high myopia . Thus, our results confirm the activation of the complement system in the myopic retina at the protein level, which may be associated with decreased choroidal blood flow and atrophy in myopic eyes; however, additional molecular and cellular experiments are needed to confirm this finding.…”

Evaluating the clinical utility of measuring levels of factor H and the related proteins

“…So far, FHRs haven't been reported for vitreous, aqueous humor, or tears, but this could be of major interest. Lastly, the role of the complement system has been implicated in various other ocular diseases namely autoimmune uveitis, glaucoma, and diabetes retinopathy and myopia, but the involvement of the FH protein family has thus far not been investigated (Bansal and Gupta, 2020;Clark and Bishop, 2018;Fiedorowicz et al, 2021;García-Gen et al, 2021;Gui et al, 2020;Jha et al, 2007;Rajagopal et al, 2021;Sundstrom et al, 2018;Torok et al, 2013;Youngblood et al, 2019;Zhang et al, 2020).…”