Abnormal pigment epithelium-derived factor processing in progressive myopia

Минкевич, Н. И.; Morozova‐Roche, Ludmilla A.; Iomdina, Elena N.; Rakitina, Tatiana V.; Bogachuk, A. P.; Kakuev, Dmitry L.; Smirnova, Evgeniya V.; Бабиченко, И. И.; Липкин, В. М.

doi:10.1016/j.exer.2016.08.017

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…High myopia and developing myopic maculopathy are associated with an altered expression of vascular endothelial growth factors (VEGF) and pigment epithelium-derived (growth) factor (PEDF) [34][35][36], and with a higher regulation of hypoxia-induced factors [37]. In pathologic myopia, high C3a levels have been described in the plasma of patients with choroid angiogenesis compared to normal controls, which suggests an interaction between innate immunity and choroid angiogenesis [35,38].…”

Section: Discussionmentioning

confidence: 99%

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

García-Gen

Penadés

Mérida

et al. 2021

JCM

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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.

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Section: Discussionmentioning

confidence: 99%

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

García-Gen

Penadés

Mérida

et al. 2021

JCM

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“…The PEDF levels in Tenon's capsule of myopes were investigated. The level of "soluble" 45 kDa PEDF was reduced by twofold in Tenon's capsules of high myopia patients while the content of the "insoluble" 50 kDa form of PEDF was increased by fourfold [99]. This result indicated that abnormal metabolism rather than the decrease in PEDF synthesis might be correlated with myopia development.…”

Section: Pedf Levels In Patients With Cnv Secondary To Pathological Mmentioning

confidence: 85%

Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization

2020

Oxidative Medicine and Cellular Longevity

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Choroidal neovascularization (CNV) is a sight-threatening disease and is characterized by the formation of pathological neovascularization in the choroid which extends into the subretinal space. Exudative age-related macular degeneration (AMD) is the formation of CNV in the macular area which leads to irreversible blindness. Continuous leakage and hemorrhage of the CNV lesion may eventually result in scarring or later fibrosis, which could result in photoreceptor cell atrophy. The current strategy for treating CNV is the use of antivascular endothelial growth factor (VEGF) agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF therapy. Other studies have also reported the side effects of single anti-VEGF treatment. And long-term inhibition of a single system may result in collateral damage to other visual elements. Pigment epithelium-derived factor (PEDF) is a 50 kDa protein that was first isolated from the conditioned medium of human RPE cells. PEDF has both antiangiogenesis and neuroprotective functions for photoreceptor cells. It may be a potential ocular antiangiogenic agent. This review outlines the distribution of PEDF in the eye, the mechanism of antiangiogenesis, the protective effect on the retina, and the relationship between PEDF and VEGF.

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“…The target pathways and their related molecular alterations can be broadly grouped as those related to scleral remodeling (matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) 7 ), active Bruch’s membrane elongation 9 (amphiregulin 10 ), inflammation (interleukin 6 (IL-6) 11,12 , and those related to vascular/atrophic changes (pigment epithelium derived factor (PEDF) 3,13 , vascular endothelial growth factor (VEGF), angiopoietin (Ang)) 3–5,8 . Angiopoietin, VEGF and PEDF are synthesized by retinal pigment epithelial cells and are vital for the maintenance of the choriocapillaris 14 .…”

Section: Introductionmentioning

confidence: 99%

Correlation of axial length and myopic macular degeneration to levels of molecular factors in the aqueous

Wong¹,

Yanagi²,

Tsai³

et al. 2019

Sci Rep

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To elucidate the molecular processes associated with the development of myopic macular degeneration (MMD), we measured the intraocular concentrations of molecular factors in emmetropic and myopic eyes. This is a retrospective clinic-based case-control study that included eyes undergoing routine cataract surgery whereby aqueous humour samples were obtained. We measured the concentrations of pigment epithelium derived factor(PEDF), matrix metalloproteinase 2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-2), vascular endothelial growth factor isoform A(VEGF-A), interleukin 8(IL-8), interleukin 6(IL-6), C-reactive protein(CRP), angiopoietin 2(Ang2), and amphiregulin. 38 eyes (axial length (AL): 22.4–32.4 mm), including 12 highly myopic (HM) eyes (AL ≥ 26.5 mm) without MMD and 12 HM eyes with MMD but without neovascularization were included. Eyes with MMD were found to have significantly lower VEGF-A levels (p = 0.007) and higher MMP-2 levels (p = 0.02) than control eyes after adjusting for age and gender. MMP-2 levels correlated positively (r = 0.58, p = 0.002), while VEGF-A levels correlated negatively with longer axial length (r = −0.75, p < 0.001). Both the concentrations of VEGF-A (P = 0.25) and MMP-2 (P = 0.69) were not significantly associated with MMD after adjusting for AL. These findings suggest that the predominant mechanism underlying the development of non-neovascular MMD may be axial elongation, driven in part by MMP-2 related mechanisms.

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Abnormal pigment epithelium-derived factor processing in progressive myopia

Cited by 4 publications

References 26 publications

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

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

Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization

Correlation of axial length and myopic macular degeneration to levels of molecular factors in the aqueous

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