Hyperhomocysteinemia Causes Chorioretinal Angiogenesis with Placental Growth Factor Upregulation

Abstract

Hyperhomocysteinemia is a risk factor for atherosclerosis, which may also be associated with retinal vascular disease, diabetic retinopathy, retinal vein occlusion, and glaucoma. For this study, we established a hyperhomocysteinemia animal model to explore homocysteine (hcy)-related choroidal angiogenesis and possible related factors. We injected Sprague Dawley (SD) rats with different concentrations of hcy and performed color fundus imaging, fluorescein angiography, image-guided optical coherence tomography, and retinal histology to observe the retinal and choroidal changes. Subsequently, we observed prominent choroidal vasculature with congested and tortuous retinal and choroidal vessels in fundus angiographies of the hyperhomocysteinemia animal model. In the histological study, the choroidal capillaries proliferated in the hcy-treated eyes, mimicking choroidal neovascularization. Disrupted retinal pigment epithelium (RPE), abnormal branching vascular network (BVN), and polyp-like structures were also observed in the hcy-treated eyes. Furthermore, we found that placental growth factor (PlGF), but not vascular epithelial growth factor (VEGF), was the key mediating factor of this phenomenon. Our findings suggest that hyperhomocysteinemia might cause choroidal angiogenesis.

Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors

“…Besides VEGFA, HIF-1α can also induce the placental growth factor (PlGF) ( Zimna and Kurpisz, 2015 ; Charnock-Jones, 2016 ; Mitsui et al., 2018 ), an emerging target in retinal neovascular diseases ( Kwon and Jee, 2018 ; Lee et al., 2018 ; Saddala et al., 2018 ; Lazzara et al., 2019 ; Van Bergen et al., 2019 ). Furthermore, HIF-1α is involved in expression of several microRNAs (miRNAs), that are named HypoxamiRs if they bear in their promoter region the hypoxia responsive elements (HREs) ( Nallamshetty et al., 2013 ; Bertero et al., 2017 ).…”

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients

“…The results showed that the expression of serum PEDF and IL-12 in the study group was significantly lower than that in the control group, while the expression of serum Hcy and IL-4 was significantly higher than that in the control group, without significant difference in the expression of serum IFN-γ between the two groups. Hcy, a sulfur-containing amino acid that is highly expressed in glaucoma patients, can damage vascular endothelial cells of eyes through multiple pathways, and induce optic atrophy (19). PEDF can be produced in many parts of the eyes inhibiting angiogenesis, so the reduction in its expression significantly increases the number of new vessels in the eyes, thus promoting the progression of glaucoma (20).…”