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Abstract
Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium–choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.
Highlights
Licensee MDPI, Basel, Switzerland.Age-related macular degeneration (AMD) is one of the most common causes of visual impairment and sight loss in the elderly that may be irreversible
In this study we have examined the expression of Leucine-rich a-2-glycoprotein 1 (LRG1) in the choroidal neovascular membranes (CNVMs) and the aqueous humor of neovascular form of AMD (nvAMD) patients, in order to determine whether diseased retinal tissue is a source of LRG1, and if so, to ask whether treatment with vascular endothelial growth factor (VEGF) blockers has any impact on
In order to assess whether LRG1 is expressed in the blood vessels of Choroidal neovascular membranes (CNVMs) of nvAMD patients, appropriate specimens from an anti-VEGFA-naïve and a treated eye were collected during submacular surgery for retinal pigment epithelium–choroid graft transplantation and immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA)
Summary
Age-related macular degeneration (AMD) is one of the most common causes of visual impairment and sight loss in the elderly that may be irreversible. In the choroid and/or retina, where vessel leakage causes localized oedema and leads to damage to the retinal tissue. Treatment of this neovascular form of AMD (nvAMD), which is responsible for around 90% of acute blindness due to AMD [1], is primarily delivered through the application of inhibitors of vascular endothelial growth factor (VEGF) such as ranibizumab and aflibercept [2,3]. Anti-VEGF treatment efficacy is timedependent, and it correlates strongly with visual acuity at the time of the first injection [4,5]
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