scholarly journals Sustained-Release Microspheres of Rivoceranib for the Treatment of Subfoveal Choroidal Neovascularization

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1548
Author(s):  
E Seul Kim ◽  
Min Sang Lee ◽  
Hayoung Jeong ◽  
Su Yeon Lim ◽  
Doha Kim ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Therapeutic Potential ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Vegf Receptor ◽  
Sustained Drug Release ◽  
Age Related ◽  
Subfoveal Choroidal Neovascularization ◽  
Endothelial Growth Factor

The wet type of age-related macular degeneration (AMD) accompanies the subfoveal choroidal neovascularization (CNV) caused by the abnormal extension or remodeling of blood vessels to the macula and retinal pigment epithelium (RPE). Vascular endothelial growth factor (VEGF) is known to play a crucial role in the pathogenesis of the disease. In this study, we tried to repurpose an investigational anticancer drug, rivoceranib, which is a selective inhibitor of VEGF receptor-2 (VEGFR2), and evaluate the therapeutic potential of the drug for the treatment of wet-type AMD in a laser-induced CNV mouse model using microsphere-based sustained drug release formulations. The PLGA-based rivoceranib microsphere can carry out a sustained delivery of rivoceranib for 50 days. When administered intravitreally, the sustained microsphere formulation of rivoceranib effectively inhibited the formation of subfoveal neovascular lesions in mice.

scholarly journals Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ling Luo ◽  
Hironori Uehara ◽  
Xiaohui Zhang ◽  
Subrata K Das ◽  
Thomas Olsen ◽  
...  
Keyword(s):  
Vascular Invasion ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Vegf Receptor ◽  
Photoreceptor Layer ◽  
Age Related ◽  
Gene Ablation ◽  
Transgenic Murine Models ◽  
Endothelial Growth Factor

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life.

scholarly journals Pharmaceutical Induction of PGC-1α Promotes Retinal Pigment Epithelial Cell Metabolism and Protects against Oxidative Damage

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sangeeta Satish ◽  
Hannah Philipose ◽  
Mariana Aparecida Brunini Rosales ◽  
Magali Saint-Geniez
Keyword(s):  
Cell Death ◽  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Therapeutic Potential ◽  
Retinal Pigment Epithelial Cell ◽  
Cell Metabolism ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related

Retinal pigment epithelium (RPE) dysfunction due to accumulation of reactive oxygen species and oxidative damage is a key event in the development of age-related macular degeneration (AMD). Here, we examine the therapeutic potential of ZLN005, a selective PGC-1α transcriptional regulator, in protecting RPE from cytotoxic oxidative damage. Gene expression analysis on ARPE-19 cells treated with ZLN005 shows robust upregulation of PGC-1α and its associated transcription factors, antioxidant enzymes, and mitochondrial genes. Energetic profiling shows that ZLN005 treatment enhances RPE mitochondrial function by increasing basal and maximal respiration rates, and spare respiratory capacity. In addition, ZLN005 robustly protects ARPE-19 cells from cell death caused by H2O2, ox-LDL, and NaIO3 without exhibiting any cytotoxicity under basal conditions. ZLN005 protection against H2O2-mediated cell death was lost in PGC-1α-silenced cells. Our data indicates that ZLN005 efficiently protects RPE cells from oxidative damage through selective induction of PGC-1α and its target antioxidant enzymes. ZLN005 may serve as a novel therapeutic agent for retinal diseases associated with RPE dystrophies.

scholarly journals Potential Treatment of Retinal Diseases with Iron Chelators

2018 ◽  
Vol 11 (4) ◽  
pp. 112 ◽  
Author(s):  
Wanting Shu ◽  
Joshua Dunaief
Keyword(s):  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Hereditary Diseases ◽  
Iron Chelators ◽  
Excess Iron ◽  
Age Related

Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation. In addition to hereditary causes, dietary or parenteral iron supplementation has been recently reported to elevate iron levels in the retinal pigment epithelium (RPE) and promote retinal degeneration. Ocular siderosis from intraocular foreign bodies or subretinal hemorrhage can also lead to retinopathy. Evidence from mice and humans suggests that iron toxicity may contribute to age-related macular degeneration pathogenesis. Iron chelators can protect photoreceptors and RPE in various mouse models. The therapeutic potential for iron chelators is under investigation.

The Effects of Indocyanine Green Dye-Enhanced Photocoagulation on the Blood Flow in the Choriocapillaris and the Choroidal Neovascularization (CNV)

2000 ◽  
Author(s):  
C. von Kerczek ◽  
L. Zhu ◽  
A. Ernest ◽  
C. Eggleton ◽  
L. D. T. Topoleski ◽  
...  
Keyword(s):  
Laser Treatment ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The United States ◽  
Age Related Macular Degeneration ◽  
Central Vision ◽  
Age Related ◽  
Direct Laser

Abstract Age-related macular degeneration (AMD) is the most common cause of vision loss in patients aged 65 years and older in the United States. In the majority of cases, the loss of central vision is secondary to exudative changes and fibrovascular scarring following choroidal neovascularization (CNV). Prompt laser treatment is recommended [Asrani et al., 1996; Macular Photocoagulation Study Group, 1993; Schneider et al, 1998]. However, direct laser treatment to the entire subfoveal lesion is almost invariably associated with immediate loss of central vision. Loss of central vision may be due to direct damage to foveal photoreceptors and retinal pigment epithelium or from damage to the nerve fiber layer serving foveal function [Han et al., 1988].

Pattern Dystrophies and Choroidal Neovascularization

2017 ◽  
pp. 313-320
Keyword(s):  
Visual Acuity ◽  
Choroidal Neovascularization ◽  
Middle Ages ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
Pattern Dystrophy ◽  
Good Visual Acuity ◽  
Age Related

Pattern dystrophies are hereditary dystrophies that come from retinal pigment epithelium and located in the macula. The diagnosis is usually made around the middle ages. Pigment accumulations in the macula and around the macula, are seen bilaterally and symmetrical in the beginning, are sub-divided depending on pigment scattering pattern. These are adult-onset foveomacular vitelliform dystrophy, butterfly-like pattern dystrophy, reticular pattern dystrophy, and fundus pulverulentus. Usually in patients with pattern dystrophy have good visual acuity, after progression central visual acuity lessens with RPE atrophy or choroidal neovascularization development. In choroidal neovascularization secondary to age-related macular degeneration there is no typical pigmentation in the macula. On the other hand, in choroidal neovascularization related to pattern dystrophy, hemorrhage, and intra/subretinal fluid do not exist. Today choroidal neovascularization prognosis, which is treated with intravitreal anti-VEGF injections, is quite good. At least, one eye of the patients has satisfactory vision. Sometimes, in especially patients with isolated pattern dystrophy, not hereditary, there may be spontaneous regression of choroidal neovascularization.

New Vessel Formation, Choroidal Neovascularization, and Causes

2017 ◽  
pp. 273-279
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Blood Vessels ◽  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Vessel Formation ◽  
Age Related

Choroidal neovascularization is defined as the formation of new blood vessels located between the retinal pigment epithelium and the Bruch's membrane. The neovascular structure is taken origin from the choroid, crosses the Bruch membrane, and affects the photoreceptors with RPE. It is most frequently observed in Age-Related Macular Degeneration and less frequently in other eye diseases. This review mentions choroidal neovascularization and its causes as a general.

Sign in / Sign up

Export Citation Format

Share Document