Related Experiment Video

Updated: Jun 9, 2026

Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography
05:14

Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography

Published on: August 11, 2023

Broad spectrum antiangiogenic treatment for ocular neovascular diseases

Ofra Benny1, Kei Nakai, Takeru Yoshimura

  • 1Vascular Biology Program and Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America. ofra.bennyratsaby@childrens.harvard.edu

Plos One
|September 9, 2010
PubMed
Abstract

Insights

Lodamin, a novel broad-spectrum antiangiogenic drug, effectively reduced pathological neovascularization, leakage, and inflammation in an age-related macular degeneration (AMD) mouse model. This therapy shows promise for treating and preventing AMD by targeting key disease processes.

Area of Science:

  • Ophthalmology
  • Angiogenesis Research
  • Pharmacology

Background:

  • Pathological neovascularization, particularly choroidal neovascularization (CNV), drives wet age-related macular degeneration (AMD) and leads to vision loss.
  • Current treatments primarily inhibit vascular endothelial growth factor (VEGF), which may not address underlying causes and can have neuroprotective side effects.
  • A therapeutic strategy targeting neovascularization, leakage, and inflammation offers a potential shift in AMD treatment and prevention.

Purpose of the Study:

  • To evaluate the efficacy of a broad-spectrum antiangiogenic therapy in a mouse model of AMD.
  • To assess the drug's impact on key pathological processes including neovascularization, vascular leakage, and inflammation.
  • To determine the safety and potential for ophthalmic application of the therapeutic agent.

Main Methods:

  • Utilized a mouse model of AMD to test Lodamin, a polymeric formulation of TNP-470.
  • Assessed antiangiogenic, anti-leakage, and anti-inflammatory effects using various assays (Matrigel, DTH, Miles assay, laser-induced CNV, corneal micropocket).
  • Evaluated drug safety and toxicity through electroretinography (ERG) and histology.

Main Results:

  • Lodamin significantly reduced angiogenesis, vascular leakage, and inflammation in AMD models.
  • The drug suppressed pro-inflammatory cytokines, including monocyte chemotactic protein-1 (MCP-1/Ccl2), in CNV lesions.
  • Lodamin demonstrated the ability to regress established CNV lesions and showed minimal toxicity in mice.

Conclusions:

  • Lodamin, a first-in-class broad-spectrum antiangiogenic drug, is effective for treating corneal and retinal neovascularization.
  • Its properties make it particularly suitable for ophthalmic applications.
  • Broad-spectrum antiangiogenic drugs represent a promising therapeutic approach for AMD treatment and prevention.

Related Concept Videos

Open Angle Glaucoma: Treatment01:27

Open Angle Glaucoma: Treatment

In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
Drugs such as carbonic anhydrase inhibitors, α2- and...
Angle Closure Glaucoma: Treatment01:28

Angle Closure Glaucoma: Treatment

Angle-closure glaucoma, or closed-angle glaucoma, is an eye condition where the iris bulges out and blocks the iridocorneal angle, resulting in a buildup of aqueous humor and increased intraocular pressure. Immediate medical attention is necessary due to the sudden onset of symptoms. The treatment for angle-closure glaucoma includes short-term and long-term approaches. Short-term treatment involves using eye drops like pilocarpine to lower intraocular pressure by increasing aqueous humor...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Diabetic Retinopathy01:27

Diabetic Retinopathy

DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...