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Methods and Compounds for Promoting Vessel Regression

a technology of regression and hvs, applied in the field of methods and compounds for promoting vessel regression, can solve the problems of permanent blindness if left untreated, degeneration of hvs, etc., and achieve the effect of improving the parameter

Inactive Publication Date: 2012-07-19
MASSACHUSETTS EYE & EAR INFARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0022]In some embodiments, the method further includes administering the candidate therapeutic compound to an animal model of a disorder associated with neovascularization, and monitoring the animal model for an effect of the candidate therapeutic compound on a parameter of the disorder, e.g., vascularisation, in the animal. A candidate therapeutic compound that causes an improvement in the parameter in the animal model is a candidate therapeutic agent for the treatment of the disorder. In some embodiments, the methods further include administ

Problems solved by technology

In humans, failure of the hyaloid vascular system to regress can lead to a condition known as persistent hyperplastic primary vitreous (PHPV), which can result in permanent blindness if left untreated.
220 (6):257-63 (1983)) and competition between the blood vessels in the retina and the lens for the blood flow can lead to the degeneration of the HVS when the retinal blood vessels become larger and require more nutrients.

Method used

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  • Methods and Compounds for Promoting Vessel Regression
  • Methods and Compounds for Promoting Vessel Regression
  • Methods and Compounds for Promoting Vessel Regression

Examples

Experimental program
Comparison scheme
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example 1

Observation of Whole-Mount Specimens

[0095]To document the changes in the hyaloid vascular system associated with development in the cornea, whole-mount specimens were observed.

[0096]A total of 44 C57BL / 6 newborn male and female litters were obtained from Jackson Laboratories (Bar Harbor, Me.) were used for the experiments described herein. The age of the newborn mice was expressed in terms of post-gestational days. The newborn mice were sacrificed on post-gestational days 1, 4, 8, 16, 24, and 30 (i.e., P1, p4, p16, p24, and P30). Four eyes per each post-gestational day were used for the histological study. For the lens and vitreous protein extraction were used 20 eyes of P 1 mice, 20 eyes of P 4 mice, 12 eyes of P 8 mice and 12 eyes of P 16 mice. Each of the 12 newborn mice used for the histological study was perfused with 4% paraformaldehyde in PBS under general anesthesia administered by intramuscular injection of a mixture of ketamine (200 mg / kg) and xylazine (10 mg / kg). The eyes...

example 2

Differential Expression of Activin Receptor-Like Kinase 1 (ALK1)

[0138]The activin receptor-like kinase 1 (ALK1), a TGF-beta1 type I receptor, plays an inhibitory role in angiogenesis and vascular development. Mutations of ALK1 gene are linked to human type II hereditary hemorrhagic telangiectasia. Our purpose was to develop a mouse model to study the differential expression of proteins during the phase of Hyaloid Vascular System (HVS) regression and determine the role of ALK1 in this model.

[0139]Materials and Methods: Thirty-two newborn C57BL / 6 mice were sacrificed on post-gestational days 1 (n=20 eyes), 4 (n=20 eyes), 8 (n=12 eyes), and 16 (n=12 eyes). The lens, the Pupillary Membrane (PM), the Tunica Vasculosa Lentis (TVL) and the primary vitreous containing the Vasa Hyaloidea Propria (VHP) were isolated. Proteins were extracted from each specimen, loaded onto nonlinear immobilized pH gradient (IPG) gel strips, and separated by isoelectric points and molecular weights. Protein exp...

example 3

Progressive Regression of HVS in the Mouse and the Differential Protein Expression Profile

[0143]A time course experiment was designed to examine the changes in protein expression at P1 and P16 throughout the HVS regression process. As this is the first reported application of proteomic analysis on HVS regression, several conditions for tissue selection and preparation were developed and optimized to obtain clean specimens of the lens and vitreous for 2-DE gels.

[0144]Mouse Anterior Tissue Preparation for 2-DE Gels

[0145]For the protein extraction and ALK1 immunolocalization studies, newborn mice were sacrificed on post-natal days 1, 4 and 16. Using a dry ice bed, frozen mouse eyes were scraped with a blade (Beaver #15) to remove the cornea, conjunctiva, sclera, ciliary body, uvea, and retina, leaving the lens surrounded by the PM, TVL, and primary vitreous (containing VHP). The dry ice bed was used to prevent warming of the specimen, tissue melting, and subsequent protein denaturation...

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Abstract

The present invention relates, at least in part, to methods and compositions for treating and diagnosing disorders associated with neovascularization, and methods for identifying targets and compositions used in treating and diagnosing such disorders.

Description

CLAIM OF PRIORITY[0001]This application is a continuation of U.S. application Ser. No. 13 / 007,202, which was filed on Jan. 14, 2011, which is a continuation of U.S. application Ser. No. 11 / 363,402, which was filed on Feb. 24, 2006, which claims the benefit under 35 USC §119(e) of U.S. Provisional Patent Application Ser. Nos. 60 / 656,168, filed on Feb. 24, 2005, and 60 / 719,998, filed on Sep. 23, 2005. The entire contents of each of these applications is hereby incorporated by reference.TECHNICAL FIELD[0002]This invention relates to methods and compounds for promoting vessel regression, e.g., to treat disorders associated with neovascularization.BACKGROUND[0003]The hyaloid vascular system (HVS) is a transiently existing network of capillaries that function to nourish the immature lens and primary vitreous of the developing eye. The hyaloid artery (HA) runs from the back of the eye to the embryonic lens giving rise to a capillary plexus that surrounds the lens, consisting of the vasa hy...

Claims

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Application Information

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IPC IPC(8): A61K38/45A61P35/00C12Q1/48A61P27/06A61K48/00A61P27/02A61P37/06
CPCC12Q1/485G01N33/566G01N33/573G01N2800/32G01N2800/16G01N2800/164G01N33/6893A61P27/02A61P27/06A61P35/00A61P37/06A61P9/00
Inventor AZAR, DIMITRI T.ALBÉ, ELENACHANG, JIN-HONG
Owner MASSACHUSETTS EYE & EAR INFARY