Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina

Tao Wang, Gary Steel, Ann H. Milam, David Valle

Research output: Contribution to journalArticle

Abstract

Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina (GA), an autosomal recessive disorder characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat(-/-)) produced by gene targeting. We evaluated the mice over a 12-month period by measurement of plasma amino acids, electroretinograms, and retinal histologic and ultrastructural studies. We found that an arginine-restricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in Oat(-/-). This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA.

Original languageEnglish (US)
Pages (from-to)1224-1229
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2000

Fingerprint

Gyrate Atrophy
Retinal Degeneration
Ornithine
Arginine
Ornithine-Oxo-Acid Transaminase
Diet
Gene Targeting
Retina
Amino Acids

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{c381161744eb4046a241942506851643,
title = "Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina",
abstract = "Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina (GA), an autosomal recessive disorder characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat(-/-)) produced by gene targeting. We evaluated the mice over a 12-month period by measurement of plasma amino acids, electroretinograms, and retinal histologic and ultrastructural studies. We found that an arginine-restricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in Oat(-/-). This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA.",
author = "Tao Wang and Gary Steel and Milam, {Ann H.} and David Valle",
year = "2000",
month = "2",
day = "1",
doi = "10.1073/pnas.97.3.1224",
language = "English (US)",
volume = "97",
pages = "1224--1229",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "3",

}

TY - JOUR

T1 - Correction of ornithine accumulation prevents retinal degeneration in a mouse model of gyrate atrophy of the choroid and retina

AU - Wang, Tao

AU - Steel, Gary

AU - Milam, Ann H.

AU - Valle, David

PY - 2000/2/1

Y1 - 2000/2/1

N2 - Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina (GA), an autosomal recessive disorder characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat(-/-)) produced by gene targeting. We evaluated the mice over a 12-month period by measurement of plasma amino acids, electroretinograms, and retinal histologic and ultrastructural studies. We found that an arginine-restricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in Oat(-/-). This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA.

AB - Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy of the choroid and retina (GA), an autosomal recessive disorder characterized by ornithine accumulation and a progressive chorioretinal degeneration of unknown pathogenesis. To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat(-/-)) produced by gene targeting. We evaluated the mice over a 12-month period by measurement of plasma amino acids, electroretinograms, and retinal histologic and ultrastructural studies. We found that an arginine-restricted diet substantially reduces plasma ornithine levels and completely prevents retinal degeneration in Oat(-/-). This result indicates that ornithine accumulation is a necessary factor in the pathophysiology of the retinal degeneration in GA and that restoration of OAT activity in retina is not required for effective treatment of GA.

UR - http://www.scopus.com/inward/record.url?scp=0033950654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033950654&partnerID=8YFLogxK

U2 - 10.1073/pnas.97.3.1224

DO - 10.1073/pnas.97.3.1224

M3 - Article

C2 - 10655512

AN - SCOPUS:0033950654

VL - 97

SP - 1224

EP - 1229

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 3

ER -