Affordable Access

deepdyve-link
Publisher Website

Long-Term Effects of Gene Therapy in a Novel Mouse Model of Human MFRP-Associated Retinopathy.

Authors
  • Chekuri, Anil1
  • Sahu, Bhubanananda1, 2
  • Chavali, Venkata Ramana Murthy1, 3
  • Voronchikhina, Marina1
  • Soto-Hermida, Angel1
  • Suk, John J1
  • Alapati, Akhila N1
  • Bartsch, Dirk-Uwe1
  • Ayala-Ramirez, Raul4
  • Zenteno, Juan C4, 5
  • Dinculescu, Astra6
  • Jablonski, Monica M7
  • Borooah, Shyamanga1
  • Ayyagari, Radha1
  • 1 1 Shiley Eye Institute, University of California San Diego, La Jolla, California.
  • 2 2 Department of Ophthalmology and Visual sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky.
  • 3 3 Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
  • 4 4 Department of Genetics-Research Unit, Institute of Ophthalmology, Conde de Valenciana, Mexico City, Mexico. , (Mexico)
  • 5 5 Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, Mexico. , (Mexico)
  • 6 6 Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida.
  • 7 7 Department of Ophthalmology, The University of Tennessee Health Science Center, Hamilton Eye Institute, University of Tennessee, Memphis, Tennessee.
Type
Published Article
Journal
Human Gene Therapy
Publisher
Mary Ann Liebert
Publication Date
May 01, 2019
Volume
30
Issue
5
Pages
632–650
Identifiers
DOI: 10.1089/hum.2018.192
PMID: 30499344
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Patients harboring homozygous c.498_499insC mutations in MFRP demonstrate hyperopia, microphthalmia, retinitis pigmentosa, retinal pigment epithelial atrophy, variable degrees of foveal edema, and optic disc drusen. The disease phenotype is variable, however, with some patients maintaining good central vision and cone function till late in the disease. A knock-in mouse model with the c.498_499insC mutation in Mfrp (Mfrp KI/KI) was developed to understand the effects of these mutations in the retina. The model shares many of the features of human clinical disease, including reduced axial length, hyperopia, retinal degeneration, retinal pigment epithelial atrophy, and decreased electrophysiological responses. In addition, the eyes of these mice had a significantly greater refractive error (p < 0.01) when compared to age-matched wild-type control animals. Administration of recombinant adeno-associated virus-mediated Mfrp gene therapy significantly prevented thinning from retinal neurodegeneration (p < 0.005) and preserved retinal electrophysiology (p < 0.001) when treated eyes were compared to contralateral sham-treated control eyes. The Mfrp KI/KI mice will serve as a useful tool to model human disease and point to a potential gene therapeutic approach for patients with preserved vision and electrophysiological responses in MFRP-related retinopathy.

Report this publication

Statistics

Seen <100 times