Gene Therapy Restores Mfrp and Corrects Axial Eye Length

Gabriel Velez; Stephen H Tsang; Yi-Ting Tsai; Chun-Wei Hsu; Anuradha Gore; Aliaa H Abdelhakim; MaryAnn Mahajan; Ronald H Silverman; Janet R Sparrow; Alexander G Bassuk; Vinit B Mahajan

doi:10.1038/s41598-017-16275-8

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Gene Therapy Restores Mfrp and Corrects Axial Eye Length

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Gene Therapy Restores Mfrp and Corrects Axial Eye Length

Gabriel Velez, Stephen H Tsang, Yi-Ting Tsai, Chun-Wei Hsu, Anuradha Gore, Aliaa H Abdelhakim, MaryAnn Mahajan, Ronald H Silverman, Janet R Sparrow, Alexander G Bassuk, …

Scientific reports, Vol.7(1), pp.16151-8

11/23/2017

DOI: 10.1038/s41598-017-16275-8

PMCID: PMC5701072

PMID: 29170418

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Abstract

Hyperopia (farsightedness) is a common and significant cause of visual impairment, and extreme hyperopia (nanophthalmos) is a consequence of loss-of-function MFRP mutations. MFRP deficiency causes abnormal eye growth along the visual axis and significant visual comorbidities, such as angle closure glaucoma, cystic macular edema, and exudative retinal detachment. The Mfrp /Mfrp mouse is used as a pre-clinical animal model of retinal degeneration, and we found it was also hyperopic. To test the effect of restoring Mfrp expression, we delivered a wild-type Mfrp to the retinal pigmented epithelium (RPE) of Mfrp /Mfrp mice via adeno-associated viral (AAV) gene therapy. Phenotypic rescue was evaluated using non-invasive, human clinical testing, including fundus auto-fluorescence, optical coherence tomography, electroretinography, and ultrasound. These analyses showed gene therapy restored retinal function and normalized axial length. Proteomic analysis of RPE tissue revealed rescue of specific proteins associated with eye growth and normal retinal and RPE function. The favorable response to gene therapy in Mfrp /Mfrp mice suggests hyperopia and associated refractive errors may be amenable to AAV gene therapy.

Details

Title: Subtitle: Gene Therapy Restores Mfrp and Corrects Axial Eye Length
Creators: Gabriel Velez - Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA
Stephen H Tsang - Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, USA. sht2@columbia.edu
Yi-Ting Tsai - Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, USA
Chun-Wei Hsu - Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, USA
Anuradha Gore - Omics Laboratory, Stanford University, Palo Alto, CA, USA
Aliaa H Abdelhakim - Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, USA
MaryAnn Mahajan - Omics Laboratory, Stanford University, Palo Alto, CA, USA
Ronald H Silverman - Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, USA
Janet R Sparrow - Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, USA
Alexander G Bassuk - Palo Alto Veterans Administration, Palo Alto, CA, USA. alexander-bassuk@uiowa.edu
Vinit B Mahajan - Palo Alto Veterans Administration, Palo Alto, CA, USA. vinit.mahajan@stanford.edu
Resource Type: Journal article
Publication Details: Scientific reports, Vol.7(1), pp.16151-8
DOI: 10.1038/s41598-017-16275-8
PMID: 29170418
PMCID: PMC5701072
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 EY025225 / NEI NIH HHS P30 EY026877 / NEI NIH HHS R01 EY018213 / NEI NIH HHS P30 CA013696 / NCI NIH HHS R01 EY024698 / NEI NIH HHS T32 GM007337 / NIGMS NIH HHS R01 EY026682 / NEI NIH HHS R01 EY024665 / NEI NIH HHS R21 AG050437 / NIA NIH HHS P30 EY019007 / NEI NIH HHS
Language: English
Date published: 11/23/2017
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984070766302771

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