Convergence of human genetics and animal studies: Gene therapy for X-linked retinoschisis

Ronald A. Bush, Lisa L. Wei, Paul A. Sieving

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. Xlinked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS.

Original languageEnglish (US)
Article numbera017368
Pages (from-to)1-13
Number of pages13
JournalCold Spring Harbor Perspectives in Medicine
Issue number8
StatePublished - Aug 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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