June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Treatment of inherited eye defects by systemic hematopoietic stem cell transplantation
Author Affiliations & Notes
  • Jeffrey L Goldberg
    University of California, San Diego, La Jolla, CA
  • Celine Rocca
    University of California, San Diego, La Jolla, CA
  • Alex Kreymerman
    University of California, San Diego, La Jolla, CA
  • Stephanie Cherqui
    University of California, San Diego, La Jolla, CA
  • Footnotes
    Commercial Relationships Jeffrey Goldberg, None; Celine Rocca, None; Alex Kreymerman, None; Stephanie Cherqui, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3467. doi:
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      Jeffrey L Goldberg, Celine Rocca, Alex Kreymerman, Stephanie Cherqui; Treatment of inherited eye defects by systemic hematopoietic stem cell transplantation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3467.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Here we report that systemic transplantation of hematopoietic stem cells (HSCs) can treat corneal defects in a mouse model of a degenerative, hereditary metabolic disorder, cystinosis. Cystinosis is caused by deficiency of the lysosomal cystine transporter, cystinosin (Ctns), which leads to cystine and cystine crystal accumulation in most tissues. Kidney and eye are the primary affected organs. In eyes, cystine crystals accumulate in the cornea, as well as the iris, retina, and ocular muscles, leading to photophobia, iris crystals, synechiae, blepharospasm, retinal degeneration, and ultimately, if not treated, blindness.

Methods: To identify potential therapeutic strategies for treating cystinosis, we have been using the cystinosin ­knockout mouse (Ctns-/-), which develops human associated eye defects, to model cystinosis.

Results: After engrafting GFP-expressing HSCs into Ctns-/- mice, we detected a substantial number of bone marrow-derived cells (BMCs) within the cornea, sclera, ciliary body, retina and lens, demonstrating that normal, Ctns-expressing BMCs homed and migrated into diseased eyes. Strikingly, when examining eyes in Ctns-/- animals with high levels of engraftment, we detected a substantial decrease in corneal cystine crystals, particularly in the anterior cornea. We also found that the intraocular pressure and behavioral measures of vision were physiologically normal in the transplanted mice compared to the Ctns-/- controls. Finally, we observed that HSCs differentiated into phagocytic cells within the cornea and transferred cystinosin-bearing lysosomes via tunneling nanotubes (TNTs) to the adjacent host cells.

Conclusions: These data are consistent with a hypothesis that protein transfer from donor cells to host cells rescues the Ctns deficit and accounts for the dramatic impact of the HSCs on corneal preservation. Overall, this work is the first demonstration that HSCs can rescue corneal defects, which brings forth a new potential therapeutic strategy for treating ocular pathologies.


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