Treatment of Inherited Eye Defects by Systemic Hematopoietic Stem Cell
Transplantation.
Authors Rocca CJ, Kreymerman A, Ur SN, Frizzi KE, Naphade S, Lau A, Tran T, Calcutt NA,
Goldberg JL, Cherqui S
Submitted By Nigel Calcutt on 11/18/2015
Status Published
Journal Investigative ophthalmology & visual science
Year 2015
Date Published 11/1/2015
Volume : Pages 56 : 7214 - 23
PubMed Reference 26540660
Abstract Cystinosis is caused by a deficiency in the lysosomal cystine transporter,
cystinosin (CTNS gene), resulting in cystine crystal accumulation in tissues. In
eyes, crystals accumulate in the cornea causing photophobia and eventually
blindness. Hematopoietic stem progenitor cells (HSPCs) rescue the kidney in a
mouse model of cystinosis. We investigated the potential for HSPC
transplantation to treat corneal defects in cystinosis., We isolated HSPCs from
transgenic DsRed mice and systemically transplanted irradiated Ctns-/- mice. A
year posttransplantation, we investigated the fate and function of HSPCs by in
vivo confocal and fluorescence microscopy (IVCM), quantitative RT-PCR (RT-qPCR),
mass spectrometry, histology, and by measuring the IOP. To determine the
mechanism by which HSPCs may rescue disease cells, we transplanted Ctns-/- mice
with Ctns-/- DsRed HSPCs virally transduced to express functional CTNS-eGFP
fusion protein., We found that a single systemic transplantation of wild-type
HSPCs prevented ocular pathology in the Ctns-/- mice. Engraftment-derived HSPCs
were detected within the cornea, and also in the sclera, ciliary body, retina,
choroid, and lens. Transplantation of HSPC led to substantial decreases in
corneal cystine crystals, restoration of normal corneal thickness, and lowered
IOP in mice with high levels of donor-derived cell engraftment. Finally, we
found that HSPC-derived progeny differentiated into macrophages, which displayed
tunneling nanotubes capable of transferring cystinosin-bearing lysosomes to
diseased cells., To our knowledge, this is the first demonstration that HSPCs
can rescue hereditary corneal defects, and supports a new potential therapeutic
strategy for treating ocular pathologies.

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