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Ocular instillation of vitamin A–coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD

Ocular instillation of vitamin A–coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD

Authors :
Ohigashi, Hiroyuki
Hashimoto, Daigo
Hayase, Eiko
Takahashi, Shuichiro
Ara, Takahide
Yamakawa, Tomohiro
Sugita, Junichi
Onozawa, Masahiro
Nakagawa, Masao
Teshima, Takanori
Source :
Blood Advances; April 2019, Vol. 3 Issue: 7 p1003-1010, 8p
Publication Year :
2019

Abstract

Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A–coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.

Details

Language :
English
ISSN :
24739529 and 24739537
Volume :
3
Issue :
7
Database :
Supplemental Index
Journal :
Blood Advances
Publication Type :
Periodical
Accession number :
ejs53091737
Full Text :
https://doi.org/10.1182/bloodadvances.2018028431