PMID- 27100624
OWN - NLM
STAT- MEDLINE
DCOM- 20160902
LR  - 20220409
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 4
DP  - 2016
TI  - Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular 
      Epithelium in a Rabbit Model of Dry-Eye Syndrome.
PG  - e0153573
LID - 10.1371/journal.pone.0153573 [doi]
LID - e0153573
AB  - Application of autologous serum eye drops (SEDs) is a recognized means to treat 
      severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of 
      preparing SEDs from some patients, producing SEDs from allogeneic blood donations 
      is gaining popularity. A major safety concern associated with allogeneic blood is 
      virus transmission. We therefore herein evaluated the possibility of applying a 
      solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts 
      of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from 
      the blood of five rabbits were pooled and divided into two sub-pools. One was 
      untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl 
      phosphate/1% Triton X-45 at 31 degrees C for 1 h (S/D-SEDs). DES was induced in rabbits 
      using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of 
      two rabbits each. One group was untreated (control), three were treated twice 
      daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an 
      additional 0.1% BAC (as the negative control). The DES condition was determined 
      by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein 
      staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal 
      inflammatory marker (tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-8, and 
      IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein 
      profiles and transforming growth factor (TGF)-beta contents. Animal experiments 
      showed that tear secretion did not significantly differ between the SED and 
      S/D-SED groups but was significantly higher than in the PBS group. Eye 
      fluorescein staining revealed dramatic improvements in epithelial defects in 
      groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed 
      microscopic epithelial layers similar to those of the untreated controls. 
      Inflammatory markers and TUNEL studies showed that healthy epithelium had been 
      restored in groups treated with SEDs or S/D-SEDs. In conclusion, this preclinical 
      study supports the possibility of using S/D virally inactivated SEDs to treat DES 
      and restore a normal epithelium.
FAU - Tseng, Ching-Li
AU  - Tseng CL
AD  - Graduate Institute of Biomedical Materials and Tissue Engineering, College of 
      Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
FAU - Chen, Zhi-Yu
AU  - Chen ZY
AD  - Graduate Institute of Biomedical Materials and Tissue Engineering, College of 
      Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
FAU - Renn, Ting-Yi
AU  - Renn TY
AD  - Graduate Institute of Biomedical Materials and Tissue Engineering, College of 
      Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
FAU - Hsiao, Shun-Hung
AU  - Hsiao SH
AD  - Graduate Institute of Biomedical Materials and Tissue Engineering, College of 
      Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
FAU - Burnouf, Thierry
AU  - Burnouf T
AD  - Graduate Institute of Biomedical Materials and Tissue Engineering, College of 
      Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160421
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Detergents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Solvents)
SB  - IM
MH  - Animals
MH  - Cornea/*cytology
MH  - Cytokines/metabolism
MH  - Detergents/*pharmacology
MH  - Disinfection
MH  - Dry Eye Syndromes/chemically induced/pathology/*prevention & control
MH  - Epithelium/*growth & development
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Ophthalmic Solutions/*administration & dosage
MH  - Rabbits
MH  - Serum/*chemistry/virology
MH  - Solvents/*pharmacology
MH  - *Virus Inactivation
PMC - PMC4839776
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/04/23 06:00
MHDA- 2016/09/03 06:00
PMCR- 2016/04/21
CRDT- 2016/04/22 06:00
PHST- 2015/12/24 00:00 [received]
PHST- 2016/03/31 00:00 [accepted]
PHST- 2016/04/22 06:00 [entrez]
PHST- 2016/04/23 06:00 [pubmed]
PHST- 2016/09/03 06:00 [medline]
PHST- 2016/04/21 00:00 [pmc-release]
AID - PONE-D-15-55825 [pii]
AID - 10.1371/journal.pone.0153573 [doi]
PST - epublish
SO  - PLoS One. 2016 Apr 21;11(4):e0153573. doi: 10.1371/journal.pone.0153573. 
      eCollection 2016.