PMID- 30025076
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20190318
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 59
IP  - 8
DP  - 2018 Jul 2
TI  - Safety and Feasibility of Intrastromal Injection of Cultivated Human Corneal
      Stromal Keratocytes as Cell-Based Therapy for Corneal Opacities.
PG  - 3340-3354
LID - 10.1167/iovs.17-23575 [doi]
AB  - Purpose: To evaluate the safety and feasibility of intrastromal injection of
      human corneal stromal keratocytes (CSKs) and its therapeutic effect on a rodent
      early corneal opacity model. Methods: Twelve research-grade donor corneas were
      used in primary culture to generate quiescent CSKs and activated stromal
      fibroblasts (SFs). Single and repeated intrastromal injections of 2 to 4 x 104
      cells to rat normal corneas (n = 52) or corneas with early opacities induced by
      irregular phototherapeutic keratectomy (n = 16) were performed, followed by
      weekly examination of corneal response under slit-lamp biomicroscopy and in vivo 
      confocal microscopy with evaluation of haze level and stromal reflectivity, and
      corneal thickness using anterior segment optical coherence tomography (AS-OCT).
      Time-lapse tracing of Molday ION-labelled cells was conducted using Spectralis
      OCT and label intensity was measured. Corneas were collected at time intervals
      for marker expression by immunofluorescence, cell viability, and apoptosis
      assays. Results: Injected CSKs showed proper marker expression with negligible
      SF-related features and inflammation, hence maintaining corneal clarity and
      stability. The time-dependent loss of injected cells was recovered by repeated
      injection, achieving an extended expression of human proteoglycans inside rat
      stroma. In the early corneal opacity model, intrastromal CSK injection reduced
      stromal reflectivity and thickness, resulting in recovery of corneal clarity,
      whereas noninjected corneas were thicker and had haze progression. Conclusions:
      We demonstrated the safety, feasibility, and therapeutic efficacy of intrastromal
      CSK injection. The cultivated CSKs can be a reliable cell source for potential
      cell-based therapy for corneal opacities.
FAU - Yam, Gary Hin-Fai
AU  - Yam GH
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
AD  - Eye-Academic Clinical Program, Duke-National University Singapore Graduate
      Medical School, Singapore.
FAU - Fuest, Matthias
AU  - Fuest M
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
AD  - Department of Ophthalmology, Rheinisch-Westfalische Technische Hochschule (RWTH) 
      Aachen University, Aachen, Germany.
FAU - Yusoff, Nur Zahirah Binte M
AU  - Yusoff NZBM
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Goh, Tze-Wei
AU  - Goh TW
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Bandeira, Francisco
AU  - Bandeira F
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Setiawan, Melina
AU  - Setiawan M
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Seah, Xin-Yi
AU  - Seah XY
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Lwin, Nyein-Chan
AU  - Lwin NC
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Stanzel, Tisha P
AU  - Stanzel TP
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
FAU - Ong, Hon-Shing
AU  - Ong HS
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
AD  - Singapore National Eye Centre, Singapore.
FAU - Mehta, Jodhbir S
AU  - Mehta JS
AD  - Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute,
      Singapore.
AD  - Eye-Academic Clinical Program, Duke-National University Singapore Graduate
      Medical School, Singapore.
AD  - Singapore National Eye Centre, Singapore.
AD  - School of Material Science and Engineering, Nanyang Technological University,
      Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers/metabolism
MH  - Cell Survival
MH  - Cell- and Tissue-Based Therapy/*methods
MH  - Cells, Cultured
MH  - Corneal Keratocytes/cytology/metabolism/*physiology
MH  - Corneal Opacity/metabolism/*therapy
MH  - *Corneal Stroma
MH  - *Disease Models, Animal
MH  - Feasibility Studies
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Injections, Intraocular
MH  - Male
MH  - Microscopy, Confocal
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Slit Lamp Microscopy
MH  - Tomography, Optical Coherence
EDAT- 2018/07/20 06:00
MHDA- 2019/03/19 06:00
CRDT- 2018/07/20 06:00
PHST- 2018/07/20 06:00 [entrez]
PHST- 2018/07/20 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
AID - 2687658 [pii]
AID - 10.1167/iovs.17-23575 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2018 Jul 2;59(8):3340-3354. doi:
      10.1167/iovs.17-23575.