Safety and Feasibility of Intrastromal Injection of Cultivated Human Corneal Stromal Keratocytes as Cell-Based Therapy for Corneal Opacities

Investigative Ophthalmology & Visual Science
Gary Hin-Fai YamJodhbir S Mehta

Abstract

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. 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 × 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. 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 a...Continue Reading

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Citations

Oct 26, 2018·Stem Cell Research & Therapy·Koushik ChakrabartyArkasubhra Ghosh
Sep 25, 2020·Science Translational Medicine·Yonglong GuoJiansu Chen
Jan 5, 2020·Stem Cell Research & Therapy·Francisco BandeiraJodhbir S Mehta
Aug 9, 2020·Stem Cells International·Jasmin S NurkovićZana Dolićanin
Jun 13, 2020·Nature Reviews. Disease Primers·Yu Qiang SohJodhbir S Mehta
Dec 21, 2020·Journal of Cellular and Molecular Medicine·Shenyang LiJiansu Chen
Sep 27, 2020·Experimental Eye Research·Irona KhandakerGary Hin-Fai Yam
May 23, 2020·Experimental Eye Research·Gary H F YamVishal Jhanji
Jun 18, 2021·World Journal of Stem Cells·Giovanni MiottiMarco Zeppieri
Sep 7, 2021·Journal of Cellular and Molecular Medicine·Nina SeidelmannMatthias Fuest

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