Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats

Andri K. Riau, Zhuojian Look, Gary H. F. Yam, Craig Boote, Qian Ma, Evelina J. Y. Han, Nur Zahirah binte M. Yusoff, Hon Shing Ong, Tze-Wei Goh, Nuur Shahinda Humaira binte Halim and Jodhbir S. Mehta ()
Additional contact information
Andri K. Riau: Singapore Eye Research Institute
Zhuojian Look: Singapore Eye Research Institute
Gary H. F. Yam: Singapore Eye Research Institute
Craig Boote: Cardiff University
Qian Ma: Cardiff University
Evelina J. Y. Han: Singapore Eye Research Institute
Nur Zahirah binte M. Yusoff: Singapore Eye Research Institute
Hon Shing Ong: Singapore Eye Research Institute
Tze-Wei Goh: Singapore Eye Research Institute
Nuur Shahinda Humaira binte Halim: Singapore Eye Research Institute
Jodhbir S. Mehta: Singapore Eye Research Institute

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea’s collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.

Date: 2024
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DOI: 10.1038/s41467-024-49008-3

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