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

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 demons...

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Bibliographic Details
Published in:	Nature communications Vol. 15; no. 1; pp. 4959 - 17
Main Authors:	Riau, Andri K., Look, Zhuojian, Yam, Gary H. F., Boote, Craig, Ma, Qian, Han, Evelina J. Y., binte M. Yusoff, Nur Zahirah, Ong, Hon Shing, Goh, Tze-Wei, binte Halim, Nuur Shahinda Humaira, Mehta, Jodhbir S.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 11-06-2024 Nature Publishing Group Nature Portfolio
Subjects:	13/1 13/106 13/51 14/69 147/143 38/77 64/86 692/308/575 692/699/3161/3163 Acuity Animals Cell Differentiation Cell therapy Collagen Cornea Cornea - metabolism Cornea - pathology Corneal Keratocytes - metabolism Corneal Opacity - pathology Corneal Stroma - drug effects Corneal Stroma - metabolism Corneal Stroma - ultrastructure Differentiation Disease Models, Animal Fibroblasts Humanities and Social Sciences Humans Keratan sulfate Latency Male Males Microscopy Morphometry multidisciplinary Opacity Proteoglycans Rats Rats, Sprague-Dawley Recovery Recovery of Function Science Science (multidisciplinary) Therapy Transmission electron microscopy Visual Acuity Visual perception X-ray scattering
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Summary:	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. This study demonstrates the opacity resolution and visual function improvement following intrastromal injection of quiescent corneal stromal keratocytes but not stromal fibroblasts. The keratocyte therapy recapitulates native cornea’s collagen fibril organization and proteoglycans.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-49008-3