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

角膜细胞分化对雄性大鼠角膜混浊消退及视功能恢复的影响

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作者: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, Jodhbir S Mehta

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.

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