Hermawan, Dicky and Komaratih, Evelyn and Sudiana, I. Ketut (2026) Delayed limbal mesenchymal stem cell secretome therapy attenuates NF-κB, IL-8, and MMP-9 expression following phacoemulsification-induced corneal endothelial damage. BMC Ophthalmology, 26 (1).

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Abstract

Background: The limbal mesenchymal stem cell secretome (LMSC-S) contains anti-inflammatory cytokines that suppress extracellular matrix (ECM) degradation in phacoemulsification-damaged corneal endothelial cells. This study aimed to evaluate the effect of LMSC-S on post- phacoemulsification ECM degradation. Methods: Thirty-six eyes from 32 New Zealand white rabbits (Oryctolagus cuniculus) were included. The normal group (N) comprised neither exposed nor treated eyes. Control group 1 (C1) served as the control for treatment group 1 (T1), where LMSC-S was administered simultaneously with phacoemulsification. Control group 2 (C2) served as the control for treatment group 2 (T2), which underwent LMSC-S administration 3 days after phacoemulsification. In this study, exposure to ultrasound from a phacoemulsification machine damaged corneal endothelial cells. Nuclear factor kappa-B (NF-κB), interleukin-8 (IL-8), and matrix metalloproteinase-9 (MMP-9) expression in macrophages was measured by immunohistochemistry (IHC) and IL-8 level in the aqueous humor was measured by enzyme-linked immunosorbent assay. Results: The comparison of NF-κB macrophage expression between groups C2-T2 (p < 0.001); IL-8 macrophage between groups C1-T1 (p = 0.04) and C2-T2 (p = 0.002); MMP-9 macrophage between groups C1-T1 (p = 0.03) and C2-T2 (p = 0.002) showed a significant difference. NF-κB, IL-8, and MMP-9 macrophage expression level in the T2 group was closest to that in the N group. MMP-9 macrophage expression following LMSC-S administration on the third day post-phacoemulsification correlated strongly and positively with IL-8 macrophage expression (β = 0.861; p < 0.001), NF-κB macrophage expression (β = 0.896; p < 0.001), and LMSC-S administration (β = -0.978; p < 0.001). Conclusion: In this experimental animal model, LMSC-S administration three days post-phacoemulsification reduced MMP-9 expression more effectively than simultaneous administration. However, the therapeutic potential of LMSC-Ss requires further human validation. © The Author(s) 2026.

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