Mitofusin 2 (Mfn2) mediates the mitochondrial fusion in dynamic balance between mitochondrial fission and fusion. This study aimed to investigate the role of Mfn2 in mice corneal dysplasia with conditional knockout (CKO) technique. The Mfn2 CKO mice model was established with the Cre-loxP system. Each offspring of Le-Cre +/-; Mfn2 fl/fl (Mfn2 CKO) mice and Mfn2fl/fl (Mfn2 WT) mice was identified by polymerase chain reaction (PCR). Macroscopic observation, immunohistostaining and HE staining were used to evaluate the corneal morphologic development in Mfn2 CKO mice and Mfn2 WT mice. The cells proliferation and apoptosis were detected by BrdU labeling and TUNEL assay. Real-time PCR was used to detect mRNA expression of corneal markers (K12, Col1α1, Pax6, keratocan and NSE). Results showed that Mfn2 CKO mice showed increased corneal thickness, small eyeball from E15.5 to P60 and small eye crack after birth. The corneal stromal thickness significantly increased in Mfn2 CKO mice, and the random arrangement fibers of the corneal stroma increased in Mfn2 CKO mice. The proliferative cells in the cornea of Mfn2 CKO mice were less than in Mfn2 WT mice while the apoptotic cells in the cornea of Mfn2 CKO mice were increased. K12 and Pax6 expression decreased in the cornea and the Col1α1 expression increased in Mfn2 CKO mice as compared to Mfn2 WT mice. The expression of corneal stromal marker Col1α1 in the Mfn2 CKO mice was significantly higher than that in the Mfn2 WT mice. Corneal thickness was mainly caused by corneal stroma collagen proliferation. In conclusion, Mfn2 deletion affects corneal development, especially because of collagen hyperplasia in the corneal stroma.
Keywords: Mfn2; apoptosis; corneal development; mitochondria; proliferation.
Conflict of interest statement
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