Inherited mitochondrial dysfunction triggered by OPA1 mutation impacts the sensory innervation fibre identity- functionality and regenerative potential in the cornea

Authors
Meneux, Lna, Feret, Nadge, Pernot, Sarah, Girard, Mlissa, Sarkis, Solange, Caballero Megido, Alicia, Quiles, Melanie, Müller, Agns, Fichter, Laura, Vialaret, Jerome, Hirtz, Christophe, Delettre, Cecile, Michon, Frederic


Lab

Journal
Scientific Reports

Abstract
Mitochondrial dysfunctions are detrimental to organ metabolism. The cornea, transparent outmost layer of the eye, is prone to environmental aggressions, such as UV light, and therefore dependent on adequate mitochondrial function. While several reports have linked corneal defects to mitochondrial dysfunction, the impact of OPA1 mutation, known to induce such dysfunction, has never been studied in this context. We used the mouse line carrying OPA1delTTAG mutation to investigate its impact on corneal biology. To our surprise, neither the tear film composition nor the corneal epithelial transcriptomic signature were altered upon OPA1 mutation. However, when analyzing the corneal innervation, we discovered an undersensitivity of the cornea upon the mutation, but an increased innervation volume at 3 months. Furthermore, the fibre identity changed with a decrease of the SP+axons. Finally, we demonstrated that the innervation regeneration was less efficient and less functional in OPA1+/- corneas. Altogether, our study describes the resilience of the corneal epithelial biology, reflecting the mitohormesis induced by the OPA1 mutation, and the adaptation of the corneal innervation to maintain its functionality despite its morphogenesis defects. These findings will participate to a better understanding of the mitochondrial dysfunction on peripheral innervation.

Keywords/Topics
Mitochondria ;Cornea ;OPA1 Innervation ;Epithelium ;Tear film ;Transcriptomic; Proteomic; Subjects Eye abnormalities; Neurophysiology ;Peripheral neuropathies

BIOSEB Instruments Used:
Von Frey Filaments (BIO-VF-M)

Source :

https://www.nature.com/articles/s41598-024-68994-4

Produits associés

Filaments de Von Frey

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