AAV2/9-mediated gene transfer into murine lacrimal gland leads to a long-term targeted tear film modification

Gautier, Benoît; Meneux, Lena; Feret, Nadege; Audrain, Christine; Hudecek, Laetitia; Kuony, Alison; Bourdon, Aurélien; Guiner, Caroline Le; Blouin, Véronique; Delettre, Cécile; Michon, Frédéric

doi:10.1016/j.omtm.2022.08.006

Cited by 2 publications

(2 citation statements)

References 60 publications

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“…Sensitivity was measured using Von Frey filaments (Bioseb, France, reference bio-VF-M) as previously described 65 . Filament generate a force between 0.008 and 0.6g when pressed against the centre of the cornea of an immobilized mouse.…”

Section: Methodsmentioning

confidence: 99%

“…The image acquisition was performed as previously described. 65 Whole-cornea images were acquired on a Leica Thunder Imager Tissue microscope using the navigator module with the large volume computational clearing (LVCC) process. Images were obtained with LAS X software (3.7.4) using a 20X/0.55 objective and processed with Imaris Bitplane software (version 9.8.0).…”

Section: Imaging and Processingmentioning

confidence: 99%

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

Meneux,

Feret,

Pernot

et al. 2024

Preprint

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Imaging and Processingmentioning

confidence: 99%

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

Meneux,

Feret,

Pernot

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

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

Meneux,

Feret,

Pernot

et al. 2024

Sci Rep

View full text Add to dashboard Cite

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 OPA1 delTTAG 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.

show abstract

AAV2/9-mediated gene transfer into murine lacrimal gland leads to a long-term targeted tear film modification

Cited by 2 publications

References 60 publications

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

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

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

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