Biology subjects

Meneux, L.

Publications and source records attributed to Meneux, L..

3 recordsLinked to original sources

bioRxiv2025

Mechanistic Variability in Corneal Nerve Recovery Linked to Injury Type

The cornea, a transparent tissue covering the eye, is essential for clear vision and represents the most densely innervated tissue in the body. Its extensive sensory innervation provides both sensory perception and crucial trophic support, maintaining corneal health and integrity. Disruption of corneal innervation leads to neurotrophic keratitis (NK), a pathological condition caused by ocular injury, surgical procedures, or underlying diseases. The limited understanding of NKs pathophysiological mechanisms has hindered the development of innovative therapeutic approaches. In this study, we comparatively analyzed corneal innervation morphogenesis and regeneration across two clinically relevant injury models, highlighting both commonalities and differences among these contexts. Our results demonstrate that corneal nerve morphogenesis and maturation span approximately 13 weeks, from embryonic day 12 (E12) through three months of age. Additionally, we observed that the specification of distinct nerve fiber types coincided temporally with a significant enhancement in corneal sensitivity. Furthermore, we found that the type of innervation loss--either via axotomy or abrasion--differentially affected corneal sensitivity and epithelial cell homeostasis. Importantly, the regeneration mechanisms following injury were also distinctly dependent on the type of nerve damage sustained. Collectively, these findings underscore both the shared characteristics and unique aspects inherent in each NK model, highlighting the necessity for tailored therapeutic strategies specific to individual patterns of corneal innervation disruption.

neuroscience↗

bioRxiv2024

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

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.

pathology↗

bioRxiv2022

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

Corneal blindness is the fourth leading cause of blindness worldwide. Since the corneal epithelium is constantly renewed, non-integrative gene transfer cannot be used to treat corneal diseases. In numerous of these diseases, the tear film has been reported to be defective. Tears are a complex biological fluid secreted by the lacrimal apparatus. Their composition is modulated according to the context. For instance, after a corneal wound, the lacrimal gland secretes reflex tears, which contain specific growth factors supporting the wound healing process. In specific pathological contexts, such as dry eye diseases, the tear composition can support neither corneal homeostasis, nor wound healing. Here, we propose to use the lacrimal gland as bioreactor to produce and secrete specific factors to support corneal physiology. In this study, we used an AAV2/9-mediated gene transfer to supplement the tear film. First, we demonstrate that a single injection of AAV2/9 is sufficient to transduce all epithelial cell types of the lacrimal gland efficiently and widely. Then, we show that lacrimal gland physiology and corneal integrity are maintained after the injection of an AAV2/9-mediated nerve growth factor expression in the lacrimal gland. Remarkably, this injection induces an important and long-lasting secretion of this growth factor in the tear film. Altogether, our findings provide a new clinically applicable approach to tackle corneal blindness.

physiology↗