Abstract 52: An Animal Model Of Corneal Neurotisation Using The Thy1-GFP+ Rat To Further Investigate How Reinnervation Influences Corneal Health
Notice bibliographique
Résumé
PURPOSE: Patients with corneal anaesthesia develop neurotrophic keratopathy, causing corneal scarring and vision loss. Corneal neurotisation restores sensation but it remains unknown whether donor nerves reinnervating the cornea contain neuromediators that are required for corneal epithelial maintenance and repair. Further investigation of the effect of neurotisation on corneal health requires an animal model in which tissue can be harvested for analysis. Here we describe a rat model of corneal neurotisation. METHODS:Thy1-GFP+ rats, which express green fluorescent protein in axons, were used to monitor corneal denervation and reinnervation. Parameters for the stereotactic electrocautery of the ophthalmic branch (V1) of cranial nerve V, which innervates the cornea, was determined using serial imaging of whole mount corneas at 1, 2 and 4 weeks to determine optimal parameters for corneal denervation. Blink reflexes were assessed to confirm corneal denervation. After establishing a method of corneal denervation, corneal neurotisation was accomplished using common peroneal (CP) and sural nerve grafts coapted to the contralateral infraorbital nerve. Four corneas were harvested 4 weeks after neurotisation and denervation to determine corneal nerve density and four corneas were retrograde labelled with 4% Fluorogold to determine whether reinnervating axons derived from the contralateral or ipsilateral trigeminal ganglion (TG). Neurotised corneas were compared with uninjured (normal) and denervated (injured) controls. CP and sural grafts were harvested for histomorphometry. RESULTS: Optimal corneal denervation was achieved by ablating V1 at the stereotactic coordinates (+ 1.5 mm, + 2.0 mm, 10 mm) with 3 W for 60s. Stereotactic electrocautery of V1 was well tolerated, however injury to the TG resulted in unacceptable morbidity. Corneal neurotisation using CP and sural nerve grafts was successful resulting in a significant increase in corneal axon density. Denervated corneas demonstrated minimal reinnervation after 4 weeks (2301 μm/mm2 ± 1347) and reinnervation was restricted to the peripheral stroma. Neurotised corneas exhibited significantly greater corneal nerve density (62872 μm/mm2 ± 12400; p < 0.0001), which extended to the central cornea and subbasal layer and was comparable to uninjured (normal) controls (46165 μm/mm2 ± 3965). Histomorphometry demonstrated significant growth of myelinated axons across the grafts. Retrograde-labelling of uninjured cornea controls labeled 478 ± 16 neurons in the ipsilateral TG innervating the cornea with no labeled neurons in the contralateral TG. In contrast, labelling of neurotised corneas demonstrated no labeled neurons in the ipsilateral TG (0 ± 0) with a significant number of labelled sensory neurons in the contralateral TG (353 ± 215), suggesting axons reinnervating the cornea after neurotisation derived from the donor grafts and contralateral face. CONCLUSION: The described animal model of corneal neurotisation is valuable to further investigate how reinnervation of the cornea using foreign donor nerves influences corneal epithelial health, including epithelial healing and protein expression.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».