Auswahl der wissenschaftlichen Literatur zum Thema „Cornée – Innervation“

La cornée est le tissu le plus densément innervé du corps humain. Cette innervation joue un rôle dans la régulation de la sécrétion du film lacrymal et exerce un rôle trophique direct sur l'épithélium cornéen. Les axones cornéens expriment différents types de récepteurs et répondent à des fonctions de mécano-nocicepteurs, de récepteurs au froid ou de récepteurs polymodaux. Nous avons pu identifier de nouvelles lignées de souris transgéniques et les utiliser pour caractériser ces différentes populations axonales. L'innervation cornéenne débute à E12.5 chez la souris et est régulée par les molécules de Slits et de Sémaphorines et leurs récepteurs Robo et Plexines/Neuropilines respectivement. Nous avons pu étudier le rôle de ces deux familles dans le développement de l'innervation cornéenne. Les mutants Slits et Robos présentent une réduction du nombre et de la taille des terminaisons axonales épithéliales cornéennes. A l'âge adulte, les mutants Robos présentent une dégénérescence précoce des terminaisons épithéliales. Les mutants plexine-A4 et Neuropiline-1 présentent à l'inverse une augmentation du nombre de divisions des troncs stromaux cornéens. A l'âge adulte les mutants Plexine-A4 retrouvent une organisation classique de l'innervation alors que les mutants Neuropiline-1 conservent la désorganisation de l'innervation cornéenne. Nous avons également étudié la régénération de l'innervation après lésions de grattage de l'épithélium cornéen. Nos résultats préliminaires semblent en faveur d'une augmentation de la régénération de l'innervation cornéenne chez les mutants Neuropiline-1<br>The cornea is the most densely innervated tissue in the entire body. Corneal innervation plays a role in regulating the secretion of lacrimal film and exerts a direct trophic role on the corneal epithelium. Corneal axons express different types of sensory receptors ranging between mechano-, thermo-, and polymodal nociceptors. We identified transgenic mouse lines to characterize these different axonal populations. Corneal innervation begins at E12.5 in mice and is regulated by a range of axon guidance cues such as Slits and Semaphorins, which respond to their receptors Robo and Plexin/Neuropillin respectively. We studied the role of these two families in the development of corneal innervation. The Slits and Robos mutants show a reduction in the number and size of the corneal epithelial nerves endings. In adult, Robos mutants exhibit early degeneration of the epithelial nerves endings. Plexin-A4 and Neuropilin-1 mutants, on the other hand, show an increase in the number of divisions of the corneal stromal nerve trunks. In adult, Plexin-A4 mutants regain a classical organization of innervation whereas Neuropilin-1 mutants retain the disorganization of corneal innervation. Following a lesion, corneal innervation is able to regenerate, however the axons never regain their initial morphology or complexity. Due to the increased corneal innervation observed in the Neuropilin-1 mutants, we wondered whether the regeneration of innervation after scrapping lesions of the corneal epithelium could be enhanced in Neuropilin-1 loss of function. Our preliminary results support an increase in corneal innervation regeneration in Neuropilin-1 mutants

La cornée, structure transparente et avasculaire située dans le segment antérieur de l'œil, est le tissu le plus innervé du corps humain. Elle reçoit principalement des entrées sensorielles de la branche ophtalmique du nerf trijumeau. Les axones cornéens se répartissent de la couche la plus profonde (stroma) à la couche la plus superficielle (épithélium) et présentent une organisation distincte en forme de spirale. De plus, les nerfs cornéens sont essentiels au maintien de l'homéostasie tissulaire en interagissant avec les cellules épithéliales qui libèrent des neuropeptides. Bien que les techniques d'immunomarquage standard aient précédemment donné un aperçu de la configuration des nerfs cornéens, l'organisation dynamique des axones cornéens au fil du temps et leur réponse aux lésions cornéennes chez les souris vivantes restent peu connues. Ici, nous tirons parti de la lignée transgénique de souris CGRP:GFP (Bouheraoua et al., 2019), dans laquelle les fibres C nociceptives de la cornée sont marquées, et nous réalisons une imagerie longitudinale en direct des nerfs cornéens en utilisant la microscopie à 2 photons (2P) et la microscopie confocale à disque tournant. En suivant la même zone de la cornée pendant des semaines ou des mois, nous avons constaté que les axones individuels sont très dynamiques. Ils sont plus organisés en central et présentent une plus grande complexité de ramification de la période postnatale (P25) à l'âge adulte. De plus, nous avons pu suivre les nerfs cornéens chez la souris depuis la troisième semaine postnatale jusqu'au vieillissement. Nous avons observé que les nerfs stromaux profonds restent constants dans le temps, alors que les nerfs les plus superficiels sont remodelés, ce qui suggère un comportement hautement dynamique des nerfs cornéens dans l'espace et dans le temps. En cas de lésion de l'épithélium cornéen, les nerfs cornéens se régénèrent dès 24 heures après la lésion, suivis d'une dégénérescence après 3-4 jours. Environ 6 jours après la lésion, les axones se régénèrent à partir du nerf stromal sous-jacent, revenant progressivement à leur distribution initiale. Parallèlement, nous avons mis au point un protocole d'ablation au laser 2P pour effectuer une axotomie dans les nerfs stromaux et étudier l'intéraction entre les cellules neuronales et immunitaires dans la cornée. Nous avons pu suivre la dynamique des interactions entre les axones et les cellules immunitaires chez les souris Cx3cr1CreER;RosaTomCGRP:GFP. Après l'axotomie, les cellules immunitaires interagissaient spécifiquement avec les nerfs cornéens et restaient en contact les jours suivants. En résumé, nos résultats fournissent de nouvelles informations sur la plasticité des axones cornéens et leur potentiel de régénération, suggérant l'importance des cellules immunitaires en cas de lésion. Des études futures sont nécessaires pour mieux comprendre le mécanisme fondamental dans des conditions pathologiques<br>The cornea, a transparent and avascular structure located in the anterior segment of the eye, is the most innervated tissue in the human body. It mainly receives sensory inputs from the ophthalmic branch of the trigeminal nerve. Corneal axons distribute from the deepest layer (stroma) to the superficial layer (epithelium), and they exhibit a distinct spiral-like organization. Moreover, corneal nerves are essential in maintaining tissue homeostasis by interacting with epithelial cells releasing neuropeptides.Although standard immunostaining techniques have previously provided insights into corneal nerve patterning, the dynamic organization of corneal axons over time and their response to corneal injuries in live mice is still elusive. Here, we take advantage of CGRP:GFP mouse transgenic line (Bouheraoua et al., 2019), in which the corneal nociceptive C-fibers are labeled, and perform longitudinal live imaging on corneal nerves using 2-Photon (2P) and confocal spinning disk microscopy. By tracking the same area of the cornea over weeks to months, we found that single axons are highly dynamic. They become more centrally organized and exhibit higher branching complexity from the postnatal period (P25) to adulthood. Moreover, we were able to track the corneal nerves in mice from the third postnatal week until aging. We observed that the deep stromal nerves remain constant over time, while the most superficial nerves are remodeled, suggesting a highly dynamic behavior of corneal nerves in space and time.In case of lesion to the corneal epithelium, corneal nerves regenerate already 24 hours post-lesion, followed by subsequent degeneration after 3-4 days. Approximately 6 days post-lesion, axons regenerate from the underlying stromal nerve gradually returning to their initial distribution. Furthermore, we developed a 2P laser ablation protocol to perform axotomy in the stromal nerves and investigate the cross-talk between neuronal and immune cells in the cornea. We were able to follow the dynamics of the interactions between axons and immune cells in Cx3cr1CreER;RosaTomCGRP:GFP mice. After axotomy, immune cells specifically interacted with the corneal nerves, remaining in contact in the following days. In summary, our findings provide new insights into the plasticity of corneal axons and their regenerative potential, suggesting the importance of immune cells in case of lesion. Future studies are necessary to better understand the fundamental mechanism in pathological conditions

Apres avoir rapporte les principales caracteristiques fonctionnelles de la corne dorsale de la moelle epinere du rat, nous presentons une etude morpho-fonctionnelle du systeme serotonergique bulbo-spinal. Les recepteurs serotonergiques medullaires sont etudies par radioautographie. La plasticite de l'innervation serotonergique de la corne dorsale, en reponse a une modification des afferences primaires, est etudiee sur trois modeles experimentaux: capsaicine, rhizotomie et rats arhtritiques. La confrontation des resultats obtenus chez les animaux intacts et experimentaux, permetent de conclure que l'innervation serotonergique de la corne dorsale presente une grande specificite dans la topographie et dans les recepteurs qui lui correspondent. La plasticite du systeme, en revanche, conduirait a une structure finale plus uniforme dont il reste a savoir si elle s'exprime egalement au niveau fonctionnel

INTRODUCTION: The cornea forms the anterior-most barrier of the eye, consisting of a non-keratinized pseudostratified squamous epithelium, a collagen-based stroma, and an endothelium. It is completely avascular, yet the most densely innervated structure in the human body. The sensory nerves project from the ophthalmic branch of the trigeminal cranial nerve into the limbal/stromal interface. From there, the nerves branch and ascend into Bowman’s membrane, a basal lamina delineating the epithelium from the stroma, and project into the epithelium as free nerve endings. Injury to the corneal epithelium can potentially lead to impaired vision if the wound healing process is not properly initiated. Immediately after injury, nucleotides such as ATP are released and bind to purinergic receptors known to be located in epithelial cell membranes, thereby initiating epithelial cell migration to close the wound. Malfunctions in the interactions between the corneal nerves and their epithelial counterparts during the wound healing process are thought to contribute to the attenuated wound healing characteristic of diabetes. However, the precise nature of these interactions, how they facilitate wound healing, and how they are impaired in diabetes, is not well understood. OBJECTIVES: Previously, our lab has shown that a member of purinergic family receptors (P2X7) is localized in the basal epithelial cells and becomes relocated to the leading edge of the wound after injury. When the relocation is inhibited, migration is attenuated. Additionally, it is known that diabetic mouse models display slower wound healing rates. The present study has three aims: (1) to replicate the characteristic sub-basal whorl organization of the corneal nerves in organ-cultured corneas; (2) to elucidate the connections between patterns of corneal innervation and purinergic receptor expression; and (3) to understand how these patterns interact to facilitate normal wound healing and how these interactions are disrupted in a diabetic model. METHODS: Our approach was to use immunohistochemistry of dissected mouse and to visualize the tissue using confocal microscopy. Sensory innervation profiles from diet induced obesity (DIO) mouse corneas and their wildtype C57Bl6 counterparts were compared in unwounded and wounded tissue. To image the nerves a methanol fixation protocol was optimized to examine the sub-basal plexus and the apical nerves. Corneas were dissected, stained with beta III-tubulin, which identifies nerves, and with an antibody to the P2X7 purinergic receptor, which is expressed in the epithelium and nerves. Trephine induced epithelial abrasion injuries were made on separate DIO and control models to compare re-epithelialization and re-innervation between the diseased and healthy states. Corneas were imaged using a Zeiss LSM 700 laser scanning confocal microscope and optical images were taken through the cornea over a distance averaging 115 microns. Corneas were imaged using a macro tiling plugin, stitching 3x3 optical z-stacks into composite images. The 3x3 tiles were created to image the central whorl, as well as the peripheral nerve fibers. Co-localization of P2X7 and betaIII tubulin were determined by thresholding using ImageJ/FIJI software. RESULTS: The elegant organization of the centralized sub-basal whorl of the control mouse was disrupted in the DIO mouse cornea, appearing fragmented and incomplete. Analysis of 7.5 and 15 wk corneas showed the whorl to be present at 7.5 wks. Average apical nerve fiber projection length was decreased in DIO cornea. Yet, analyses at each epithelial layer demonstrated overall increased apical nerve density in the DIO corneas as compared to control while sub-basal nerve density decreased dramatically. Stromal nerves remained equivalent. P2X7 did co-localize to the large stromal nerve fibers but it was difficult to show the localization along the sub-basal nerve plexus. However in cross-section images, P2X7 displayed an intracellular polarity, and was present along the apical surface of the columnar basal epithelial cells lining the basement membrane. This localization may suggest the presence of P2X7 expressing sensory nerves, which may be ideally poised for communication with the basal cells after injury. CONCLUSIONS: These data support the hypothesis that there is indeed a difference between diabetic and control corneal innervation. While wound healing differences due to the interaction between sensory nerves and the localization of P2X7 in epithelium at the leading edge remain to be fully elucidated, the novel finding of P2X7 expression in corneal nerves confirms a potential role of purinergic receptor and nerve coordination in conducting the wound healing response.

Gracilis muscle is the most commonly used muscle in facial paralysis. Although the use of the contralateral buccal branches with the sural nerve graft as the recipient nerve provides spontaneous smiling, the main disadvantage is the weak contraction due to insufficient muscle innervation. Although the masseter nerve is a chewing muscle, it can be used as a recipient nerve to provide a strong contraction. However, postoperative adaptation of the brain is required to ensure spontaneous smiling. In this article, I will evaluate the results of the postoperative third-year results of 11 patients with partial thickness gracilis muscle. I carried on the masseter recipient nerve for oral corner reanimation in facial paralysis.

Emotion in the brain generated by subcortical brain circuits provides the foundation for creativity. Creativity is ultimately a higher brain process that is grounded in a variety of primal affective states of mind, mainly of the emotional variety. Of these emotional systems, the brain’s SEEKING system, arises from the medial forebrain bundle, which connects many regions of the lower brainstem and midbrain to the many higher regions of the brain, with especially rich innervation of the medial frontal cortex. This system, often known for prompting curiosity and exploration and giving rewards, is probably the most important brain engine for creativity. Animals share this core, primary emotional system with humans, despite the evolution of massive neocortices that are distinct for human creativity. But there are no intrinsic urges for creativity in the cortex itself. From an affective neuroscience perspective, the study of the emotional system in animal models can significantly serve for understanding the motivational sources of creativity in humans.

Abstract This paper covers the full range of core subjects tested in the FRCOphth Part 1 examination: optics, anatomy, physiology, pathology, pharmacology, genetics, investigations, and miscellaneous (biostatistics and evidence-based medicine). As well as ophthalmic subjects, this paper covers general physiology, general pathology, microbiology, biochemistry, and immunology. Several high-yield topics are covered. Ray diagrams are provided for the reflection of light by mirrors (convex and concave), Gullstrand’s schematic eye, and the reduced eye. An anatomical diagram displays the contents of the superior orbital fissure. The layers of the retina as seen on optical coherence tomography imaging are included, with a helpful mnemonic. Innervation and actions of the extraocular muscles are summarised in a table. The action potential is explained in a simple diagram. Histopathological slides displaying corneal dystrophies (lattice, macular, and granular) are included, with a helpful mnemonic. Electrodiagnostic tests are covered with useful figures. A flowchart for common statistical tests is provided

Abstract This paper covers the full range of core subjects tested in the FRCOphth Part 1 examination: optics, anatomy, physiology, pathology, pharmacology, genetics, investigations, and miscellaneous (biostatistics and evidence-based medicine). As well as ophthalmic subjects, this paper covers general physiology, general pathology, microbiology, biochemistry, and immunology. Several high-yield topics are covered. Ray diagrams are provided for the reflection of light by mirrors (convex and concave), Gullstrand’s schematic eye, and the reduced eye. An anatomical diagram displays the contents of the superior orbital fissure. The layers of the retina as seen on optical coherence tomography imaging are included, with a helpful mnemonic. Innervation and actions of the extraocular muscles are summarised in a table. The action potential is explained in a simple diagram. Histopathological slides displaying corneal dystrophies (lattice, macular, and granular) are included, with a helpful mnemonic. Electrodiagnostic tests are covered with useful figures. A flowchart for common statistical tests is provided.