Corneal Neurotization and Novel Medical Therapies for Neurotrophic Keratopathy

Rosenblatt, Tatiana R.; Sears, Connie Martin; Park, Ji Kwan; Kossler, Andrea L

doi:10.1007/s40135-020-00254-w

Cited by 5 publications

(4 citation statements)

References 93 publications

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“…In line, we performed a detailed surgical dissection of the cutaneous branch of the mylohyoid nerve and quantified its total axon composition, which has not been conducted in the rat. Overall, this data may be helpful in various experimental models for surgical nerve reconstruction models: the supraorbital and infraorbital nerves may be used for corneal neurotization (Catapano et al, 2018 ; Rosenblatt et al, 2020 ) as well as for sensory protection of cross-face nerve grafts for facial reanimation (Placheta et al, 2015b ; Catapano et al, 2016 ) and the mylohyoid nerve has been proposed as a donor nerve for facial nerve reconstruction (Tubbs et al, 2007 ). A better understanding of the neurophysiological processes occurring as a result of the reconstructive procedures may optimize surgical outcomes in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Selective Denervation of the Facial Dermato-Muscular Complex in the Rat: Experimental Model and Anatomical Basis

et al. 2021

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The facial dermato-muscular system consists of highly specialized muscles tightly adhering to the overlaying skin and thus form a complex morphological conglomerate. This is the anatomical and functional basis for versatile facial expressions, which are essential for human social interaction. The neural innervation of the facial skin and muscles occurs via branches of the trigeminal and facial nerves. These are also the most commonly pathologically affected cranial nerves, often requiring surgical treatment. Hence, experimental models for researching these nerves and their pathologies are highly relevant to study pathophysiology and nerve regeneration. Experimental models for the distinctive investigation of the complex afferent and efferent interplay within facial structures are scarce. In this study, we established a robust surgical model for distinctive exploration of facial structures after complete elimination of afferent or efferent innervation in the rat. Animals were allocated into two groups according to the surgical procedure. In the first group, the facial nerve and in the second all distal cutaneous branches of the trigeminal nerve were transected unilaterally. All animals survived and no higher burden was caused by the procedures. Whisker pad movements were documented with video recordings 4 weeks after surgery and showed successful denervation. Whole-mount immunofluorescent staining of facial muscles was performed to visualize the innervation pattern of the neuromuscular junctions. Comprehensive quantitative analysis revealed large differences in afferent axon counts in the cutaneous branches of the trigeminal nerve. Axon number was the highest in the infraorbital nerve (28,625 ± 2,519), followed by the supraorbital nerve (2,131 ± 413), the mental nerve (3,062 ± 341), and the cutaneous branch of the mylohyoid nerve (343 ± 78). Overall, this surgical model is robust and reliable for distinctive surgical deafferentation or deefferentation of the face. It may be used for investigating cortical plasticity, the neurobiological mechanisms behind various clinically relevant conditions like facial paralysis or trigeminal neuralgia as well as local anesthesia in the face and oral cavity.

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Section: Discussionmentioning

confidence: 99%

Selective Denervation of the Facial Dermato-Muscular Complex in the Rat: Experimental Model and Anatomical Basis

et al. 2021

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“…These surgical-based interventions could lead to complications such as infection, tissue rejection, incomplete epithelization, and postoperative side effects [11]. Novel therapies such as nerve growth factors, neuroprotective agents, and gene therapy are also being investigated for their potential to promote corneal nerve regeneration and prevent further neurodegeneration [12].…”

Section: Current Treatments For Corneal Neurodegenerative Diseasesmentioning

confidence: 99%

Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders

Massoumi

Amin

Soleimani

et al. 2023

IJMS

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Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.

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“…These ulcers are characterised by an imbalance in the healing process, resulting in chronic progression that can lead to serious complications, including corneal perforation and loss of vision. Faced with this challenging scenario, the search for innovative therapeutic interventions becomes imperative [15]. Insulin, recognised for its fundamental role in glucose metabolism, has demonstrated properties beyond its traditional functions.…”

Section: Introductionmentioning

confidence: 99%

Use and Efficacy of Insulin Eye Drops in Neurotrophic Corneal Ulcers: A Systematic Literature Review

Amorim,

Filho,

Júnior

et al. 2024

JAMMR

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This research aimed to analyse the use and efficacy of insulin eye drops in the treatment of neurotrophic corneal ulcers by means of a systematic literature review. To this end, relevant studies found in various databases were analysed, including PubMed, Scopus, Science Direct, Scielo, Bireme, Google Scholar and Web of Science. The selected studies were assessed in terms of their objectives, methodology, results and conclusions, with the aim of providing a comprehensive understanding of the current state of evidence on the subject. From the articles by Serrano-Giménez et al. [1], Wang et al. [2] Jaworski et al ([3], Tong et al. [4], Khilji et al. [5], Moreker et al. [6], Soares et al. [7], CUARTERO-MARTINEZ et al. [8], Lorente-Pascua et al. [9], Erin et al. [10], Diaz-Valle et al [11], Dana et al. [12] and Ruiz-Lozano et al. [13], trends, knowledge gaps and recommendations for clinical practice and future research were identified. As a result, the studies analysed showed a variety of outcomes in relation to the efficacy and safety of insulin eye drops in the treatment of neurotrophic corneal ulcers. There was also a lack of standardisation in the methods used and the evaluation measures, highlighting the need for a more uniform approach in subsequent studies. The main trends identified indicate that insulin eye drops can be effective in treating corneal neurotrophic ulcers, especially in refractory stages. However, there is a need for further research to define more precise diagnostic criteria and more standardised assessment measures. In conclusion, this systematic review has provided a solid basis for future research into the use of insulin eye drops in the treatment of corneal neurotrophic ulcers. The recommendations resulting from this study have the potential to inform clinical practice and guide future research in this field, with the aim of improving these procedures for patients with this specific ophthalmological condition.

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Corneal Neurotization and Novel Medical Therapies for Neurotrophic Keratopathy

Cited by 5 publications

References 93 publications

Selective Denervation of the Facial Dermato-Muscular Complex in the Rat: Experimental Model and Anatomical Basis

Selective Denervation of the Facial Dermato-Muscular Complex in the Rat: Experimental Model and Anatomical Basis

Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders

Use and Efficacy of Insulin Eye Drops in Neurotrophic Corneal Ulcers: A Systematic Literature Review

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