Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy
Corneal confocal microscopy (CCM) is emerging as a tool for identifying small fiber neuropathy in both peripheral neuropathies and neurodegenerative disease of the central nervous system (CNS). The value of corneal nerves as biomarkers for efficacy of clinical interventions against small fiber neuro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/9/2307 |
| _version_ | 1797504292741971968 |
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| author | Corinne G. Jolivalt May Madi Han Annee Nguyen Fiona Desmond Carlos Henrique Alves Jesus Daniela C. Vasconselos Andrea Pedneault Natalie Sandlin Sage Dunne-Cerami Katie E. Frizzi Nigel A. Calcutt |
| author_facet | Corinne G. Jolivalt May Madi Han Annee Nguyen Fiona Desmond Carlos Henrique Alves Jesus Daniela C. Vasconselos Andrea Pedneault Natalie Sandlin Sage Dunne-Cerami Katie E. Frizzi Nigel A. Calcutt |
| author_sort | Corinne G. Jolivalt |
| collection | DOAJ |
| description | Corneal confocal microscopy (CCM) is emerging as a tool for identifying small fiber neuropathy in both peripheral neuropathies and neurodegenerative disease of the central nervous system (CNS). The value of corneal nerves as biomarkers for efficacy of clinical interventions against small fiber neuropathy and neurodegenerative disease is less clear but may be supported by preclinical studies of investigational agents. We, therefore, used diverse investigational agents to assess concordance of efficacy against corneal nerve loss and peripheral neuropathy in a mouse model of diabetes. Ocular delivery of the peptides ciliary neurotrophic factor (CNTF) or the glucagon-like peptide (GLP) analog exendin-4, both of which prevent diabetic neuropathy when given systemically, restored corneal nerve density within 2 weeks. Similarly, ocular delivery of the muscarinic receptor antagonist cyclopentolate protected corneal nerve density while concurrently reversing indices of systemic peripheral neuropathy. Conversely, systemic delivery of the muscarinic antagonist glycopyrrolate, but not gallamine, prevented multiple indices of systemic peripheral neuropathy and concurrently protected against corneal nerve loss. These data highlight the potential for use of corneal nerve quantification by confocal microscopy as a bridging assay between in vitro and whole animal assays in drug development programs for neuroprotectants and support its use as a biomarker of efficacy against peripheral neuropathy. |
| first_indexed | 2024-03-10T04:02:34Z |
| format | Article |
| id | doaj.art-91e679d3f0dc44f3ae639298a532433a |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T04:02:34Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-91e679d3f0dc44f3ae639298a532433a2023-11-23T08:30:28ZengMDPI AGJournal of Clinical Medicine2077-03832022-04-01119230710.3390/jcm11092307Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic NeuropathyCorinne G. Jolivalt0May Madi Han1Annee Nguyen2Fiona Desmond3Carlos Henrique Alves Jesus4Daniela C. Vasconselos5Andrea Pedneault6Natalie Sandlin7Sage Dunne-Cerami8Katie E. Frizzi9Nigel A. Calcutt10Department of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92093, USACorneal confocal microscopy (CCM) is emerging as a tool for identifying small fiber neuropathy in both peripheral neuropathies and neurodegenerative disease of the central nervous system (CNS). The value of corneal nerves as biomarkers for efficacy of clinical interventions against small fiber neuropathy and neurodegenerative disease is less clear but may be supported by preclinical studies of investigational agents. We, therefore, used diverse investigational agents to assess concordance of efficacy against corneal nerve loss and peripheral neuropathy in a mouse model of diabetes. Ocular delivery of the peptides ciliary neurotrophic factor (CNTF) or the glucagon-like peptide (GLP) analog exendin-4, both of which prevent diabetic neuropathy when given systemically, restored corneal nerve density within 2 weeks. Similarly, ocular delivery of the muscarinic receptor antagonist cyclopentolate protected corneal nerve density while concurrently reversing indices of systemic peripheral neuropathy. Conversely, systemic delivery of the muscarinic antagonist glycopyrrolate, but not gallamine, prevented multiple indices of systemic peripheral neuropathy and concurrently protected against corneal nerve loss. These data highlight the potential for use of corneal nerve quantification by confocal microscopy as a bridging assay between in vitro and whole animal assays in drug development programs for neuroprotectants and support its use as a biomarker of efficacy against peripheral neuropathy.https://www.mdpi.com/2077-0383/11/9/2307diabetic neuropathycorneal confocal microscopyCNTFGLP-1exendin-4muscarinic antagonist |
| spellingShingle | Corinne G. Jolivalt May Madi Han Annee Nguyen Fiona Desmond Carlos Henrique Alves Jesus Daniela C. Vasconselos Andrea Pedneault Natalie Sandlin Sage Dunne-Cerami Katie E. Frizzi Nigel A. Calcutt Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy Journal of Clinical Medicine diabetic neuropathy corneal confocal microscopy CNTF GLP-1 exendin-4 muscarinic antagonist |
| title | Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy |
| title_full | Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy |
| title_fullStr | Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy |
| title_full_unstemmed | Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy |
| title_short | Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy |
| title_sort | using corneal confocal microscopy to identify therapeutic agents for diabetic neuropathy |
| topic | diabetic neuropathy corneal confocal microscopy CNTF GLP-1 exendin-4 muscarinic antagonist |
| url | https://www.mdpi.com/2077-0383/11/9/2307 |
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