Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites
Abstract Introduction The quantification of intraepithelial corneal basal nerve parameters by in vivo confocal microscopy represents a promising modality to identify the earliest manifestations of diabetic peripheral neuropathy. However, its diagnostic accuracy is hampered by its dependence on neuro...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Journal of Diabetes Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jdi.13974 |
| _version_ | 1797861905707040768 |
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| author | Joshua Machet Mijeong Park Alexander Richardson Michael Carnell Margaret A Mouat Nicola J Smith Nigel Turner Blake J Cochran Kerry‐Anne Rye Nick Di Girolamo |
| author_facet | Joshua Machet Mijeong Park Alexander Richardson Michael Carnell Margaret A Mouat Nicola J Smith Nigel Turner Blake J Cochran Kerry‐Anne Rye Nick Di Girolamo |
| author_sort | Joshua Machet |
| collection | DOAJ |
| description | Abstract Introduction The quantification of intraepithelial corneal basal nerve parameters by in vivo confocal microscopy represents a promising modality to identify the earliest manifestations of diabetic peripheral neuropathy. However, its diagnostic accuracy is hampered by its dependence on neuron length, with minimal consideration for other parameters, including the origin of these nerves, the corneal stromal‐epithelial nerve penetration sites. This study sought to utilize high‐resolution images of murine corneal nerves to analyze comprehensively the morphological changes associated with type 2 diabetes progression. Materials and Methods βIII‐Tubulin immunostained corneas from prediabetic and type 2 diabetic mice and their respective controls were imaged by scanning confocal microscopy and analyzed automatically for nerve parameters. Additionally, the number and distribution of penetration sites was manually ascertained and the average length of the axons exiting them was computed. Results The earliest detectable changes included a significant increase in nerve density (6.06 ± 0.41% vs 8.98 ± 1.99%, P = 0.03) and branching (2867.8 ± 271.3/mm2 vs 4912.1 ± 1475.3/mm2, P = 0.03), and in the number of penetration sites (258.80 ± 20.87 vs 422.60 ± 63.76, P = 0.0002) at 8 weeks of age. At 16 weeks, corneal innervation decreased, most notably in the periphery. The number of penetration sites remained significantly elevated relative to controls throughout the monitoring period. Similarly, prediabetic mice exhibited an increased number of penetration sites (242.2 ± 13.55 vs 305.6 ± 30.96, P = 0.003) without significant changes to the nerves. Conclusions Our data suggest that diabetic peripheral neuropathy may be preceded by a phase of neuron growth rather than regression, and that the peripheral cornea is more sensitive than the center for detecting changes in innervation. |
| first_indexed | 2024-04-09T22:10:48Z |
| format | Article |
| id | doaj.art-97976652a6524ec8becf296b04fdb5d4 |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-04-09T22:10:48Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-97976652a6524ec8becf296b04fdb5d42023-03-23T10:50:45ZengWileyJournal of Diabetes Investigation2040-11162040-11242023-04-0114459160110.1111/jdi.13974Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sitesJoshua Machet0Mijeong Park1Alexander Richardson2Michael Carnell3Margaret A Mouat4Nicola J Smith5Nigel Turner6Blake J Cochran7Kerry‐Anne Rye8Nick Di Girolamo9School of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaKatharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaSchool of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW AustraliaAbstract Introduction The quantification of intraepithelial corneal basal nerve parameters by in vivo confocal microscopy represents a promising modality to identify the earliest manifestations of diabetic peripheral neuropathy. However, its diagnostic accuracy is hampered by its dependence on neuron length, with minimal consideration for other parameters, including the origin of these nerves, the corneal stromal‐epithelial nerve penetration sites. This study sought to utilize high‐resolution images of murine corneal nerves to analyze comprehensively the morphological changes associated with type 2 diabetes progression. Materials and Methods βIII‐Tubulin immunostained corneas from prediabetic and type 2 diabetic mice and their respective controls were imaged by scanning confocal microscopy and analyzed automatically for nerve parameters. Additionally, the number and distribution of penetration sites was manually ascertained and the average length of the axons exiting them was computed. Results The earliest detectable changes included a significant increase in nerve density (6.06 ± 0.41% vs 8.98 ± 1.99%, P = 0.03) and branching (2867.8 ± 271.3/mm2 vs 4912.1 ± 1475.3/mm2, P = 0.03), and in the number of penetration sites (258.80 ± 20.87 vs 422.60 ± 63.76, P = 0.0002) at 8 weeks of age. At 16 weeks, corneal innervation decreased, most notably in the periphery. The number of penetration sites remained significantly elevated relative to controls throughout the monitoring period. Similarly, prediabetic mice exhibited an increased number of penetration sites (242.2 ± 13.55 vs 305.6 ± 30.96, P = 0.003) without significant changes to the nerves. Conclusions Our data suggest that diabetic peripheral neuropathy may be preceded by a phase of neuron growth rather than regression, and that the peripheral cornea is more sensitive than the center for detecting changes in innervation.https://doi.org/10.1111/jdi.13974Corneal stromal‐epithelial nerve penetration sitesDiabetic peripheral neuropathyIntraepithelial corneal basal nerves |
| spellingShingle | Joshua Machet Mijeong Park Alexander Richardson Michael Carnell Margaret A Mouat Nicola J Smith Nigel Turner Blake J Cochran Kerry‐Anne Rye Nick Di Girolamo Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites Journal of Diabetes Investigation Corneal stromal‐epithelial nerve penetration sites Diabetic peripheral neuropathy Intraepithelial corneal basal nerves |
| title | Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites |
| title_full | Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites |
| title_fullStr | Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites |
| title_full_unstemmed | Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites |
| title_short | Type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal‐epithelial nerve penetration sites |
| title_sort | type 2 diabetes influences intraepithelial corneal nerve parameters and corneal stromal epithelial nerve penetration sites |
| topic | Corneal stromal‐epithelial nerve penetration sites Diabetic peripheral neuropathy Intraepithelial corneal basal nerves |
| url | https://doi.org/10.1111/jdi.13974 |
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