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Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.
Lab Invest. 2015 Nov; 95(11):1305-18.LI

Abstract

Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14 days after corneal debridement may destabilize newly reinnervated sub-basal axons and lead to their retraction toward the periphery.

Authors+Show Affiliations

Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC, USA.Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC, USA.Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC, USA.Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC, USA. Physiology and Neuroscience Program, University of Maryland, College Park, MD, USA.Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC, USA.Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC, USA. Department of Ophthalmology, The George Washington University Medical School, Washington, DC, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26280222

Citation

Pajoohesh-Ganji, Ahdeah, et al. "Partial Denervation of Sub-basal Axons Persists Following Debridement Wounds to the Mouse Cornea." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 95, no. 11, 2015, pp. 1305-18.
Pajoohesh-Ganji A, Pal-Ghosh S, Tadvalkar G, et al. Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea. Lab Invest. 2015;95(11):1305-18.
Pajoohesh-Ganji, A., Pal-Ghosh, S., Tadvalkar, G., Kyne, B. M., Saban, D. R., & Stepp, M. A. (2015). Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea. Laboratory Investigation; a Journal of Technical Methods and Pathology, 95(11), 1305-18. https://doi.org/10.1038/labinvest.2015.113
Pajoohesh-Ganji A, et al. Partial Denervation of Sub-basal Axons Persists Following Debridement Wounds to the Mouse Cornea. Lab Invest. 2015;95(11):1305-18. PubMed PMID: 26280222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea. AU - Pajoohesh-Ganji,Ahdeah, AU - Pal-Ghosh,Sonali, AU - Tadvalkar,Gauri, AU - Kyne,Briana M, AU - Saban,Daniel R, AU - Stepp,Mary Ann, Y1 - 2015/08/17/ PY - 2015/03/13/received PY - 2015/06/18/revised PY - 2015/06/24/accepted PY - 2015/8/18/entrez PY - 2015/8/19/pubmed PY - 2016/2/18/medline SP - 1305 EP - 18 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 95 IS - 11 N2 - Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over time after three different types of injury. The mouse cornea is highly innervated with a dense array of sub-basal nerves that form a spiral called the vortex at the corneal center or apex; these nerves are readily detected within flat mounted corneas. After anesthesia, corneal epithelial cells were removed using either a dulled blade or a rotating burr within an area demarcated centrally with a 1.5 mm trephine. A third wound type, superficial trephination, involved demarcating the area with the 1.5 mm trephine but not removing cells. By 7 days after superficial trephination, sub-basal axon density returns to control levels; by 28 days the vortex reforms. Although axon density is similar to control 14 days after dulled blade and rotating burr wounding, defects in axon morphology at the corneal apex remain. After 14 days, axons retract from the center leaving the sub-basal axon density reduced by 37.2 and 36.8% at 28 days after dulled blade and rotating burr wounding, respectively, compared with control. Assessment of inflammation using flow cytometry shows that persistent inflammation is not a factor in the incomplete reinnervation. Expression of mRNAs encoding 22 regeneration-associated genes involved in axon targeting assessed by QPCR reveals that netrin-1 and ephrin signaling are altered after wounding. Subpopulations of corneal epithelial basal cells at the corneal apex stop expressing ki67 as early as 7 days after injury and by 14 and 28 days after wounding, many of these basal cells undergo apoptosis and die. Although sub-basal axons are restored to their normal density and morphology after superficial trephination, sub-basal axon recovery is partial after debridement wounds. The increase in corneal epithelial basal cell apoptosis at the apex observed at 14 days after corneal debridement may destabilize newly reinnervated sub-basal axons and lead to their retraction toward the periphery. SN - 1530-0307 UR - https://www.unboundmedicine.com/medline/citation/26280222/Partial_denervation_of_sub_basal_axons_persists_following_debridement_wounds_to_the_mouse_cornea_ L2 - https://doi.org/10.1038/labinvest.2015.113 DB - PRIME DP - Unbound Medicine ER -