Tags

Type your tag names separated by a space and hit enter

Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1.
Invest Ophthalmol Vis Sci. 2017 10 01; 58(12):4959-4975.IO

Abstract

Purpose

To determine the impact of the loss of syndecan 1 (SDC1) on intraepithelial corneal nerves (ICNs) during homeostasis, aging, and in response to 1.5-mm trephine and debridement injury.

Methods

Whole-mount corneas are used to quantify ICN density and thickness over time after birth and in response to injury in SDC1-null and wild-type (WT) mice. High-resolution three-dimensional imaging is used to visualize intraepithelial nerve terminals (INTs), axon fragments, and lysosomes in corneal epithelial cells using antibodies against growth associated protein 43 (GAP43), βIII tubulin, and LAMP1. Quantitative PCR was performed to quantify expression of SDC1, SDC2, SDC3, and SDC4 in corneal epithelial mRNA. Phagocytosis was assessed by quantifying internalization of fluorescently labeled 1-μm latex beads.

Results

Intraepithelial corneal nerves innervate the corneas of SDC1-null mice more slowly. At 8 weeks, ICN density is less but thickness is greater. Apically projecting intraepithelial nerve terminals and lysosome-associated membrane glycoprotein 1 (LAMP1) are also reduced in unwounded SDC1-null corneas. Quantitative PCR and immunofluorescence studies show that SDC3 expression and localization are increased in SDC1-null ICNs. Wild-type and SDC1-null corneas lose ICN density and thickness as they age. Recovery of axon density and thickness after trephine but not debridement wounds is slower in SDC1-null corneas compared with WT. Experiments assessing phagocytosis show reduced bead internalization by SDC1-null epithelial cells.

Conclusions

Syndecan-1 deficiency alters ICN morphology and homeostasis during aging, reduces epithelial phagocytosis, and impairs reinnervation after trephine but not debridement injury. These data provide insight into the mechanisms used by sensory nerves to reinnervate after injury.

Authors+Show Affiliations

Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, D.C., United States.Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, D.C., United States.Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, D.C., United States. Department of Ophthalmology, The George Washington University Medical School, Washington, D.C., United States.

Pub Type(s)

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

Language

eng

PubMed ID

28973369

Citation

Pal-Ghosh, Sonali, et al. "Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1." Investigative Ophthalmology & Visual Science, vol. 58, no. 12, 2017, pp. 4959-4975.
Pal-Ghosh S, Tadvalkar G, Stepp MA. Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1. Invest Ophthalmol Vis Sci. 2017;58(12):4959-4975.
Pal-Ghosh, S., Tadvalkar, G., & Stepp, M. A. (2017). Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1. Investigative Ophthalmology & Visual Science, 58(12), 4959-4975. https://doi.org/10.1167/iovs.17-21531
Pal-Ghosh S, Tadvalkar G, Stepp MA. Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1. Invest Ophthalmol Vis Sci. 2017 10 1;58(12):4959-4975. PubMed PMID: 28973369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1. AU - Pal-Ghosh,Sonali, AU - Tadvalkar,Gauri, AU - Stepp,Mary Ann, PY - 2017/10/4/entrez PY - 2017/10/4/pubmed PY - 2017/10/7/medline SP - 4959 EP - 4975 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 58 IS - 12 N2 - Purpose: To determine the impact of the loss of syndecan 1 (SDC1) on intraepithelial corneal nerves (ICNs) during homeostasis, aging, and in response to 1.5-mm trephine and debridement injury. Methods: Whole-mount corneas are used to quantify ICN density and thickness over time after birth and in response to injury in SDC1-null and wild-type (WT) mice. High-resolution three-dimensional imaging is used to visualize intraepithelial nerve terminals (INTs), axon fragments, and lysosomes in corneal epithelial cells using antibodies against growth associated protein 43 (GAP43), βIII tubulin, and LAMP1. Quantitative PCR was performed to quantify expression of SDC1, SDC2, SDC3, and SDC4 in corneal epithelial mRNA. Phagocytosis was assessed by quantifying internalization of fluorescently labeled 1-μm latex beads. Results: Intraepithelial corneal nerves innervate the corneas of SDC1-null mice more slowly. At 8 weeks, ICN density is less but thickness is greater. Apically projecting intraepithelial nerve terminals and lysosome-associated membrane glycoprotein 1 (LAMP1) are also reduced in unwounded SDC1-null corneas. Quantitative PCR and immunofluorescence studies show that SDC3 expression and localization are increased in SDC1-null ICNs. Wild-type and SDC1-null corneas lose ICN density and thickness as they age. Recovery of axon density and thickness after trephine but not debridement wounds is slower in SDC1-null corneas compared with WT. Experiments assessing phagocytosis show reduced bead internalization by SDC1-null epithelial cells. Conclusions: Syndecan-1 deficiency alters ICN morphology and homeostasis during aging, reduces epithelial phagocytosis, and impairs reinnervation after trephine but not debridement injury. These data provide insight into the mechanisms used by sensory nerves to reinnervate after injury. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/28973369/Alterations_in_Corneal_Sensory_Nerves_During_Homeostasis_Aging_and_After_Injury_in_Mice_Lacking_the_Heparan_Sulfate_Proteoglycan_Syndecan_1_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.17-21531 DB - PRIME DP - Unbound Medicine ER -