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Peripheral (not central) corneal epithelia contribute to the closure of an annular debridement injury.

ABSTRACT: Corneal epithelia have limited self-renewal and therefore reparative capacity. They are continuously replaced by transient amplifying cells which spawn from stem cells and migrate from the periphery. Because this view has recently been challenged, our goal was to resolve the conflict by giving mice annular injuries in different locations within the corneolimbal epithelium, then spatiotemporally fate-mapping cell behavior during healing. Under these conditions, elevated proliferation was observed in the periphery but not the center, and wounds predominantly resolved by centripetally migrating limbal epithelia. After wound closure, the central corneal epithelium was completely replaced by K14⁺ limbal-derived clones, an observation supported by high-resolution fluorescence imaging of genetically marked cells in organ-cultured corneas and via computational modeling. These results solidify the essential role of K14⁺ limbal epithelial stem cells for wound healing and refute the notion that stem cells exist within the central cornea and that their progeny have the capacity to migrate centrifugally.

SUBMITTER: Park M

PROVIDER: S-EPMC6936562 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Peripheral (not central) corneal epithelia contribute to the closure of an annular debridement injury.

Park Mijeong M Richardson Alexander A Pandzic Elvis E Lobo Erwin P EP Lyons J Guy JG Di Girolamo Nick N

Proceedings of the National Academy of Sciences of the United States of America 20191216 52

Corneal epithelia have limited self-renewal and therefore reparative capacity. They are continuously replaced by transient amplifying cells which spawn from stem cells and migrate from the periphery. Because this view has recently been challenged, our goal was to resolve the conflict by giving mice annular injuries in different locations within the corneolimbal epithelium, then spatiotemporally fate-mapping cell behavior during healing. Under these conditions, elevated proliferation was observed ...[more]

PMID: 31843909

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Project description:Background: Lumbar discectomy is a common surgical procedure in middle-aged adults. However, outcomes of lumbar discectomy among older adults are unclear. Methods: Lumbar discectomy patients with an annular defect ?6 mm width were randomized to receive additional implantation with a bone-anchored annular closure device (ACD, n=272) or no additional implantation (controls, n=278). Over 3 years follow-up, main outcomes were symptomatic reherniation, reoperation, and the percentage of patients who achieved the minimum clinically important difference (MCID) without a reoperation for leg pain, Oswestry Disability Index (ODI), SF-36 Physical Component Summary (PCS) score, and SF-36 Mental Component Summary (MCS) score. Results were compared between older (?60 years) and younger (<60 years) patients. We additionally analyzed data from two postmarket ACD registries to determine consistency of outcomes between the randomized trial and postmarket, real-world results. Results: Among all patients, older patients suffered from crippling or bed-bound preoperative disability more frequently than younger patients (57.9% vs 39.1%, p=0.03). Among controls, female sex, higher preoperative ODI, and current smoking status, but not age, were associated with greater risk of reherniation and reoperation. Compared to controls, the ACD group had lower risk of symptomatic reherniation (HR=0.45, p<0.001) and reoperation (HR=0.54, p=0.008), with risk reductions comparable in older vs younger patients. The percentage of patients achieving the MCID without a reoperation was higher in the ACD group for leg pain (81% vs 72%, p=0.04), ODI (82% vs 73%, p=0.03), PCS (85% vs 75%, p=0.01), and MCS (59% vs 46%, p=0.007), and this benefit was comparable in older versus younger patients. Comparable benefits in older patients were observed in the postmarket ACD registries. Conclusion: Outcomes with lumbar discectomy and additional bone-anchored ACD are superior to lumbar discectomy alone. Older patients derived similar benefits with additional bone-anchored ACD implantation as younger patients.

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Peripheral (not central) corneal epithelia contribute to the closure of an annular debridement injury.

Publications

Peripheral (not central) corneal epithelia contribute to the closure of an annular debridement injury.

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