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Effect of Desiccating Stress on Mouse Meibomian Gland Function
Authors:Jeffrey L Suhalim  Geraint J Parfitt  Yilu Xie  Cintia S De Paiva  Stephen C Pflugfelder  Tejas N Shah  Eric O Potma  Donald J Brown  James V Jester
Institution:1. Gavin Herbert Eye Institute, Irvine, CA, USA;2. Beckman Laser Institute and Medical Clinic, Irvine, CA, USA;3. Department of Biomedical Engineering, University of California, Irvine, CA, USA;4. Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA;1. Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan;2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;3. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan;4. Department of Public Health, China Medical University, Taichung, Taiwan;5. Department of Ophthalmology, Taipei City Hospital Zhongxing Branch, Taipei, Taiwan;6. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan;1. Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA;2. Miami Veteran Affairs Medical Center, Miami, Florida, USA;3. Florida Lions Ocular Pathology Laboratory, Miami, Florida, USA
Abstract:PurposeMice exposed to standardized desiccating environmental stress to induce dry eye-like symptoms have been used as a model to study the underlying mechanisms of evaporative dry eye. While studies have shown marked inflammatory and immune changes, the effect of such stress on meibomian gland function remains largely unknown. We sought to evaluate the effects of desiccating stress on meibocyte proliferation and meibum quality.MethodsTen mice were treated with scopolamine and subjected to a drafty low humidity environment (30-35%). Five and ten days after treatment, eyelids were harvested and cryosections stained with Ki67 antibody to identify cycling cells. Sections were also imaged using stimulated Raman scattering (SRS) microscopy to characterize the gland compositional changes by detecting the vibrational signatures of methylene (lipid) and amide-I (protein).ResultsDesiccating stress caused a 3-fold increase in basal acinar cell proliferation from 18.3 ± 11.1% in untreated mice to 64.4 ± 19.9% and 66.6 ± 13.4% after 5 and 10 days exposure, respectively (P < .001). In addition, SRS analysis showed a wider variation in the protein-to-lipid ratio throughout the gland, suggesting alterations in meibocyte differentiation and lipid synthesis.ConclusionsThese data are consistent with a model that a desiccating environment may have a direct effect on meibomian gland function, leading to a significant increase in basal acinar cell proliferation, abnormal meibocyte differentiation, and altered lipid production.
Keywords:evaporative dry eye  meibomian gland  nonlinear optical microscopy  stimulated Raman scattering
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