Effect of desiccating stress on mouse meibomian gland function.
OBJECTIVE
Mice 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.


METHODS
Ten 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).


RESULTS
Desiccating 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.


CONCLUSIONS
These 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.
Gavin Herbert Eye Institute, Irvine, CA, USA; Beckman Laser Institute and Medical Clinic, Irvine, CA, USA; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
Jeffrey L
JL
Suhalim
Gavin Herbert Eye Institute, Irvine, CA, USA.
Geraint J
GJ
Parfitt
Gavin Herbert Eye Institute, Irvine, CA, USA.
Yilu
Y
Xie
Cintia S
CS
De Paiva
Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Cintia S
CS
De Pavia
Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Stephen C
SC
Pflugfelder
Gavin Herbert Eye Institute, Irvine, CA, USA.
Tejas N
TN
Shah
Beckman Laser Institute and Medical Clinic, Irvine, CA, USA.
Eric O
EO
Potma
Gavin Herbert Eye Institute, Irvine, CA, USA.
Donald J
DJ
Brown
Gavin Herbert Eye Institute, Irvine, CA, USA; Department of Biomedical Engineering, University of California, Irvine, CA, USA. Electronic address: JJester@uci.edu.
James V
JV
Jester
D000818:Animals; D049109:Cell Proliferation; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003890:Desiccation / Q000379:methods*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D006813:Humidity; D050356:Lipid Metabolism; D008537:Meibomian Glands / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012601:Scopolamine / Q000494:pharmacology; D013059:Spectrum Analysis, Raman; D013312:Stress, Physiological
D018680:Cholinergic Antagonists; D005136:Eye Proteins; D012601:Scopolamine
evaporative dry eye; meibomian gland; nonlinear optical microscopy; stimulated Raman scattering