Meibomian Gland Dysfunction Model in Hairless Mice Fed a Special Diet With Limited Lipid Content.
A novel meibomian gland dysfunction (MGD) model was developed to facilitate understanding of the pathophysiology of MGD and to evaluate treatment with azithromycin ophthalmic solution (azithromycin). MGD was induced in HR-1 hairless mice by feeding them a special diet with limited lipid content (HR-AD).



Male HR-1 hairless mice were fed an HR-AD diet for 16 weeks. Development of MGD was assessed by histopathology at 4-week intervals. The lid margin was observed by slit-lamp examination. After cessation of the HR-AD diet, the mice were fed a normal diet to restore normal eye conditions. Expression of cytokeratin 6 was determined by immunostaining. We evaluated the effects of topically applied azithromycin on the plugged orifice in this model.



After mice were fed the HR-AD diet, histopathology analysis showed hyperkeratinization of the ductal epithelium in the meibomian gland. Ductal hyperkeratinization resulted in the loss of acini, followed by atrophy of the gland. Slit-lamp examination revealed a markedly plugged orifice, telangiectasia, and a toothpaste-like meibum compared with that of a normal eyelid. Cessation of feeding with HR-AD ameliorated both the MGD signs and the expression of cytokeratin 6, restoring the tissue to a histologically normal state. Azithromycin treatment significantly decreased the number of plugged orifices and ameliorated atrophy, as revealed by histopathologic analysis.



We developed a novel model that mimics human MGD signs in HR-1 hairless mice fed an HR-AD diet. Azithromycin treatment led to therapeutic improvement in this model. This MGD model could be useful for the evaluation of drug candidates for MGD.
Research and Development Division Santen Pharmaceutical Co., Ltd., Osaka, Japan 2Department of Medical Bioengineering, Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
Hideki
H
Miyake
Research and Development Division Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Tomoko
T
Oda
Research and Development Division Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Osamu
O
Katsuta
Department of Medical Bioengineering, Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
Masaharu
M
Seno
Research and Development Division Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Masatsugu
M
Nakamura
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D017963:Azithromycin / Q000008:administration & dosage*; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004195:Disease Models, Animal; D005141:Eyelid Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D053553:Keratin-6 / Q000096:biosynthesis; D050356:Lipid Metabolism; D008297:Male; D008537:Meibomian Glands / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless
D000900:Anti-Bacterial Agents; D053553:Keratin-6; D017963:Azithromycin