A Role for ELOVL4 in the Mouse Meibomian Gland and Sebocyte Cell Biology

PURPOSE. The meibum lipidome contains lipids with extremely long chain fatty acid (ELCFA) residues, longer than C-28. Particular lipids based on extremely long chain (O-acyl)-omega-hydroxy fatty acids (OAHFA) are found in all mammal meibum and are proposed to stabilize the tear film by forming the interphase between its lipid and aqueous sublayers. The enzyme ELOVL4 is required for synthesis of ELCFA. We investigated whether Stgd3 mice, harboring mutations in ELOVL4 that have been shown to decrease the levels of its biosynthetic lipid products, would represent a model system in which to define the role of such lipids in meibum. METHODS. Ocular phenotypes of wild-type mice were compared with those of Stgd3 mice. ELOVL4 expression in eyelid and back skin was characterized by immunohistochemical analysis. Anatomical changes within the eyelids of mutant mice were examined by hematoxylin and eosin staining of paraffin-embedded tissue. RESULTS. Mutant mice had increased eyelid blink rates, a reluctance to maintain their eyes fully open, protruding meibomian gland (MG) orifices, and anatomical changes within the MG. In wild-type mice, ELOVL4 was strongly expressed within the holocrine meibomian and sebaceous glands. The enzyme localized to structures encircling lipid deposits within cells in both the early and late stages of differentiation. No ELOVL4 was detected within the central meibomian duct. CONCLUSIONS. Stgd3 mice show changes that resemble clinical findings in patients with the evaporative type of dry eye disease, suggesting that further studies in this mouse model will provide a basis for better understanding of the causes of human dry eye.