Marginal Vitamin A Deficiency Affects the Expression Levels and Localization of Retinoic Acid Receptor and Retinoid X Receptor in Rats Meibomian Gland

Abstract

Purpose: To assess the effects of marginal vitamin A deficiency (MVAD) on rat Meibomian gland morphology as well as retinoic acid receptor (RAR) and retinoid X receptor (RXR) amounts and localization.

Methods: Eight adult female rats were randomized into MVAD and vitamin A normal (VAN) groups, and fed vitamin A-deficient and normal control diets, respectively, for 3 weeks before mating. At postnatal week 4 (P4w), eight newborn animals in both groups were euthanized, respectively. Then, serum retinol levels were analyzed. Meibomian glands from P4w animals were further assessed upon hematoxylin and eosin staining. RAR and RXR gene and protein expression amounts were detected by real time polymerase chain reaction (qRT-PCR), immunofluorescence and western blotting, respectively.

Results: Secretory cell nuclei had reduced areas, while the multilayered squamous epithelium of the ductule was overtly thinner in MVAD rats compared with VAN animals. RXR-α showed highest mRNA amounts among all RA receptors; compared with control values, RXR-α showed overtly decreased mRNA amounts in animals with MVAD. In addition, compared with normal rats, MVAD rats had starkly lower RXR-α and RXR-γ expression levels. Furthermore, only the RXR-α protein was detected in the nucleus of cells forming the multilayered squamous epithelium of the ductule in VAN rats.

Conclusion: RARs and RXRs may be involved in the regulation of Meibomian gland function. RXR-α and 9-cis RA signaling affects Meibomian gland function, and the mechanisms of retinoids on secretory cells and the ductule epithelium may differ.

Abbreviations: MVAD: marginal vitamin A deficiency; RAR: retinoic acid receptor; RXR: retinoid X receptor; VAN: vitamin A normal; RA: retinoic acid; RAREs: retinoic acid responsive elements; HPLC: high performance liquid chromatography; atRA: all-trans retinoic acid; MGD: Meibomian gland dysfunction; CRABPs: cellular retinoic acid-binding proteins.

Keywords: Meibomian gland; Retinoic acid receptor; Retinoid X receptor; marginal vitamin A deficiency.