Keratoconjunctivitis Sicca Modifies Epithelial Stem Cell Proliferation Kinetics in Conjunctiva

Abstract

The objective of this study was to examine the epithelial stem cell proliferation kinetics in a rat model with keratoconjunctivitis sicca (KCS). Wistar rats received a daily injection of 5-bromo-2-deoxyuridine (BrdU) at a dose of 5 mg/100 g of body weight for 2 weeks. Dry eye was induced in 2 groups of rats by subcutaneous injection of scopolamine and placed in a desiccating environment: The first group received dry eye treatment at the beginning of BrdU labeling for 2 weeks; the second group received dry eye treatment after BrdU labeling for 4 weeks. Rats receiving no dry eye treatment were used as controls. Aqueous tear production, tear clearance, and corneal barrier function of dry eye rats were compared with those of control rats. Ocular epithelial morphology and goblet cell density were also evaluated in histologic sections. One month after BrdU injection, epithelial stem cell proliferation kinetics was assessed by BrdU labeling. Significant decreases in tear fluid secretion and tear clearance were noted in rats 5 days after dry eye treatment, with significantly increased corneal carboxy fluorescein uptake. Changes in ocular surface epithelial morphology and significantly reduced density of conjunctival goblet cells were found in dry eye groups. The number of conjunctival BrdU label-retaining cells in the rats with dry eye was significantly decreased compared with control rats (P < 0.01 for both groups). Furthermore, BrdU labeling in the before dry eye induction group showed more label-retaining basal cells in the conjunctiva than labeling in the dry eye state group (P < 0.01). Experimentally induced KCS in rats causes significant modification of epithelial stem cell proliferation kinetics in conjunctiva. The modification of epithelial stem cell proliferation kinetics in conjunctiva may play a crucial role in the development of KCS and may be a therapeutic target for this condition.