Prolonged Ocular Inflammation in Endotoxin-Induced Uveitis in Lysosomal Phospholipase A2-Deficient Mice

ABSTRACT

Purpose: The goal of present study was to elucidate the pathophysiological roles of lysosomal phospholipase A2 (LPLA2) in intraocular pressure (IOP) levels and ocular inflammation.

Methods: C57BL/6 (wild-type) and LPLA2-deficient mice with C57BL/6 background were employed. The IOPs were compared between wild-type and LPLA2-deficient mice during their aging, after topical administration of antiglaucoma medications such as travoprost, dorzolamide, or timolol maleate, or after induction of endotoxin-induced uveitis (EIU) using lipopolysaccharide (LPS). Concerning the EIU, ocular inflammation was also evaluated by immunohistochemical analysis by the anti-glial fibrillary acidic protein (GFAP) antibody.

Results: The LPLA2-deficient mice showed higher IOP levels than the wild-type mice until 2 months of age (P = 1.60E-06); in older mice there was no difference between the two groups. Significant differences in the IOP changes between groups in young mice were seen after administration of 0.5% timolol (P < 0.05). Upon induction of EIU by LPS, compared with wild-type mice (P < 0.05), IOPs were significantly elevated in LPLA2-deficient mice at maximum levels of the ocular inflammation (48 h). Immunohistochemical analysis indicated that LPLA2-deficient mice showed more prolonged expression of GFAP at the inner plexiform layer and inner nuclear layer by EIU than that found in the wild-type mice (P < 0.05).

Conclusions: These results confirm that LPLA2 plays a significant role in the control of IOP during mouse ocular development or with ocular inflammation by facilitating the digestion of intraocular insoluble materials.

KEYWORDS:

• Antiglaucoma medicines
• endotoxin-induced uveitis
• intraocular pressure
• lysosomal phospholipase A2
• mice

Acknowledgments

We would like to express our appreciation to Dr. Kimura and Dr. Yamaguchi in the division of morphological research at Sapporo Medical University for their histological work, and to Mr. Ito and Mr. Takeda in the image and media support section at Sapporo Medical University Hospital for their technical support.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This work was supported by a grant from the Japan Society for the Promotion of Science (JSPS KAKENHI) (Grant number: 26462665).

Additional information

Funding

This work was supported by a grant from the Japan Society for the Promotion of Science (JSPS KAKENHI) (Grant number: 26462665).