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.

• Authors: Kanako Sawada, Miki Hiraoka, Akira Abe, Robert Kelly, James A Shayman, Hiroshi Ohguro
• Journal: Current eye research (Curr Eye Res) Vol. 42 Issue 4 Pg. 611-616 (04 2017) ISSN: 1460-2202 [Electronic] England
• PMID: 27612621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Glial Fibrillary Acidic Protein
• Lipopolysaccharides
• Ophthalmic Solutions
• glial fibrillary astrocytic protein, mouse
• Phospholipases A2

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Glial Fibrillary Acidic Protein (metabolism)
• Inflammation (chemically induced, enzymology)
• Intraocular Pressure (drug effects, physiology)
• Lipopolysaccharides (toxicity)
• Lysosomes (enzymology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ophthalmic Solutions
• Phospholipases A2 (deficiency, physiology)
• Retina (metabolism)
• Uveitis (chemically induced, enzymology)