Prolonged Ocular Inflammation in Endotoxin-Induced Uveitis in Lysosomal Phospholipase A2-Deficient Mice.
The goal of present study was to elucidate the pathophysiological roles of lysosomal phospholipase A2 (LPLA2) in intraocular pressure (IOP) levels and ocular inflammation.



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.



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).



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.
a Department of Ophthalmology , School of Medicine, Sapporo Medical University , Sapporo , Japan.
Kanako
K
Sawada
a Department of Ophthalmology , School of Medicine, Sapporo Medical University , Sapporo , Japan.
Miki
M
Hiraoka
a Department of Ophthalmology , School of Medicine, Sapporo Medical University , Sapporo , Japan.
Akira
A
Abe
b Division of Nephrology , Medical Center, University of Michigan , Ann Arbor , MI , USA.
Robert
R
Kelly
b Division of Nephrology , Medical Center, University of Michigan , Ann Arbor , MI , USA.
James A
JA
Shayman
a Department of Ophthalmology , School of Medicine, Sapporo Medical University , Sapporo , Japan.
Hiroshi
H
Ohguro
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009883:Ophthalmic Solutions; D054467:Phospholipases A2 / Q000172:deficiency / Q000502:physiology*; D012160:Retina / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000201:enzymology*
D000959:Antihypertensive Agents; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D009883:Ophthalmic Solutions; C528900:glial fibrillary astrocytic protein, mouse; D054467:Phospholipases A2
Antiglaucoma medicines; endotoxin-induced uveitis; intraocular pressure; lysosomal phospholipase A2; mice