Hyperosmolar Saline Is a Proinflammatory Stress on the... : Eye & Contact Lens (original) (raw)

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Hyperosmolar Saline Is a Proinflammatory Stress on the Mouse Ocular Surface

Luo, Lihui M.D.; Li, De-Quan M.D., Ph.D.; Corrales, Rosa M. Ph.D.; Pflugfelder, Stephen C. M.D.

From the Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX.

Presented in part as an abstract at the annual meeting of the Association for Research in Vision and Ophthalmology, May 4–8, 2003, Fort Lauderdale, Florida.

Supported by NIH grant EY11915 (S.C.P.) from the National Eye Institute, an unrestricted grant from Research to Prevent Blindness, the Oshman Foundation, and the William Stamps Farish Fund.

Address correspondence and reprint requests to Dr. S.C. Pflugfelder, Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC-205, Houston, TX 77030; e-mail: [email protected]

Accepted February 16, 2005.

Abstract

Purpose.

To investigate whether hyperosmolar stress stimulates production of inflammatory mediators and activates the mitogen-activated protein kinase (MAPK) signaling pathways, c-jun n-terminal kinases (JNKs), extracellular-regulated kinases (ERKs), and p38 on the mouse ocular surface.

Methods.

129SvEv/CD-1 mixed mice were treated with a balanced salt solution (BSS) (305 mOsM) or a hyperosmotic saline solution (HOSS) (500 mOsM). Untreated age-matched mice were used as controls. The concentrations of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were measured by enzyme-linked immunosorbent assay. Gelatinase activity was determined by in situ zymography. Corneal and conjunctival epithelia were lysed for Western blot with MAPK antibodies or used for semiquantitative reverse transcription and polymerase chain reaction and gene array.

Results.

Compared with age-matched controls and mice treated with BSS, the concentration of IL-1β in tear fluid washings and the concentrations of IL-1β and TNF-α and gelatinolytic activity in the corneal and conjunctival epithelia were significantly increased in mice treated with HOSS for 2 days. The expressions of IL-1β, TNF-α, and matrix metalloproteinase 9 (MMP-9) messenger RNA by the corneal and conjunctival epithelia were also notably stimulated in mice treated with HOSS. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were slightly increased in mice treated with BSS, but markedly increased in mice treated with HOSS.

Conclusions.

These results show that the hyperosmolarity stimulates expression and production of IL-1β, TNF-α, and MMP-9 and activates JNK, ERK, and p38 MAPK signaling pathways on the mouse ocular surface. These findings suggest that hyperosmolar stress, as it may occur in dry eye, promotes ocular surface inflammation.