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Cintia S. De Paiva, MD; Solherny B. Pangelinan, MD; Emmanuel Chang, MD, PhD; K.-C. Yoon, MD, PhD; William J. Farley, MS; De-Quan Li, MD, PhD; Stephen C. Pflugfelder, MD

Arch Ophthalmol. 2009;127(12):1625-1631.

Objective  To investigate the protective effects of c-Jun N-terminal kinase (JNK)–1 and -2 gene knockout (KO) on the corneal epithelial response to desiccating stress.

Methods  The C57BL/6, JNK1KO, and JNK2KO mice were subjected to desiccating stress (DS) for 5 days. The effects of DS on the corneal epithelium were evaluated by measuring corneal smoothness and permeability. Expression of matrix metalloproteinases (MMP)–1, MMP-9, and cornified envelope protein precursors (small proline-rich protein [SPRR]–1a, SPRR-2a, and involucrin) in the corneal epithelia was evaluated by immunostaining and real-time polymerase chain reaction. Collagenase and gelatinase activity in corneal sections as measured with in situ fluorescent assays.

Results  The JNK2KO mice had smoother corneal surfaces and less corneal barrier disruption in response to DS than JNK1KO mice and C57BL/6 wild-type control mice. The DS increased levels of MMP-1, MMP-9, SPRR-1a, SPRR-2a, involucrin immunoreactivity, and mRNA transcripts in the corneal epithelium of JNK1KO and C57BL/6 mice, but not in JNK2KO mice. Knockout of JNK2 prevented DS-induced increase in gelatinase and collagenase activity in the cornea.

Conclusion  The JNK2 protein appears to have an essential role in desiccation-induced corneal epithelial disease by stimulating production of MMP-1, MMP-9, and cornified envelope precursors.

Clinical Relevance  The JNK2 protein could be a novel therapeutic target in dry eye disease.

Author Affiliations: Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas (Drs De Paiva, Pangelinan, Chang, Li, and Pflugfelder, and Mr Farley); and Department of Ophthalmology, Chonnam National University Medical School, Dong-Gu, Gwangju, South Korea (Dr Yoon).

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