Abstract
Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient’s daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation–induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.
Highlights
Ionizing radiation causes damage in normal tissues located in the field of radiation and induces both functional and morphological changes in glandular tissues, including the salivary gland, thryroid gland, and lacrimal gland (LG) [1,2,3]
Previous reports have revealed the associations between the pathogenesis of ocular damage in dry eye syndrome and cataracts and NFAT5 expression [10,11,15,16]
We observed a significant increase in the expression of NFAT5 in the LG at 2, 6, and 8 weeks after radiation, but the expression was decreased in a time-dependent manner (Figure 1)
Summary
Ionizing radiation causes damage in normal tissues located in the field of radiation and induces both functional and morphological changes in glandular tissues, including the salivary gland, thryroid gland, and lacrimal gland (LG) [1,2,3]. An alternative method of preventing and treating radiation-induced dry eye is needed, including clarifying the mechanism between radiation and lacrimal dysfunction of the ocular surface. Hyperosmolar stress is a key factor of dry eye syndrome, and NFAT5 has been shown to be induced and translocated to the nucleus in ocular tissue cells under hyperosmolar stress. Recent studies suppose this molecule may be an important gene regulation and cell survival factor in the hyperosmolar-stressed ocular surface [10,11], and the tonicity-independent stimulation of NFAT5 is crucial for tissue-specific functions such as enhanced cell survival, migration, and proliferation [9]. The relationship between NFAT5 and radiation-induced LG injury has not been mentioned
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