Abstract
Purpose :
Our study aims to evaluate the side effects of selective serotonin reuptake inhibitors (SSRIs) on the ocular surface.
Methods :
Twenty patients with depression and dry eye disease (DED) were randomly picked to receive SSRI treatment, whereas another twenty patients received placebo treatment. The serotonin, inflammatory cytokine and proapoptotic proteinlevels were determined using protein chip,qRT-PCRand ELISA analyses. A rat depression model was established, and SSRIs were applied for 3 or 6 weeks. Tear production and corneal epithelial barrier function were evaluated. The serotonin and inflammatory cytokine levels were analyzed byqRT-PCR, immunohistochemical staining and ELISA. Human corneal epithelial cells were subjected to serotonin,a HTR antagonist and/or a NF-κB signaling inhibitor. The inflammatory cytokine and proapoptotic protein levels were determined by qRT-PCR, western blotting and ELISA. The cell apoptosis rate was enumerated using flow cytometry.
Results :
The SSRI group had higher tear serotonin levels and more serious inflammation and cell apoptosis on the ocular surface. In the rat depression model, depression decreased tear secretion and increased IL-1βand TNF-α production, whereas the serotonin, TLR2 and TLR4 levels were not increased. SSRI aggravated DED, disrupted the corneal epithelial barrier and promoted an inflammatory response on the ocular surfaceby increasing the tear serotonin levels.In addition, serotonin induced an inflammatory response and cell apoptosis in corneal epithelial cells by activating NF-κBsignaling.
Conclusions :
SSRIs aggravate depression-associated DED via activating the NF-κBpathway.The antagonist of HTRs or the inhibitor of NF-κB signaling presents a potential therapeutic strategy for depression-associative DED.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.