Human Tear Serotonin Levels Correlate with Symptoms and Signs of Dry Eye

Chhadva, Priyanka; Lee, Tinthu; Sarantopoulos, Constantine; Hackam, Abigail S.; McClellan, Allison L.; Felix, Elizabeth R.; Levitt, Roy C.; Galor, Anat

doi:10.1016/j.ophtha.2015.04.010

Cited by 59 publications

(55 citation statements)

References 44 publications

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“…Therefore, a significant increase in the serotonin level in mouse eyelids can alter tear composition and cause pathological disturbances in its microcirculation [36], which can lead to the development of the dry eye symptom characteristic of PD [37, 38]. Hence, special attention should be given to an evaluation of tear fluid composition for the development of a preclinical diagnosis of PD.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

Kim¹,

Павленко²,

Катаргина³

et al. 2018

Acta Naturae

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Parkinson’s disease (PD) is a systemic neurodegenerative condition caused by the death of dopaminergic neurons of the nigrostriatal system of the brain. This disease is diagnosed after most neurons have already been lost, which explains the low efficiency of treatment. Hope for increasing treatment efficiency rests in the development of new strategies for early diagnosis of PD based on a search for peripheral markers that appear as early changes in non-motor functions. Since impairment of the visual function is one of the manifestations of PD, the purpose of our work was to identify biochemical and physiological changes in a mouse’s eye and eyelid in models of preclinical (presymptomatic) and clinical (symptomatic) stages of PD. We found that the norepinephrine, dopamine, and serotonin levels in the mouse eye reduced not only in the model of the early clinical stage, but also in the model of preclinical stage, an indication that pathological changes in the monoaminergic systems of the brain had affected the eye even before the motor disorders emerged. Moreover, in both models of PD, mice had increased intraocular pressure, indicating the development of both metabolic and functional impairments, which can be used as diagnostic markers. Unlike in the eye, the serotonin level in the eyelid was increased in mice at both parkinsonism stages and in presymptomatic mice to a much higher extent than in symptomatic ones. Given that serotonin is involved in the regulation of lacrimal glands of the eyelid, an increase in its level in parkinsonian mice should alter the composition of tear fluid, which could serve as a diagnostic marker of early stage of PD. Thus, the changes in the metabolism of monoamines in the eye and eyelid observed in mice at the early stage of parkinsonism are accompanied by changes in the function of these structures and, therefore, can be used as diagnostic markers of the early stage of PD.

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Section: Discussionmentioning

confidence: 99%

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

Kim¹,

Павленко²,

Катаргина³

et al. 2018

Acta Naturae

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“…In the dry eye samples, an increase in glucose and lactate and a decrease in formic acid and N-acetylglucosamine levels were found. Increased levels of serotonin have been correlated with dry eye signs and symptoms and higher concentrations of this neuro-transmitter have been found in symptomatic ADDE tears compared to tears of symptomatic dry eye patients with normal tear production [549]. …”

Section: Biochemical Properties Of Tearsmentioning

confidence: 99%

TFOS DEWS II Tear Film Report

et al. 2017

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The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

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“…Patients using an SSRI have a 1.551-fold increased risk of DED compared with that of patients using other types of psychotropic medication or not using these medications. 10 Some studies 11 have also reported that patients with DED have higher tear serotonin levels. Therefore, DED caused by SSRIs should receive more attention.…”

mentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

Zhang

Yin

Yue

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Our study aimed 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 20 patients received placebo treatment. The serotonin, inflammatory cytokine, and proapoptotic protein levels were determined by using protein chip, qRT-PCR, and 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 by qRT-PCR, immunohistochemical staining, and ELISA. Human corneal epithelial cells were subjected to serotonin, a HTR antagonist, and/or an NF-jB signaling inhibitor. The inflammatory cytokine and proapoptotic protein levels were determined by qRT-PCR, Western blot analysis, and ELISA. The cell apoptosis rate was assessed by 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-1b and TNF-a 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 surface by increasing the tear serotonin levels. In addition, serotonin induced an inflammatory response and cell apoptosis in corneal epithelial cells by activating NF-jB signaling. CONCLUSIONS. SSRIs aggravate depression-associated DED via activating the NF-jB pathway. The antagonist of HTRs or the inhibitor of NF-jB signaling presents a potential therapeutic strategy for depression-associated DED. (Trial registration number, ChiCTR1800015592).

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Human Tear Serotonin Levels Correlate with Symptoms and Signs of Dry Eye

Cited by 59 publications

References 44 publications

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism

TFOS DEWS II Tear Film Report

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

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