Thymosin ß4 Alleviates Autoimmune Dacryoadenitis via Suppressing Th17 Cell Response.

Purpose: We investigated the therapeutic effect of recombinant thymosin ß4 (rTß4) on rabbit autoimmune dacryoadenitis, an animal model of SS dry eye, and explore its mechanisms. Methods: Rabbits were treated topically with rTß4 or PBS solution after disease onset for 28 days, and clinical scores were determined by assessing tear secretion, break-up time, fluorescein, hematoxylin and eosin staining, and periodic acid-Schiff. The expression of inflammatory mediators in the lacrimal glands were measured by real-time PCR. The expression of T helper 17 (Th17) cell-related transcription factors and cytokines were detected by real-time PCR and Western blotting. The molecular mechanism underlying the effects of rTß4 on Th17 cell responses was investigated by Western blotting. Results: Topical administration of rTß4 after disease onset efficiently ameliorated the ocular surface inflammation and relieved the clinical symptoms. Further analysis revealed that rTß4 treatment significantly inhibited the expression of Th17-related genes (RORC, IL-17A, IL-17F, IL-1R1, IL-23R, and granulocyte-macrophage colony-stimulating factor) and IL-17 protein in lacrimal glands, and meanwhile decreased the inflammatory mediators expression. Mechanistically, we demonstrated that rTß4 repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3) both in vivo and in vitro. Activation of the STAT3 signal pathway by Colivelin partly reversed the suppressive effects of rTß4 on IL-17 expression in vitro. Conclusions: rTß4 could alleviate ongoing autoimmune dacryoadenitis in rabbits, probably by suppressing Th17 response via partly affecting the STAT3 pathway. These data may provide a new insight into the therapeutic effect and mechanism of rTß4 in dry eye associated with Sjögren's syndrome.

Analysis of the relationship between axial length, optic disc morphology, and regional variations in retinal vessel density in young adults with healthy eyes.

Purpose: To investigate the relationship between optic disc morphology, axial length, and regional distribution of retinal vessels in healthy eyes of young adults. Methods: Nine hundred and two healthy eyes were enrolled in this university-based, cross-sectional study. Spectral-domain optical coherence tomography angiography was used to measure the parapapillary retinal vessel density. We automated the process of calculating optic disc tilt and rotation by using a program written in Python. Relationships between optic disc rotation, optic disc tilt, parapapillary vessel density, and other ocular parameters were analyzed using regression models. Results: As axial length increased, optic disc morphology became more tilted and rotated inferiorly. The superficial vessel density (SVD) and radial peripapillary capillary density (RPCD) gradually decreased in all regions except for the temporal quadrant. Increased temporal SVD (OR [95% CI] = 1.081 [1.039, 1.124], p < 0.001), reduced nasal SVD (OR [95% CI] = 0.898 [0.861, 0.937], p < 0.01), and short relative lens position (OR [95% CI] = 0.126 [0.032, 0.495], p = 0.003) were significantly associated with the presence of a tilted optic disc. Inferior disc rotation was associated with decreased superior deep vessel density (DVD) and increased inferior DVD and temporal DVD after adjusting for sex and axial length. Conclusion: The tilted and rotated optic discs were associated with the distribution of SVD and DVD, respectively. We should fully consider the influence of optic disc morphology on parapapillary vessel density in eyes with myopia.

PPAR-α Agonist Fenofibrate Ameliorates Sjögren Syndrome-Like Dacryoadenitis by Modulating Th1/Th17 and Treg Cell Responses in NOD Mice.

Purpose: To investigate the effects and mechanisms of fenofibrate, a synthetic ligand of peroxisome proliferator-activated receptor α (PPAR-α), on autoimmune dacryoadenitis in a mouse model of Sjögren syndrome (SS) dry eye. Methods: Male nonobese diabetic (NOD) mice were fed chow with or without 0.03% fenofibrate for 8 weeks, and clinical scores were determined by assessing tear secretion, fluorescein, and hematoxylin and eosin staining. Intracellular IFN-γ, IL-17, and Foxp3 in CD4+ T cells were measured by flow cytometry. The expressions of Th1, Th17, and Treg cell-related transcription factors and cytokines were detected by real-time PCR. The levels of PPAR-α and liver X receptor ß (LXR-ß) were detected with real-time PCR and Western blotting. Results: Fenofibrate efficiently diminished the lymphocytic inflammation in lacrimal glands (LGs), increased tear secretion, and decreased corneal fluorescein staining in NOD mice. Meanwhile, treatment of fenofibrate evidently reduced the proportion of Th1 and Th17 cells and increased the proportion of Treg cells in vivo and vitro, together with decreased expression of T-bet, IFN-γ, RORγt, and IL-17, as well as increased expression of Foxp3 and TGF-ß1 in LGs. Furthermore, fenofibrate significantly upregulated the expressions of PPAR-α and LXR-ß at the protein and mRNA levels. Conclusions: Fenofibrate potently attenuated LG inflammation in a model of autoimmune dry eye, and this effect might partially result from regulating Th1/Th17/Treg cell responses by activating PPAR-α/LXR-ß signaling. These data suggest that fenofibrate may be a novel class of therapeutic agent for SS-associated dacryoadenitis.

Prevalence and inconformity of refractive errors and ocular biometry of 3573 medical university freshman students for 4 consecutive years.

AIM: To evaluate the prevalence of refractive errors and ocular biometry in 3573 freshman students at Tianjin Medical University for 4 consecutive years. METHODS: In this university-based, cross-sectional study, comprising 3573 students, visual acuity (VA), slit-lamp examination, non-cycloplegic auto-refraction, and ocular biometry were recorded. RESULTS: The prevalence of myopia increased annually, from 2017 to 2020 were 93.5%, 94.5%, 95.9%, and 96.2%, respectively (P=0.03), and the prevalence of high myopia was 25.7%, 26.9%, 28.6%, and 28.6%, respectively. Males tended to have a higher percentage of total astigmatism than females, with astigmatism ≥0.75 and ≥1.0 D criteria. The percentage of with-the-rule astigmatism, against-the-rule astigmatism, and oblique astigmatism was 90.3%, 5.8%, and 3.9%, respectively, with astigmatism ≥1.00 D criteria. The mean spherical equivalent, axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), corneal radius (CR), and lens position (LP) were 4.37±2.52 D, 25.28±1.24 mm, 539.49±34.98 µm, 3.31±0.34 mm, 3.47±0.21 mm, 7.8±0.28 mm, and 5.04±0.32 mm, respectively. With diopter increase in myopia, the AL became longer, CR became steeper, ACD became deeper, LT became thinner, and LP became more posterior (all P<0.01). Females had a shorter AL, thinner CCT, smaller CR, shallower ACD, thicker lens, and more anterior LP than males (P<0.01). The 64% of high myopia had AL≥26 mm, meanwhile, 5.8% mild myopia and 21.1% moderate myopia had AL≥26 mm. With AL≥26 mm, mild and moderate myopia compared to high myopia, AL was shorter (26.51±0.46 vs 26.87±0.70 mm), CR was larger (8.10±0.3 vs 7.85±0.23 mm) and LT was thinner (3.39±0.19 vs 3.45±0.19 mm, P<0.001). CONCLUSION: The prevalence of myopia and high myopia is significantly high in freshman students. The majority of astigmatism is with-the-rule. Inconformity of refractive errors and ocular biometry existed in some students. Attention should be paid to the ocular biometry of myopia.

Relationship Between Myopia and Other Risk Factors With Anxiety and Depression Among Chinese University Freshmen During the COVID-19 Pandemic.

Purpose: To investigate the association of myopia and other risk factors with anxiety and depression among Chinese university freshmen during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This cross-sectional study was conducted at the Tianjin Medical University from October 2020 to December 2020. Ophthalmic examination of the eyes was performed by an experienced ophthalmologist. Detailed information on depression, anxiety, and other risk factors was collected via the Self-rating Anxiety Scale and Self-rating Depression Scale. Results: The overall prevalence of anxiety and depression in our study was 10.34 and 25.13%, respectively. The prevalence of myopia and high myopia as 92.02 and 26.7%, respectively. There were significant associations between anxiety and spectacle power [odds ratios (OR) = 0.89; 95% CI: 0.81-0.98, P = 0.019], sphere equivalent (OR = 0.89; 95% CI: 0.81- 0.98, P = 0.025), sleep time (OR = 0.53; 95% CI: 0.35-0.79, P = 0.002), and body mass index (OR = 0.93; 95% CI: 0.86-0.99, P = 0.047). In the multivariable linear regression models, spectacle power (ß = -0.43; 95% CI: -0.68 to -0.19, P = 0.001) and sphere equivalent (ß = -0.36; 95% CI: -0.60 to -0.11, P = 0.005) were negatively associated with anxiety scores, whereas axial length (ß = 0.54; 95% CI: 0.02-1.07, P = 0.044) was positively correlated with anxiety scores. Every 1 h decrease in sleep time was associated with a 0.12-point increase in depression score. Conclusion: Myopia was associated with anxiety and anxiety scores. The greater the degree of myopia, the higher the anxiety score. However, myopia was not found to be associated with depression. The results highlight the importance of providing psychological support to students with myopia during the COVID-19 pandemic.