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.

Thinning of the Lamina Cribrosa and Deep Layer Microvascular Dropout in Patients With Open Angle Glaucoma and High Myopia.

PRCIS: Lamina cribrosa (LC) thinning (thickness of ≤128.00 µm) helps to distinguish open angle glaucoma from high myopia, which was associated with the presence of microvasculature dropout and elevated intraocular pressure. PURPOSE: The purpose of this study was to analyze the factors associated with LC thickness in highly myopic eyes with and without open angle glaucoma. METHODS: In total, 240 highly myopic eyes with γ-zones (194 eyes without and 46 eyes with open angle glaucoma) were examined, and the LC center, externally oblique border, an abrupt change of scleral curvature (scleral step), deep layer microvasculature dropout and global retinal nerve fiber layer thickness were investigated on optical coherence tomography and optical coherence tomography angiography. RESULTS: LC were thinner in highly myopic open angle glaucoma compared with high myopia alone (107.76±9.86 vs. 137.07±18.51 µm, P <0.001), which was associated with deep layer microvasculature dropout and elevated intraocular pressure. The areas under the receiver operating characteristic curve for detecting open angle glaucoma from the LC thickness was 0.964, which was statistically higher ( P <0.05) than from the global retinal nerve fiber layer thickness (0.921) and vertical cup-to-disc ratio (0.902). A LC thickness cutoff value of 128 µm provided 100% sensitivity for detecting open angle glaucoma with 84% specificity. CONCLUSIONS: Highly myopic eyes with open angle glaucoma appear to have a thinner LC, which was associated with elevated intraocular pressure and deep layer microvasculature dropout. LC thinning (≤128.00 µm) helps distinguish open angle glaucoma from high myopia with an abnormal retinal nerve fiber layer thickness distribution and unclear shallow disc cupping.

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.