lncRNA TGFß2-AS1 promotes ECM production via TGF-ß2 in human trabecular meshwork cells.

Evidence indicates that long noncoding RNAs (lncRNAs) participate in the regulation of various physiological and pathological processes including organ fibrosis and eye-related diseases. The important pathological manifestations of open-angle glaucoma (OAG) are human trabecular meshwork cells (HTMCs) apoptosis and excessive deposition of extracellular matrix (ECM) components in TM, which can cause pathological changes in the outflow pathway. To investigate the role and regulation mechanism of lncRNA in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) followed by RNA sequencing and found that subsets of lncRNAs and mRNAs that closely associate with TGF-ß signaling are differentially regulated in these cells. We then constructed a network with the TGF-ß2 -colocalized and -coexpressed lncRNAs, to investigate the effects and regulatory mechanisms of the potential lncRNAs on ECM deposition in HTMCs. The gain-of-function and loss-of-function experiments demonstrated that lnc-TGFß2-AS1 promotes ECM production via TGF-ß2 in HTMC, suggesting that lnc-TGFß2-AS1 may be a potential glaucoma treatment target.

Biometric indicators of eyes with occult lens subluxation inducing secondary acute angle closure.

BACKGROUND: To compare the anterior biometrics in eyes with secondary acute angle closure induced by occult lens subluxation (ASAC-LS), misdiagnosed as acute primary angle closure (APAC) at the first visit with APAC, chronic primary angle closure glaucoma (CPACG), and cataract. METHODS: This retrospective case study included 17 eyes with angel closure due to occult LS, who were misdiagnosed as APAC on their first visit, 56 APAC eyes, 54 CPACG eyes, and 56 cataract eyes. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AD) and lens thickness (LT) were recorded. Lens position (LP), relative lens position (RLP), corrected lens position (CLP) were calculated. Quantitative data were subject to one-way analysis of variance and correlation analysis. Categorical data were analyzed using the chi-squared test. Receiver operating characteristic (ROC) curves were plotted to obtain a suitable cutoff value of ocular biometrics. RESULTS: The ASAC-LS patients had a longer ocular axial length than APAC and CPACG patients. Central corneal thickness of the ASAC-LS patients was not significantly different from APAC patients, but was significantly different from CPACG and cataract patients. The APAC patients had the smallest ACD, while the ASAC-LS patients had the smallest AD. The ASAC-LS patients had the largest lens thickness. According to ROC curve analysis, RLP, ACD, AD, CLP, LP had high power of discrimination. CONCLUSIONS: This study revealed that LS secondary PAC patients had a shallower AD, thicker CCT comparing to those of APAC, CPACG and cataract patients. For patients with acute angle-closure glaucoma, it is necessary to exclude lens zonula relaxation. TRIAL REGISTRATION: NCT03752710, retrospectively registered.

1α,25-dihydroxyvitamin D3 attenuates oxidative stress-induced damage in human trabecular meshwork cells by inhibiting TGFß-SMAD3-VDR pathway.

Evidence indicates that 1α, 25-dihydroxy vitamin D3 (1, 25-(OH)2D3) markedly reduces intraocular pressure (IOP) in nonhuman primates, while the biochemical mechanisms are unclear. To investigate the influence of oxidative stress on human trabecular meshwork cells (HTMCs) and the effect and regulatory mechanism of 1, 25-(OH)2D3 in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) and showed that 1, 25-(OH)2D3 could inhibit oxidative stress-induced apoptosis and reduce extracellular matrix (ECM) composition of HTMCs. Moreover, 1, 25-(OH)2D3 could attenuate H2O2-induced inflammation in HTMCs. Mechanistically, our findings revealed that H2O2-induced damage was mediated by the transforming growth factor-ß (TGF-ß)-SMAD3 pathway in HTMCs, and 1, 25-(OH)2D3 could protect HTMCs against oxidative stress through vitamin D receptor (VDR), which antagonises the effects of SMAD3. Overall, these findings define a mechanism by which 1, 25-(OH)2D3 reduces ECM accumulation and suppresses the TGF-ß-SMAD3-VDR pathway in HTMCs, thus protecting the cells from oxidative stress, suggesting 1, 25-(OH)2D3 might be a potential therapeutic for glaucoma.

Associations of vitamin D deficiency and vitamin D receptor (Cdx-2, Fok I, Bsm I and Taq I) polymorphisms with the risk of primary open-angle glaucoma.

BACKGROUND: Vitamin D deficiency and vitamin D receptor gene polymorphisms are known to be significantly associated with high myopia. Whether this genetic variant may impact primary open-angle glaucoma is largely unknown. This study investigated whether vitamin D receptor gene polymorphisms are altered in primary open-angle glaucoma subjects carrying the risk allele, and whether vitamin D deficiency is an important factor in the development of glaucoma. METHODS: Seventy-three POAG patients and 71 age-matched controls from the Han population were enrolled. Serum levels of 1a, 25-Dihydroxyvitamin D3 were measured by enzyme-linked immunoabsorbent assay. Vitamin D receptor polymorphisms (Cdx-2, Fok I, Bsm I and Taq I) were analyzed using real-time polymerase-chain reaction high resolution melting analysis. RESULTS: Serum levels of 1a, 25-Dihydroxyvitamin in primary open-angle glaucoma patients were lower than in age-matched controls. Statistical analysis revealed a significant difference in the allelic frequencies of the BsmI and TaqI genotypes between primary open-angle glaucoma patients and age-matched controls, while other polymorphisms did not show any significant differences. CONCLUSIONS: Vitamin D deficiency and the presence of the BsmI 'B' allele and the TaqI 't' allele are relevant risk factors in the development of glaucoma. TRIAL REGISTRATION: Clinical Trials.gov: NCT02539745 . The study was registered retrospectively on August 3rd, 2015. The first participant was enrolled on July 4th, 2013.

Diode laser transscleral cyclophotocoagulation followed by phacotrabeculectomy on medically unresponsive acute primary angle closure eyes: the long-term result.

BACKGROUND: To explore the intraocular pressure-lowering effect and complications of diode laser transscleral cyclophotocoagulation (DLTSC) followed by phacotrabeculectomy on medically unresponsive acute primary angle closure eyes. METHODS: Nine eyes of nine medically unresponsive acute primary angle closure patients were enrolled. All the patients underwent cyclophotocoagulation followed by phacotrabeculectomy to control the prolonged acute attack. Data were recorded prospectively and then analyzed retrospectively. The reduction in intraocular pressure, improvement of vision and the complications were evaluated. RESULTS: After DLTSC, the IOP of all the patients were reduced, but all were above 21 mmHg under topical anti-glaucoma medications. After phacotrabeculectomy, the IOP of all the patients was decreased. At the final visit, the vision of all the patients was improved and the IOP of all the patients was below 21 mmHg without anti-glaucoma medications. There were no complications during the DLTSC and phacotrabeculectomy. Uveitis was the common complications after the both procedures, which were resolved by medication treatment. CONCLUSION: Diode laser transscleral cyclophotocoagulation followed by phacotrabeculectomy is an alternative procedure to control the intraocular pressure of medically unresponsive acute primary angle closure eyes with few complications.

DL-3-n-butylphthalide Protected Retinal Müller Cells Dysfunction from Oxidative Stress.

Purpose: To observe the protective effects and underlying mechanisms of dl-3-n-butylphthalide (NBP) against H2O2-induced oxidative damage in retinal Müller cells. Methods: Cultured human Müller cell line (MIO-M1line) were exposed to H2O2 for 2 hours. Cell survival was evaluated by Calcein AM cell viability assay. Dichlorofluorescein diacetate (DCFDA) + endoplasmic reticulum (ER) red fluorescent probe (ER-Tracker Red) staining was used to observe the expression level of reactive oxygen species (ROS) in ER of cells. Mitochondrial membrane potential detection (JC-1) was used to observe cell membrane potential change and early apoptosis. Cell apoptosis was detected by Hoechst33258 staining. The expressions of Nrf2, HO-1 were documented by cell Immunofluorescence staining and Western blot analysis. Results: NBP effectively improved the survival ability of Müller cells shown by MTT assay. NBP effectively alleviated the morphological and apoptotic changes induced by H2O2 stimulation by Calcein AM assay, HE staining, Hoechst 33258, JC-1 staining. H2O2 induction increased the expression level of ROS, whereas, the treatment with NBP could remarkably lower the expression level of ROS. Cell immunofluorescence staining indicated that the fluorescence staining intensity of HO-1 in the NBP group was significantly higher than that in the control group. While the western blotting results showed that the expression level of HO-1 could be increased by NBP in a time-dependent manner. The translocation of Nrf2 in nuclei was observed within 2 h and Nrf2 was identified in nuclei for up to 48 h. Conclusions: Our study demonstrated that NBP had a protective effect on H2O2-induced cytotoxicity in retinal Müller cells in vitro and that it was a potent activator of Nrf2 and HO-1signaling.