The role of EZH2 in ocular diseases: a narrative review.

EZH2, acting as a catalytic subunit of PRC2 to catalyze lysine 27 in histone H3, induces the suppression of gene expression. EZH2 can regulate cell proliferation and differentiation of retinal progenitors, which are required for physiological retinal development. Meanwhile, an abnormal level of EZH2 has been observed in ocular tumors and other pathological tissues. This review summarizes the current knowledge on EZH2 in retinal development and ocular diseases, including inherited retinal diseases, ocular tumors, corneal injury, cataract, glaucoma, diabetic retinopathy and age-related retinal degeneration. We highlight the potential of targeting EZH2 as a precision therapeutic target in ocular diseases.

EZH2 is a protein that helps to regulate the activity of genes in cells. It works as a part of a complex called PRC2 to control a chemical group called lysine 27 in histone H3 and then inhibit the expression of genes. EZH2 is important for the normal development of the retina. Abnormal levels of EZH2 are associated with various eye diseases. This review summarizes the role of EZH2 in different ocular diseases and the potential mechanisms. Targeting EZH2 may be a novel way to treat or prevent ocular diseases.

Flipped Classroom Case Learning vs Traditional Lecture-Based Learning in Medical School Ophthalmology Education: A Randomized Trial.

PURPOSE: To address the problem of teaching noncore specialties, for which there is often limited teaching time and low student engagement, a flipped classroom case learning (FCCL) module was designed and implemented in a compulsory 5-day ophthalmology rotation for undergraduate medical students. The module consisted of a flipped classroom, online gamified clinical cases, and case-based learning. METHOD: Final-year medical students in a 5-day ophthalmology rotation were randomized to the FCCL or a traditional lecture-based (TLB) module. The outcomes of subjective assessments (student-rated anonymous Likert scale questionnaire, scale 1 to 5, and course and teaching evaluation, scale 1 to 6) and objective assessments (end-of-rotation and post-MBChB multiple-choice questions, scale 0 to 60) were compared between the 2 groups. RESULTS: Between May 2021 and June 2022, 216 students (108 in each group) completed the study. Compared with the TLB students, the students in the FCCL group rated various aspects of the course statistically significantly higher, including feeling more enthusiastic and engaged by the course and more encouraged to ask questions and participate in discussions (all P < .001). They also gave higher ratings for the instructional methods, course assignments, course outcomes, and course workload ( P < .001). They gave higher course and teaching evaluation scores to the tutors (5.7 ± 0.6 vs 5.0 ± 1.0, P < .001). The FCCL group scored higher than the TLB group on the end-of-rotation multiple-choice questions (53.6 ± 3.1 vs 51.8 ± 2.8, P < .001). When 32 FCCL students and 36 TLB students were reassessed approximately 20 weeks after the rotation, the FCCL group scored higher (40.3 ± 9.1) than the TLB group (34.3 ± 10.9, P = .018). CONCLUSIONS: Applying the FCCL module in ophthalmology teaching enhanced medical students' satisfaction, examination performance, and knowledge retention. A similar model may be suitable for other specialties.

Integrated Meta-omics Approaches To Understand the Microbiome of Spontaneous Fermentation of Traditional Chinese Pu-erh Tea.

The microbiome in fermentation has direct impacts on the quality of fermented foods and is of great scientific and commercial interest. Despite considerable effort to explain the microbial metabolism associated with food fermentation, the role of the microbiome in pu-erh tea fermentation remains unknown. Here, we applied integrated meta-omics approaches to characterize the microbiome in two repeated fermentations of pu-erh tea. Metabarcoding analysis of bacterial 16S rRNA genes showed a decrease in the proportion of Proteobacteria and an increase in the abundance of Firmicutes during fermentation. Metabarcoding analysis of fungal internal transcribed spacer (ITS) sequence demonstrated that Rasamsonia, Thermomyces, and Aspergillus were dominant at the intermediate stage, whereas Aspergillus was dominant at other stages in fermentation. Metaproteomics analysis assigned primary microbial metabolic activity to metabolism and identified microbial carbohydrate-active enzymes involved in the degradation of polysaccharides including cellulose, xylan, xyloglucan, pectin, starch, lignin, galactomannan, and chitin. Metabolomics and high-performance liquid chromatography analysis revealed that levels of phenolic compounds, including gallates, decreased whereas contents of gallic acid and ellagic acid significantly increased after fermentation (P < 0.05). The changes in levels of gallates and gallic acid were associated with the hydrolysis of tannase. Glycoside hydrolases, phenol 2-monooxygenase, salicylaldehyde dehydrogenase, salicylate 1-monooxygenase, catechol O-methyltransferase, catechol dioxygenase, and quercetin 2,3-dioxygenases were hypothesized to be related to oxidation, conversion, or degradation of phenolic compounds. We demonstrated microbiota in fermentation and their function in the production of enzymes related to the degradation of polysaccharides, and metabolism of phenolic compounds, resulting in changes in metabolite contents and the quality of pu-erh tea.IMPORTANCE Fermented foods play important roles in diets worldwide and account for approximately one-third of all foods and beverages consumed. To date, traditional fermentation has used spontaneous fermentation. The microbiome in fermentation has direct impacts on the quality and safety of fermented foods and contributes to the preservation of traditional methods. Here, we used an integrated meta-omics approach to study the microbiome in the fermentation of pu-erh tea, which is a well-known Chinese fermented food with a special flavor and healthful benefits. This study advanced the knowledge of microbiota, metabolites, and enzymes in the fermentation of pu-erh tea. These novel insights shed light onto the complex microbiome in pu-erh fermentation and highlight the power of integrated meta-omics approaches in understanding the microbiome in food fermentation ecosystems.

Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation.

Angiopoietin 2 (ANG2) is a proangiogenic cytokine which may have an implication in neovascular age related macular degeneration (nAMD). In 24 eyes of 24 subjects presenting with treatment naïve nAMD and 26 eyes of 26 control patients, aqueous humor samples were collected at the time of intervention (intravitreal injection of anti-vascular endothelial growth factor or cataract extraction). Best corrected visual acuity (BCVA) with and central macular thickness (CMT) using optical coherence tomography (OCT) were measured before each injection in the nAMD group. Aqueous cytokine levels were determined by immunoassay using a multiplex array (Quansys Biosciences, Logan, UT). Levels of ANG2 in the aqueous were significantly higher in nAMD patients than those of the control group (p < 0.0001), so were hepatocyte growth factor (HGF), interleukin-8 (IL-8) and tissue inhibitor of metalloproteinase 1 (TIMP 1), all with p < 0.001. ANG2 correlated with worse BCVA (r = 0.44, p-value = 0.027) and greater CMT (r = 0.66, p-value < 0.0001) on optical coherence tomography (OCT). ANG2 is upregulated in patients with nAMD and correlates with severity of disease at presentation.

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposome.

BACKGROUND: Topical transdermal gene delivery to the skin shows great potential for painless, non-invasive administration of vaccines and therapeutic agents. Interleukin (IL)-4 strategies have shown a good antipsoriatic effect in clinic trials. To date, no information has been acquired on the effectiveness of gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal penetration of murine IL-4 (mIL-4) using ultradeformable cationic liposome (UCL). METHODS: In the present study, we synthesized an UCL and determined a suitable formula for transdermally delivering plasmid DNA to mouse skin. We then tested the antipsoriatic efficacy in the K14-VEGF transgenic mouse model by transdermal delivery of mIL-4 using UCL. RESULTS: We found that plasmid DNA was transdermally delivered to vicinal sites of epidermis and hair follicles using this optimized formula. Plasmid DNA expression was detected in ear skin. Twenty-four hours after topical application, plasmid DNA was not detected in blood serum and liver, which may decrease the risk of insertion of promoter from plasmid to genomic DNA. Mice treated with UCL/mIL-4 displayed a mild psoriasis phenotype. Histological analysis of pathological score using the Baker scoring system revealed an antipsoriatic effect. Immunohistochemical analysis revealed that hyperplastic and inflamed vessels were suppressed. CONCLUSIONS: These observations provide evidence of antipsoriatic efficacy by topical transdermal delivery of mIL-4. Therefore, topical transdermal gene transfer is attractive and offers future potential for application in human patients with other dermatogic diseases.