Optimization of individualized faricimab dosing for patients with diabetic macular edema: Protocol for the SWAN open-label, single-arm clinical trial.

PURPOSE: In patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals. METHODS: SWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 µm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan. RESULTS: The primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events. CONCLUSIONS: The SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems.

Alteration of treatment choices and the visual prognosis for diabetic macular edema in the era of anti-VEGF drugs: Analysis of the STREAT-DME 2 study.

PURPOSE: To assess the real-world outcome of best-corrected visual acuity (BCVA) following 2-year intervention for treatment-naïve diabetic macular edema (DME) since the approval of anti-vascular endothelial growth factor (VEGF) therapy. METHODS: A total of 1,780 treatment-naïve eyes with DME for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final BCVA, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated. RESULTS: Over a 2-year period, BCVA improved annually, finally reaching 7 letters. The proportion of eyes in which good vision was maintained (BCVA >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%. CONCLUSION: Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for DME. These findings reflect the evolution of DME treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time.

LncRNA-MM2P regulates retinal neovascularization through M2 macrophage polarization.

The study aims to investigate the effects and potential mechanisms of lncRNA-MM2P on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). The OIR model was established in C57BL/6J mice. RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) from mice were used for in vitro studies. RT-qPCR was used to analyze the expressions of lncRNA and mRNAs. The protein expression levels were determined by western blotting. The size of avascular areas and neovascular tufts were assessed based on isolectin B4 immunofluorescence staining images. The human retinal endothelial cells (HRECs) were used to evaluate the proliferation, migration, and tube formation of endothelial cells. The expression of lncRNA-MM2P was significantly upregulated from P17 to P25 in OIR retinas. Knockdown of lncRNA-MM2P levels in vivo led to a significant reduction in the neovascular tufts and avascular areas in the retinas of OIR mice. Knockdown of lncRNA-MM2P levels in vitro suppressed the expression of M2 markers in macrophages. Moreover, we found a significant inhibition of avascular areas and neovascular tufts in OIR mice injected intravitreally with M2 macrophages treated by shRNA-MM2P. The cellular functions of proliferation, migration, and tube formation were significantly attenuated in HRECs cultured with a supernatant of shRNA-MM2P-treated M2 macrophages. Our results indicate that lncRNA-MM2P regulates retinal neovascularization by inducing M2 polarization of macrophages in OIR mice. Therefore, lncRNA-MM2P may be a potential molecular target for immunoregulation of retinal neovascularization.

Relationship Between Fluoroquinolone Resistance and Mutations in the Quinolone Resistance-Determining Region in Corynebacterium macginleyi.

Purpose: The purpose of this study was to investigate the bacterial composition in the conjunctiva and to determine the relationship between fluoroquinolone resistance and mutations in the quinolone resistance-determining region (QRDR) in Corynebacterium macginleyi (C. macginleyi). Methods: Bacteria isolated from conjunctival swabs of patients awaiting ophthalmic surgery or patients with presumed keratoconjunctivitis were included in this study. For C. macginleyi isolates from 49 samples, the minimum inhibitory concentrations (MICs) of second- to fourth-generation fluoroquinolones were determined by broth microdilution. Additionally, we determined the sequence of the QRDR in the gyrA gene of C. macginleyi-positive isolates by direct sequencing and investigated the relationship between the QRDR mutation and the MICs of fluoroquinolones for C. macginleyi. Results: Among 423 eyes of 296 preoperative patients who underwent conjunctival culture testing, 105 eyes of 89 patients were culture-positive, and among 148 eyes of 147 patients with keratoconjunctivitis, 55 eyes of 54 patients were culture-positive. C. macginleyi accounted for the largest proportion of cultured organisms (34.8%). C. macginleyi-positive isolates were found in 45 eyes of 37 preoperative patients and in 4 eyes of 4 patients with keratoconjunctivitis. Direct sequencing revealed that 91.8% of C. macginleyi-positive isolates had amino acid mutations in the QRDR and 95.5% of mutations were found at Ser-87 and Asp-91. Isolates harboring double mutations at Ser-87 and Asp-91 were resistant to second- to fourth-generation fluoroquinolones. One isolate with double mutations at Ser-87 and Ala-88 but no mutation in Asp-91 showed intermediate susceptibility to moxifloxacin, a fourth-generation fluoroquinolone. Conclusions: C. macginleyi isolated from conjunctiva harboring QRDR amino acid mutations were resistant to second- to fourth-generation fluoroquinolones.

Association of Undercorrection With Residual Proinflammatory Gene Expressions and Clinical Outcomes After Medial Open Wedge Proximal Tibial Osteotomy.

BACKGROUND: Accumulating evidence suggests that synovial inflammation plays a pivotal role in knee osteoarthritis. Although biomechanical findings have shown that medial open-wedge proximal tibial osteotomy (OWPTO) decreases medial compartment loading by correcting knee alignment, the relationship between knee alignment and synovial inflammation in the biological microenvironment has not yet been elucidated. PURPOSES: To investigate the relationship between preoperative and postoperative knee alignment and synovial gene expression and to determine the cutoff point of postoperative knee alignment at which gene expression of synovial inflammation improves. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 36 patients with osteoarthritis who underwent OWPTO between June 2018 and May 2020 were enrolled. Synovial tissue was collected from affected knees during initial OWPTO and plate removal surgeries, and gene expression associated with the pathogenesis of osteoarthritis in the synovial tissue was investigated using real-time polymerase chain reaction. The correlation between weightbearing line ratio (WBLR) and synovial gene expression was determined. Receiver operating characteristic curve analysis was used to determine the cutoff values of WBLR for improving gene expression. The participants were divided into 2 groups, according to the cutoff values of their WBLR, and compared according to Knee injury and Osteoarthritis Outcome Score (KOOS) and synovial gene expression. RESULTS: Postoperative WBLR was correlated with gene expression of interleukin 1ß (IL1B) (ρ = -0.43; P = .008) and of interleukin 6 (IL6) (ρ = -0.41; P = .01). The cutoff value to predict improvement of IL6 was postoperative WBLR of 52%, with an area under the curve of 0.74 (P = .03). Patients with WBLR of <52% showed higher postoperative inflammatory gene (IL1B [P = .04] and IL6 [P = .03]) and inferior postoperative KOOS values compared with those with WBLR of >52%. CONCLUSION: The novel cutoff alignment for biological improvement after OWPTO in patients with medial compartment osteoarthritis was determined to be WBLR of 52%, and WBLR of <52% was associated with higher residual intra-articular inflammation and poor clinical outcomes. After accounting for surgical errors, the surgeon should set the target surgical alignment so that the postoperative WBLR does not fall below 52%.

Incidence and prognosis of taxane-induced macular edema: a retrospective study from the Japan Clinical REtina Study Group (J-CREST).

Macular edema is a known side effect of taxane-based anticancer drugs. We retrospectively investigated data from 11 centers between January 2016 and December 2021. Among 14,260 patients, 30 (0.21%) developed macular edema; from these, the number of cases associated with nab-paclitaxel was 16 (0.43%), significantly higher than the number of cases associated with paclitaxel or docetaxel (P < 0.01). Visual acuity (VA) and retinal choroidal change were examined in 27 patients, with a follow-up of at least 3 months. The patients' mean age was 67.2 years; 14 (51.3%) were male and four (14.8%) had unilateral onset. The mean interval between anticancer drug initiation and the first ophthalmology visit was 290.1 days. Among the 20 patients who discontinued anticancer drugs, VA and edema significantly improved 2 months after discontinuation (LogMAR VA: 0.50 vs. 0.28, central retinal thickness: 472.7 µm vs. 282.5 µm, both P < 0.01). No significant changes were observed in the central choroidal thickness. A correlation was found between duration of taxane treatment and VA immediately before discontinuation of anticancer drugs (ß = 0.00050; 95% confidence interval: 0.00036-0.00097; P < 0.05). Although taxane-induced macular edema is reversible, slower anticancer drug discontinuation worsened VA, highlighting the need for regular ophthalmologic evaluation during treatments.

Treatment Outcomes in Patients with Conjunctival Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Purpose: To report the outcomes of different therapies in patients with conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Patients and Methods: This retrospective study included patients diagnosed with conjunctival MALT lymphoma between August 2000 and April 2022. Patients were classified into three groups according to their treatment: an observation group, a radiation therapy (RT) group, and a rituximab group (rituximab with or without chemotherapy). We analyzed overall survival (OS), overall, local, and systemic relapse-free survival (RFS), and adverse events after treatment. Results: This study included 15 patients (22 eyes). The 10-year OS was 100%. The 2-, 5-, and 10-year overall RFS rates were 80.1%, 41.2%, and 41.2% in all patients, respectively. The 2- and 5-year local RFS rates in the observation group were 100% and 0%, respectively. The 2-, 5-, and 10-year local RFS rates were 87%, 87%, and 87% in the RT group and 83%, 67%, and 67% in the rituximab group, respectively. The 2- and 5-year systemic RFS rates in the observation group were both 100%, and the 2-, 5-, and 10-year systemic RFS rates were 92%, 55%, and 55% in the RT group, and 100%, 60%, and 60% in the rituximab group, respectively. After RT, 53.3% of the eyes developed cataracts and 75% of these were treated with cataract surgery. In addition, 53.3% of the eyes developed dry eyes and were treated with eye drops. Rituximab with or without chemotherapy resulted in some systemic adverse events, but these improved following symptomatic therapies. Conclusion: RT resulted in good local control of conjunctival MALT lymphoma; however, systemic relapse may occur during long-term follow-up. Local and/or systemic relapse may also occur during long-term follow-up in patients treated by observation or rituximab with or without chemotherapy. Patients with conjunctival MALT lymphoma should be followed-up carefully for as long as possible after treatment.

Principles of amyloplast replication in the ovule integuments of Arabidopsis thaliana.

Plastids in vascular plants have various differentiated forms, among which amyloplasts are crucial for starch storage and plant productivity. Despite the vast knowledge of the binary-fission mode of chloroplast division, our understanding of the replication of non-photosynthetic plastids, including amyloplasts, remains limited. Recent studies have suggested the involvement of stromules (stroma-filled tubules) in plastid replication when the division apparatus is faulty. However, details of the underlying mechanism(s) and their relevance to normal processes have yet to be elucidated. Here, we developed a live analysis system for studying amyloplast replication using Arabidopsis (Arabidopsis thaliana) ovule integuments. We showed the full sequence of amyloplast development and demonstrated that wild-type amyloplasts adopt three modes of replication, binary fission, multiple fission, and stromule-mediated fission, via multi-way placement of the FtsZ ring. The minE mutant, with severely inhibited chloroplast division, showed marked heterogeneity in amyloplast size, caused by size-dependent but wild-type modes of plastid fission. The dynamic properties of stromules distinguish the wild-type and minE phenotypes. In minE cells, extended stromules from giant amyloplasts acquired stability, allowing FtsZ ring assembly and constriction, as well as the growth of starch grains therein. Despite hyper-stromule formation, amyloplasts did not proliferate in the ftsZ null mutant. These data clarify the differences between amyloplast and chloroplast replication and demonstrate that the structural plasticity of amyloplasts underlies the multiplicity of their replication processes. Furthermore, this study shows that stromules can generate daughter plastids via the assembly of the FtsZ ring.

Melatonin: Unveiling the functions and implications in ocular health.

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.

Bibliometric evaluation of global trends and characteristics of RNA methylation during angiogenesis.

Background: RNA methylation is involved in major life processes. Angiogenesis is a normal phenomenon that occurs constantly in the bodies of all mammals, once it is aberrant or something goes wrong, it may lead to pathological changes. The bibliometric analysis could produce a comprehensive overview of RNA methylation during angiogenesis. Methods: The Web of Science Core Collection (WoSCC) database was used to screen publications about RNA methylation during angiogenesis from Jan 1, 2000 to Nov 24, 2022. Bibliometric and visualization analyses were conducted to understand publication trends by CiteSpace and VOSviewer. Results: In total, 382 publications from 2000 to 2022 were included in the bibliometric and visualization analyses. On the whole, the number of publications had exponential growth. China was the country and Sun Yat-Sen University was the university associated with the largest number of publications, although publications from the United Kingdom and Soochow University were currently having the strongest impact. Cancer was the most studied topic in this field, and N6-methyladenosine is the most studied RNA methylation type. Conclusion: There is a continuously increasing trend in publications related to RNA methylation and angiogenesis, which has attracted much attention, particularly since 2011. RNA methylation might be a promising target in the investigation of pathological angiogenesis and related disorders, which deserves further investigation.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

Ten-year outcomes of congenital cataract surgery performed within the first six months of life.

PURPOSE: To investigate the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. SETTING: 11 ophthalmic surgical sites in Japan. DESIGN: Retrospective chart review. METHODS: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. RESULTS: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this time frame. The incidence of secondary glaucoma was similar between groups while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. CONCLUSIONS: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of IOL with sophisticated surgical techniques shows promise even in congenital cataract surgery.

N6-methyladenosine methylation in ophthalmic diseases: From mechanisms to potential applications.

N6-methyladenosine (m6A) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in m6A modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that m6A modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding m6A modification in ophthalmic diseases, changes in m6A modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for m6A modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.

Clinical features of 26 cases of COVID-19-associated conjunctivitis.

PURPOSE: To explore the clinical features of COVID-19-associated conjunctivitis with the objective of preventing the spread of infection. STUDY DESIGN: Retrospective cohort study. METHODS: From March 2020 to March 2021, we retrospectively reviewed 26 (9.8%) consecutive COVID-19 patients with conjunctivitis among 282 COVID-19 cases admitted to our hospital. Clinical symptoms, onset date of conjunctivitis, time to patient recovery, and eye drop intervention were investigated. In addition, risk factors for developing conjunctivitis were statistically examined among 206 inpatients available for within 5 days of the onset. A multivariate analysis of conjunctivitis risk factors was performed. RESULTS: Among the 282 COVID-19 patients, 4 (1.4%) had conjunctival hyperemia as the primary symptom. The median time of onset was 4 days after the COVID-19 onset. Hyperemia was observed in all cases, but other ocular symptoms were rare. The median duration of hyperemia was 3 days. A multiple logistic regression analysis revealed that a young age (p=0.005) and current smoking habit (p=0.027) were independent risk factors for conjunctivitis after COVID-19. CONCLUSIONS: COVID-19-associated conjunctivitis is rare in the elderly and strongly associated with a history of smoking. It often occurs in the early stages of infection, and while hyperemia is recognized as a clinical symptom, other ocular symptoms are rare or non-existent. Many cases recover within a short time.

Long-term surgical outcomes of pediatric cataract-multivariate analysis of prognostic factors.

We assessed the 10-year postoperative outcomes of pediatric cataract patients who underwent surgery at the age of 6 years or younger. A retrospective review of medical charts was conducted for 457 eyes of 277 patients, with the age at surgery averaging 1.3 ± 1.5 years (mean ± SD) and the follow-up duration averaging 12.8 ± 2.4 years (ranging from 10 to 17 years). The cohort included 250 eyes of 125 cases with bilateral aphakia (age at surgery 0.5 ± 0.8 years), 110 eyes of 55 cases with bilateral pseudophakia (1.9 ± 1.6 years), 42 cases with unilateral aphakia (1.1 ± 1.3 years), and 55 cases with unilateral pseudophakia (2.6 ± 1.7). A forward stepwise multiple regression analysis revealed that the best-corrected visual acuity at the final visit was significantly associated with laterality of cataract (with bilateral cases showing better results compared to unilateral cases), presence of systemic comorbidities, presence of ocular comorbidities, development of glaucoma, and phakic status (with better results in the pseudophakia group than the aphakia group). The age at surgery did not significantly affect visual acuity outcomes. A multiple logistic regression analysis demonstrated that the incidence of secondary glaucoma was significantly linked to younger age at surgery, phakic status (higher in aphakic than pseudophakic eyes), and presence of systemic comorbidities. In conclusion, after pediatric cataract surgery, final visual acuity was better in patients with bilateral cataracts, those treated with an intraocular lens, and cases without systemic or ocular comorbidities and secondary glaucoma. The development of secondary glaucoma was linked to younger age at surgery, aphakic status, and presence of systemic comorbidities.

Decreased Elastic Modulus of Knee Articular Cartilage Based on New Macroscopic Methods Accurately Represents Early Histological Findings of Degeneration.

OBJECTIVE: Ex vivo nanoindentation measurement has reported that elastic modulus decreases as cartilage degenerates, but no method has been established to macroscopically evaluate mechanical properties in vivo. The objective of this study was to evaluate the elastic modulus of knee joint cartilage based on macroscopic methods and to compare it with gross and histological findings of degeneration. DESIGN: Osteochondral sections were taken from 50 knees with osteoarthritis (average age, 75 years) undergoing total knee arthroplasty. The elastic modulus of the cartilage was measured with a specialized elasticity tester. Gross findings were recorded as International Cartilage Repair Society (ICRS) grade. Histological findings were graded as Mankin score and microscopic cartilage thickness measurement. RESULTS: In ICRS grades 0 to 2 knees with normal to moderate cartilage abnormalities, the elastic modulus of cartilage decreased significantly as cartilage degeneration progressed. The elastic modulus of cartilage was 12.2 ± 3.8 N/mm for ICRS grade 0, 6.3 ± 2.6 N/mm for ICRS grade 1, and 3.8 ± 2.4 N/mm for ICRS grade 2. Similarly, elastic modulus was correlated with Mankin score (r = -0.51, P < 0.001). Multiple regression analyses showed that increased Mankin score is the most relevant factor associated with decreased elastic modulus of the cartilage (t-value, -4.53; P < 0.001), followed by increased histological thickness of the cartilage (t-value, -3.15; P = 0.002). CONCLUSIONS: Mechanical properties of damaged knee cartilage assessed with new macroscopic methods are strongly correlated with histological findings. The method has potential to become a nondestructive diagnostic modality for early cartilage damage in the clinical setting.

Progress and prospects of gene therapy in ophthalmology from 2000 to 2022: A bibliometric analysis.

Background: Gene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. Methods: A total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. Results: The annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. Conclusion: This study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.

Exosomal non-coding RNAs in angiogenesis: Functions, mechanisms and potential clinical applications.

Exosomes are extracellular vesicles that can be produced by most cells. Exosomes act as important intermediaries in intercellular communication, and participate in a variety of biological activities between cells. Non-coding RNAs (ncRNAs) usually refer to RNAs that do not encode proteins. Although ncRNAs have no protein-coding capacity, they are able to regulate gene expression at multiple levels. Angiogenesis is the formation of new blood vessels from pre-existing vessels, which is an important physiological process. However, abnormal angiogenesis could induce many diseases such as atherosclerosis, diabetic retinopathy and cancer. Many studies have shown that ncRNAs can stably exist in exosomes and play a wide range of physiological and pathological roles including regulation of angiogenesis. In brief, some specific ncRNAs can be enriched in exosomes secreted by cells and absorbed by recipient cells through the exosome pathway, thus activating relevant signaling pathways in target cells and playing a role in regulating angiogenesis. In this review, we describe the physiological and pathological functions of exosomal ncRNAs in angiogenesis, summarize their role in angiogenesis-related diseases, and illustrate potential clinical applications like novel drug therapy strategies and diagnostic markers in exosome research as inspiration for future investigations.

The influence of Bouba- and Kiki-like shape on perceived taste of chocolate pieces.

In this paper, we present the findings of a study investigating the impact of shape on the taste perception of chocolate. Previous research has explored the influence of various sensory information on taste perception, but there has been little focus on the effect of food shape being eaten on taste perception. To explore this, we focused on the Bouba-Kiki effect, illustrating an interaction between shape and several modalities, and investigated the effect of Bouba- and Kiki-shaped (rounded and angular) foods eaten on taste perception. We utilized a 3D food printer to produce four different shapes of chocolate pieces based on the Bouba-Kiki. Participants tasted each piece and completed a chocolate flavor questionnaire. With Bayesian analysis, we determined that the Bouba-shaped chocolate pieces were perceived as sweeter than the Kiki-shaped ones, supporting earlier studies on crossmodal correspondences between shape and taste perception. However, there were no significant differences in ratings of other tastes, such as sourness and bitterness. Our research indicates that shape can affect taste perception during consumption and suggests that 3D food printers offer an opportunity to design specific shapes that influence taste experiences.