Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema.

AIM: To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide (TA) in treating diabetic macular edema (DME) and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection. METHODS: Totally 67 DME patients (67 eyes) and 30 cataract patients (32 eyes) were enrolled as the DME group and the control group, respectively. The DME group was divided into the aflibercept group (34 cases) and the aflibercept combined with TA group (combined group, 33 cases). The aqueous humor of both groups was collected during the study period. The aqueous levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) were detected using a microsphere suspension array technology (Luminex 200TM). Aqueous cytokines, best-corrected visual acuity (BCVA), central macular thickness (CMT), and complications before and after treatment were compared between the aflibercept group and combined group. RESULTS: The concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group (all P<0.01). After 1mo of surgery, the concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group (all P<0.01). The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment (P<0.01). However, the difference was not statistically significant after 3mo of treatment (P>0.05). CONCLUSION: The cytokines VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor of DME patients are significantly increased. Aflibercept and aflibercept combined with TA have good efficacy in DME patients, can effectively reduce CMT, improve the patient's vision, and have high safety. Aflibercept combined with TA can quickly down-regulate the aqueous humor cytokines and help to relieve macular edema rapidly. However, the long-term efficacy is comparable to that of aflibercept alone.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.

The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.

Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.

Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.

Bibliometric and visualization analysis of global research trends on immunosenescence (1970-2021).

BACKGROUND: Immunosenescence, the aging of the immune system, leads to a decline in the body's adaptability to the environment and plays an important role in various diseases. Immunosenescence has been widely studied in recent years. However, to date, no relevant bibliometric analyses have been conducted. This study aimed to analyze the foundation and frontiers of immunosenescence research through bibliometric analysis. METHODS: Articles and reviews on immunosenescence from 1970 to 2021 were obtained from the Web of Science Core Collection. Countries, institutions, authors, journals, references, and keywords were analyzed and visualized using VOSviewer and CiteSpace. The R language and Microsoft Excel 365 were used for statistical analyses. RESULTS: In total, 3763 publications were included in the study. The global literature on immunosenescence research has increased from 1970 to 2021. The United States was the most productive country with 1409 papers and the highest H-index. Italy had the highest average number of citations per article (58.50). Among the top 10 institutions, 50 % were in the United States. The University of California was the most productive institution, with 159 articles. Kroemer G, Franceschi C, Goronzy JJ, Solana R, and Fulop T were among the top 10 most productive and co-cited authors. Experimental Gerontology (n = 170) published the most papers on immunosenescence. The analysis of keywords found that current research focuses on "inflammaging", "gut microbiota", "cellular senescence", and "COVID-19". CONCLUSIONS: Immunosenescence research has increased over the years, and future cooperation and interaction between countries and institutions must be expanded. The connection between inflammaging, gut microbiota, age-related diseases, and immunosenescence is a current research priority. Individualized treatment of immunosenescence, reducing its negative effects, and promoting healthy longevity will become an emerging research direction.

Bibliometric and visual analyses of trends in the field of T cell exhaustion research: Findings from 2000 to 2022.

BACKGROUND: T cell exhaustion refers to a state wherein T cells become less functional as a result of their prolonged exposure to cognate antigens. A wealth of T cell exhaustion-focused research has been conducted in recent decades, transforming the current understanding of this biologically relevant process. However, there have not been any comprehensive bibliometric analyses to date focused on clarifying the T cell exhaustion-related research landscape. Here, a bibliometric analysis was thus conducted with the goal of better elucidating the current state of knowledge and emerging research hotspots in this field. METHODS: The Web of Science Core Collection was searched for articles and reviews related to T cell exhaustion, with the CiteSpace and VOSviewer programs then being employed to analyze the countries, institutions, authors, references, and keywords associated with studies in this research space. RESULTS: In total, 2676 studies were incorporated in this analysis, highlighting progressive annual increases in the number of T cell exhaustion-focused publications over the study period. These publications were affiliated with 3117 institutions in 85 countries, with the USA and China being the largest contributors to the field. Of the 18,032 authors associated with these publications, E. John Wherry exhibited the highest publication count and the greatest citation frequency. Keyword analyses indicated that immunotherapy, T cell exhaustion, and PD-1 are the dominant foci for T cell exhaustion-related research. CONCLUSION: These findings highlight the importance of collaborations among institutions and nations in order to further propel novel studies of T cell exhaustion. Efforts to unravel the signal transduction and transcriptional mechanisms underlying the onset of T cell exhaustion were also identified as an emerging hotspot in this field. Ultimately, these results support the pivotal status of T cell exhaustion research as a key direction for immunotherapeutic research and development efforts in the coming years.