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Sex-dependent amelioration of laser-induced choroidal neovascularization by Short-Chain Fatty Acid treatment in a mouse model

ABSTRACT: Sex-dependent amelioration of laser-induced choroidal neovascularization by Short-Chain Fatty Acid treatment in a mouse model

PROVIDER: PRJNA1276071 | ENA |

REPOSITORIES: ENA

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Sex-dependent amelioration of laser-induced choroidal neovascularization by Short-Chain Fatty Acid treatment in a mouse model

Project description:Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a clinical presentation that varies between sexes. In late-stage AMD, choroidal neovascularization (CNV) triggers retinal inflammation and degeneration, processes that are exacerbated by an overactive response of retinal microglial cells. Short-chain fatty acids (SCFAs) have emerged as potential treatments for AMD due to their anti-inflammatory properties. In this study, we investigate the effects of SCFA treatment in a laser-induced CNV mouse model, focusing on sex-dependent differences in disease progression and microglial response. Our findings demonstrate distinct sex-specific patterns in the development of CNV and associated pathological hallmarks. SCFA treatment resulted in a slight increase in density of Iba1+ microglial cells in females at 3 days post-laser (3dpl), while it prevented a massive increase in males at 7 dpl, with both sexes showing enhanced microglial ramification. The dynamics of microglial density were linked to protective effects on CNV, leakage size, and inflammation, which occurred earlier in females and later in males. In vitro assays revealed that SCFAs reduced microglial phagocytosis of retinal debris, suggesting a potential mechanism for their anti-inflammatory action. This study underscores the importance of considering sex-specific responses in the development of AMD treatments, such as SCFAs, and highlights the need for personalized therapeutic strategies.

2025-07-01 | GSE299691 | GEO

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Project description:To investigate the tRF/tiRNA expression pattern in the development of choroidal neovascularization, we built a laser-induced choroidal neovascularization mouse model and performed the tRF/tiRNA sequencing on RPE-choroid-sclera complexes at different time points after model establishment, while the tissues from mice without treatment were used as control group.

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Proteotranscriptomic Analyses in Laser-Induced Choroidal Neovascularization

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Expression profile of circRNAs in a mouse model of laser-induced choroidal neovascularization

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Expression profiles of long non-coding RNAs and messenger RNAs in laser-induced choroidal neovascularization in mice.

Project description:Choroidal neovascularization (CNV) is a severe complication of the late-stage form of wet age-related macular degeneration. In order to identify lncRNAs and coding genes involved in the pathogenesis of CNV, we performed microarray analysis to identify expression profiles of lncRNAs and mRNAs in laser-induced CNV samples and controls in mice.

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Expression profiles of microRNAs and transfer RNA-derived small RNAs in laser-induced choroidal neovascularization in mice.

Project description:The purpose of the study was to investigate the roles and possible functions of the miRNAs and tsRNAs in choroidal neovascularization (CNV).The mouse model of laser-induced CNV was conducted by laser photocoagulation and the samples were collected 7 days after laser treatment. The expression profiles of miRNAs and tsRNAs were accessed by small RNA sequencing in RPE-choroid-sclera complexes of mice in CNV group and controls. Our study identified differential expressions of miRNAs and tsRNAs in CNV model, and these altered miRNAs and tsRNAs might be novel potential targets in treating CNVs in patients with neovascular age-related macular degeneration.

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Expression profile of circRNAs in a mouse model of laser-induced choroidal neovascularization

Project description:Expression profile of circRNAs in a mouse model of laser-induced choroidal neovascularization

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RNA analysis of the circadian rhythm of choroidal neovascularization

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CD11c+ macrophages are pro-angiogenic and necessary for experimental choroidal neovascularization

Project description:Patients with neovascular AMD (nAMD) suffer vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Macrophages are found in CNV lesions from nAMD patients. Additionally, Ccr2-/- mice, which lack classical monocyte-derived macrophages, show reduced CNV size. However, macrophages are highly diverse cells that can perform multiple functions. We performed single-cell RNA-sequencing on immune cells from wildtype and Ccr2-/- eyes to uncover macrophage heterogeneity during the laser-induced CNV mouse model of nAMD. We identified 12 macrophage subtypes, including Spp1+ macrophages. Spp1+ macrophages were enriched from wildtype lasered eyes and expressed a pro-angiogenic transcriptome via multiple pathways, including vascular endothelial growth factor signaling, endothelial cell sprouting, cytokine signaling, and fibrosis. Additionally, Spp1+ macrophages expressed the marker CD11c, and CD11c+ macrophages were increased by laser and present in CNV lesions. Finally, CD11c+ macrophage depletion reduced CNV size by 40%. These findings broaden our understanding of ocular macrophage heterogeneity and implicate CD11c+ macrophages as a potential therapeutic target for treatment-resistant nAMD patients.

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