Department of Orbital Diseases, Affiliated Eye Hospital of Nanchang University, Nanchang, China; Department of Orbital Diseases, Eye Hospital of Jiangxi Province, Nanchang, China; Nanchang University School of Ophthalmology & Optometry, Nanchang, China; The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, China; The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Department of Orbital Diseases, Affiliated Eye Hospital of Nanchang University, Nanchang, China; Department of Orbital Diseases, Eye Hospital of Jiangxi Province, Nanchang, China; Nanchang University School of Ophthalmology & Optometry, Nanchang, China; The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, China; Department of Medical Technology, Chongqing Three Gorges Medical College, Chongqing, China.
Gene. 2025 Jan 30;935:149049. doi: 10.1016/j.gene.2024.149049. Epub 2024 Oct 28.
The hydroxyapatite orbital implantation is widely used to treat orbital malformation, but delayed postoperative angiogenesis can hinder conjunctival wound healing, potentially leading to implant exposure and prolapse. Low-intensity laser therapy (LLLT) is recognized for its ability to promote tissue regeneration, reduce inflammation, and alleviate pain. This study aims to explore the specific mechanism of miRNAs-VEGFA pathway regulation in early vascularization after orbital implant placement induced by LLLT. A hydroxyapatite orbital implant model was established and treated with LLLT. Vascular tissues surrounding the ocular prosthesis were extracted for high-throughput sequencing to identify differentially expressed miRNAs. miRNAs predicted to bind with VEGFA were selected for validation. GO and KEGG analyses were performed to reveal the functional enrichment of target genes regulated by these miRNAs. Dual luciferase assay, qRT-PCR, and Western blotting were used to verify the targeting relationship between miR-90 and VEGFA. The effects of miR-90 on rabbit microvascular endothelial cell function were assessed through CCK-8 assay, scratch test, and tube formation assay. High-throughput sequencing revealed 32 differentially expressed miRNAs, with 8 upregulated and 24 downregulated. miR-90 was predicted to have a high binding score and expression abundance with VEGFA and was confirmed to regulate VEGFA expression. In vitro functional tests showed that miR-90 inhibited rabbit microvascular endothelial cell proliferation, migration, and tube formation. This study is the first to demonstrate that LLLT regulates ocular prosthesis angiogenesis via the miR-90/VEGFA pathway, providing a new target for treating vascular-dependent diseases.
羟基磷灰石眶内植入物广泛用于治疗眼眶畸形，但术后迟发性血管生成可阻碍结膜伤口愈合，可能导致植入物暴露和脱出。低强度激光疗法（LLLT）已被公认为可促进组织再生、减轻炎症和缓解疼痛。本研究旨在探讨 LLLT 诱导眶内植入物放置后早期血管化中 miRNAs-VEGFA 通路调节的具体机制。建立了羟基磷灰石眶内植入物模型，并进行 LLLT 治疗。提取眼部假体周围的血管组织进行高通量测序，以鉴定差异表达的 miRNAs。选择预测与 VEGFA 结合的 miRNAs 进行验证。进行 GO 和 KEGG 分析以揭示受这些 miRNAs 调控的靶基因的功能富集。双荧光素酶报告基因检测、qRT-PCR 和 Western blot 用于验证 miR-90 与 VEGFA 之间的靶向关系。通过 CCK-8 测定、划痕试验和管形成试验评估 miR-90 对兔微血管内皮细胞功能的影响。高通量测序显示 32 个差异表达的 miRNAs，其中 8 个上调，24 个下调。miR-90 与 VEGFA 具有高结合评分和表达丰度，被预测为调节 VEGFA 表达。体外功能测试表明 miR-90 抑制兔微血管内皮细胞增殖、迁移和管形成。本研究首次证明 LLLT 通过 miR-90/VEGFA 通路调节眼部假体血管生成，为治疗血管依赖性疾病提供了新的靶点。
