Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Cells. 2023 Jul 21;12(14):1902. doi: 10.3390/cells12141902.
The development of choroidal neovascularization (CNV) is a crucial factor in the pathophysiology and prognosis of exudative age-related macular degeneration (AMD). Therefore, the detection of CNV is essential for establishing an appropriate diagnosis and treatment plan. Current ophthalmic imaging techniques, such as fundus fluorescent angiography and optical coherence tomography, have limitations in accurately visualizing CNV lesions and expressing CNV activity, owing to issues such as excessive dye leakage with pooling and the inability to provide functional information. Here, using the arginine-glycine-aspartic acid (RGD) peptide's affinity for integrin αβ, which is expressed in the neovascular endothelial cells in ocular tissues, we propose the use of fluorescein isothiocyanate (FITC)-labeled RGD peptide as a novel dye for effective molecular imaging of CNV. FITC-labeled RGD peptides (FITC-RGD), prepared by bioconjugation of one FITC molecule with two RGD peptides, demonstrated better visualization and precise localization of CNV lesions than conventional fluorescein dyes in laser-induced CNV rodent models, as assessed using various imaging techniques, including a commercially available clinical fundus camera (Optos). These results suggest that FITC-RGD can serve as an effective novel dye for the diagnosis of neovascular retinal diseases, including AMD, by enabling early detection and treatment of disease occurrence and recurrence after treatment.
脉络膜新生血管（CNV）的发展是渗出性年龄相关性黄斑变性（AMD）病理生理学和预后的关键因素。因此，检测 CNV 对于建立适当的诊断和治疗计划至关重要。目前的眼科成像技术，如眼底荧光血管造影和光相干断层扫描，由于染料过度泄漏和积聚以及无法提供功能信息等问题，在准确可视化 CNV 病变和表达 CNV 活性方面存在局限性。在这里，我们利用 Arg-Gly-Asp（RGD）肽与整合素 αβ的亲和力，该整合素在眼组织中的新生血管内皮细胞中表达，提出使用荧光素异硫氰酸酯（FITC）标记的 RGD 肽作为一种新型染料，用于有效进行 CNV 的分子成像。通过将一个 FITC 分子与两个 RGD 肽进行生物共轭制备的 FITC 标记的 RGD 肽（FITC-RGD），在激光诱导的 CNV 啮齿动物模型中，与传统的荧光染料相比，表现出更好的可视化和更精确的 CNV 病变定位，这通过各种成像技术评估，包括市售的临床眼底相机（Optos）。这些结果表明，FITC-RGD 可以作为一种有效的新型染料，用于诊断新生血管性视网膜疾病，包括 AMD，通过早期检测和治疗疾病的发生和治疗后的复发。
