Department of Cornea and Refractive Surgery, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Transplantation. 2024 Oct 1;108(10):2072-2083. doi: 10.1097/TP.0000000000005032. Epub 2024 Sep 24.
Immunological rejection is the most common reason for corneal transplantation failure. The importance of T cells in corneal allograft rejection is well demonstrated. Recent studies highlight that pigment epithelium-derived factor (PEDF) plays an immunoregulatory role in ocular diseases by enhancing the suppressive phenotype of regulatory T cells besides its other functions in neurotrophy and antiangiogenesis.
The effects of PEDF on immune rejection were examined in rat models of corneal transplantation using slit-lamp microscope observation, immunohistochemistry, flow cytometry, and Western blot. In vitro, we demonstrated PEDF reduced alloreactive T-cell activation using real-time polymerase chain reaction, flow cytometry, and Western blot.
Topical administration of PEDF provided corneal transplantation rats with an improved graft survival rate of corneal allografts, reduced hemangiogenesis, and infiltration of immune cells in corneas, in particular, type 17 T helper cells while increased regulatory T cells. Moreover, nerve reinnervation within grafts was promoted in PEDF-treated recipient rats. In vitro, PEDF inhibited alloreactive T-cell activation via the c-Jun N-terminal kinase/c-Jun signaling pathway and upregulated the expressions of interleukin-10 and transforming growth factor-β, emphasizing the suppressive role of PEDF on immune responses.
Our results underscore the feasibility of PEDF in alleviating corneal allograft rejection and further illustrate its potential in managing immune-related diseases.
免疫排斥是角膜移植失败的最常见原因。T 细胞在角膜同种异体移植排斥反应中的重要性已得到充分证明。最近的研究强调，色素上皮衍生因子（PEDF）除了在神经营养和抗血管生成方面的其他功能外，通过增强调节性 T 细胞的抑制表型，在眼部疾病中发挥免疫调节作用。
使用裂隙灯显微镜观察、免疫组织化学、流式细胞术和 Western blot 检查 PEDF 对大鼠角膜移植免疫排斥反应的影响。在体外，我们通过实时聚合酶链反应、流式细胞术和 Western blot 证明 PEDF 可减少同种反应性 T 细胞的活化。
局部给予 PEDF 可提高角膜移植大鼠角膜同种异体移植物的存活率，减少血管生成和角膜中免疫细胞的浸润，特别是 1 型 7 辅助性 T 细胞，同时增加调节性 T 细胞。此外，接受 PEDF 治疗的受体大鼠中的神经再支配在移植物中得到促进。在体外，PEDF 通过 c-Jun N 末端激酶/c-Jun 信号通路抑制同种反应性 T 细胞的活化，并上调白细胞介素 10 和转化生长因子-β的表达，强调了 PEDF 对免疫反应的抑制作用。
我们的结果强调了 PEDF 缓解角膜同种异体移植排斥反应的可行性，并进一步说明了其在管理免疫相关疾病方面的潜力。
