Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Ophthalmology, Emory University, Atlanta, GA, USA.
Clin Exp Pharmacol Physiol. 2020 Jun;47(6):966-976. doi: 10.1111/1440-1681.13284. Epub 2020 Mar 3.
Tumour necrosis factor ligand related molecule 1 A (TL1A), a member of tumour necrosis factor superfamily, has been identified as a crucial regulator for vascular homeostasis and inflammation. However, the function of TL1A in diabetic retinopathy (DR) is largely unknown. This study aims to examine levels of TL1A in serum and intraocular fluid in patients with proliferative diabetic retinopathy (PDR), and to explore the correlation of intraocular TL1A with the prognosis of PDR progression after primary vitrectomy. Seventy-five patients (75 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 19 patients (19 eyes) who received vitrectomy for idiopathic macular holes (IMH) as non-diabetic control group were enrolled in this prospective study. Serum, aqueous and vitreous fluid samples were collected during cataract and PPV surgery. Protein expressions of TL1A as well as other angiogenic and inflammatory cytokines in serum and intraocular fluid were measured. Correlations of intraocular TL1A concentrations with inflammatory cytokines were analyzed. We found both aqueous and vitreous TL1A levels were significantly higher in the PDR group than in control group (P = 0.026; P <0.001). Angiogenic and inflammatory cytokines such as VEGF, IL-6, IL-8, MCP-1, MIP-1α, and MIP-1β were significantly higher in intraocular fluid in PDR group than in controls, which MCP-1 and MIP-1α showed positive correlation with intraocular TL1A levels. There is no significant difference in the levels of serum TL1A as well as other inflammatory cytokines between PDR patients and controls. Intraocular levels of TL1A were significantly lower in PDR progression group than in the stable group (P <0.001; P <0.001). Multivariate logistic regression analyses revealed that lower levels of intraocular TL1A was an important risk factor for predicting PDR progression after primary PPV (OR = 0.717, P = 0.001; OR = 0.684; P = 0.002). In conclusion, TL1A and multiple inflammatory cytokines were highly enriched in the intraocular fluid of PDR patients compared with the controls. Lower levels of intraocular TL1A were associated with development of PDR complications after primary PPV and might be used as prognostic factor in predicting the vitrectomy outcome in PDR patients.
肿瘤坏死因子配体相关分子 1A（TL1A）是肿瘤坏死因子超家族的成员，已被确定为血管稳态和炎症的重要调节剂。然而，TL1A 在糖尿病性视网膜病变（DR）中的功能在很大程度上尚不清楚。本研究旨在检测增生性糖尿病性视网膜病变（PDR）患者血清和眼内液中 TL1A 的水平，并探讨眼内 TL1A 与原发性玻璃体切割术后 PDR 进展预后的相关性。这项前瞻性研究纳入了 75 例（75 只眼）接受经睫状体平坦部玻璃体切除术（PPV）的 PDR 患者和 19 例（19 只眼）接受特发性黄斑裂孔（IMH）玻璃体切除术的非糖尿病对照组患者。在白内障和 PPV 手术期间收集血清、房水和玻璃体液样本。测量血清和眼内液中 TL1A 以及其他血管生成和炎症细胞因子的蛋白表达。分析眼内 TL1A 浓度与炎症细胞因子的相关性。我们发现 PDR 组的房水和玻璃体 TL1A 水平均明显高于对照组（P ＝ 0.026；P ＜0.001）。PDR 组眼内液中的血管生成和炎症细胞因子如 VEGF、IL-6、IL-8、MCP-1、MIP-1α 和 MIP-1β 明显高于对照组，其中 MCP-1 和 MIP-1α 与眼内 TL1A 水平呈正相关。PDR 患者和对照组之间血清 TL1A 水平以及其他炎症细胞因子无显著差异。原发性 PPV 后 PDR 进展组的眼内 TL1A 水平明显低于稳定组（P ＜0.001；P ＜0.001）。多变量逻辑回归分析显示，眼内 TL1A 水平较低是原发性 PPV 后 PDR 进展的重要危险因素（OR ＝ 0.717，P ＝ 0.001；OR ＝ 0.684；P ＝ 0.002）。总之，与对照组相比，PDR 患者的眼内液中 TL1A 和多种炎症细胞因子高度富集。较低的眼内 TL1A 水平与原发性 PPV 后 PDR 并发症的发生有关，可作为预测 PDR 患者玻璃体切割术预后的预后因素。
