Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy

ABSTRACT Purpose: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. Methods: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). Results: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. Conclusions: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.

摘要
研究目的：对比增生性糖尿病视网膜病变（proliferative diabetic retinopathy）与其他玻璃体视网膜疾病患者体内参与神经退行性变、炎症及血管生成的细胞介质的玻璃体内浓度。
研究方法：采用多重微球免疫分析法（multiplex bead immunoassay），对接受23G玻璃体切割术的增生性糖尿病视网膜病变患者及其他诊断患者（对照组）的玻璃体样本中以下因子水平进行检测：色素上皮源性因子（pigment epithelium-derived factor）、血清淀粉样蛋白P（serum amyloid P）、C反应蛋白（C-reactive protein）、补体C4（complement C4）、α1-抗胰蛋白酶（alpha-1 antitrypsin）、血管内皮生长因子（vascular endothelial growth factor）、血小板源性生长因子-AA（platelet-derived growth factor-AA）、血小板源性生长因子-BB（platelet-derived growth factor-BB）、白细胞介素-6（interleukin-6）、白细胞介素-8（interleukin-8）、白细胞介素-10（interleukin-10）、肿瘤坏死因子α（tumor necrosis factor alpha）及肿瘤坏死因子β（tumor necrosis factor beta）。
研究结果：本研究共纳入55例患者，其中24例为增生性糖尿病视网膜病变患者，31例为其他诊断患者，包括玻璃体积血、视网膜脱离、黄斑裂孔及视网膜前膜。与对照组相比，增生性糖尿病视网膜病变患者的血清淀粉样蛋白P（85.49 vs. 31.38 ng/mL）、C反应蛋白（59.89 vs. 41.75 ng/mL）、血管内皮生长因子（2330.11 vs. 554.25 pg/mL；p<0.001）、血小板源性生长因子A（127.32 vs. 39.11 pg/mL）、血小板源性生长因子B（29.37 vs. 7.12 pg/mL）、白细胞介素-6（69.37 vs. 33.58 pg/mL）、白细胞介素-8（175.25 vs. 59.71 pg/mL）及白细胞介素-10（3.70 vs. 1.88 pg/mL）水平均显著升高，所有指标组间比较p值均<0.004。而色素上皮源性因子（30.06 vs. 27.48 ng/mL；p=0.295）、补体C4（570.78 vs. 366.24 ng/mL；p=0.069）及α1-抗胰蛋白酶（359.27 vs. 522.44 ng/mL；p=0.264）的组间水平差异无统计学意义。肿瘤坏死因子α及肿瘤坏死因子β的玻璃体内水平未检出。血清淀粉样蛋白P、C反应蛋白、血小板源性生长因子A、血小板源性生长因子B、白细胞介素-6及白细胞介素-8与血管内皮生长因子呈正相关。
研究结论：参与神经退行性变及炎症过程的细胞介质在增生性糖尿病视网膜病变患者的玻璃体液中水平升高，或参与糖尿病视网膜病变的发病机制。