OBJECTIVE To evaluate the association of aqueous retinol-binding protein 3 (RBP3) with history of diabetic macular edema (DME) and diabetic retinopathy (DR) progression. RESEARCH DESIGN AND METHODS RBP3 concentration was measured by ELISA in aqueous from patients undergoing cataract surgery at Joslin Diabetes Center. DR progression was defined as two-step or more worsening on the Early Treatment Diabetic Retinopathy Study severity scale, and DME history was determined by clinical diagnosis. RESULTS In 153 eyes (31 with type 1 and 122 with type 2 diabetes; n = 149 patients), 37% had no signs of DR, 40% had mild nonproliferative DR (NPDR), and 23% had moderate NPDR. Aqueous RBP3 decreased from a median of 2.1 nmol/L (interquartile range 0.8–3.4) in eyes with no DR to 1.5 nmol/L (0.8–3.8) in eyes with mild-to-moderate NPDR (P = 0.047). The difference between aqueous RBP3 levels in those with type 1 or type 2 diabetes was not significant. Elevated RBP3 (β = −0.701, 95% CI −1.151 to 0.250, P = 0.002) was associated with no DME history. With a mean follow-up of 5.5 ± 3.6 years, elevated RBP3 at baseline was associated with less subsequent DR progression (odds ratio 0.51, 95% CI 0.28–0.93, P = 0.03). In multivariable analyses, RBP3 remained significantly associated with a DR progression and history of DME. A 5% improvement was seen in the area under the curve when RBP3 was added to clinical models for predicting DR progression (P < 0.05). CONCLUSIONS This study suggests that aqueous RBP3 may be an important protective factor, the first neuroretinal-specific biomarker of DME or DR progression, and a possible therapeutic target.

中文翻译：

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视黄醇结合蛋白 3 浓度降低与糖尿病性黄斑水肿和糖尿病视网膜病变的进展有关


目的 评价水性视黄醇结合蛋白 3 （RBP3） 与糖尿病性黄斑水肿 （DME） 病史和糖尿病视网膜病变 （DR） 进展的关系。研究设计和方法 通过 ELISA 测量 Joslin 糖尿病中心接受白内障手术的患者水中 RBP3 浓度。DR 进展定义为早期治疗糖尿病视网膜病变研究严重程度量表上两级或更多恶化，DME 病史由临床诊断确定。结果 在 153 只眼 （31 只 1 型糖尿病和 122 只 2 型糖尿病患者;n = 149 名患者） 中，37% 没有 DR 迹象，40% 有轻度非增殖性 DR （NPDR），23% 有中度 NPDR。水性 RBP3 从无 DR 眼的中位数 2.1 nmol/L（四分位距 0.8-3.4）下降到轻度至中度 NPDR 眼的 1.5 nmol/L （0.8-3.8） （P = 0.047）。1 型或 2 型糖尿病患者 RBP3 水水平之间的差异不显著。RBP3 升高 （β = -0.701,95% CI -1.151 至 0.250，P = 0.002）与无 DME 病史相关。平均随访 5.5 ± 3.6 年，基线时 RBP3 升高与随后的 DR 进展较少相关 （比值比 0.51,95% CI 0.28-0.93，P = 0.03）。在多变量分析中，RBP3 与 DR 进展和 DME 病史仍显著相关。当 RBP3 添加到预测 DR 进展的临床模型中时，曲线下面积改善了 5% （P < 0.05）。结论 本研究表明，水性 RBP3 可能是一个重要的保护因子，是 DME 或 DR 进展的第一个神经视网膜特异性生物标志物，也是一个可能的治疗靶点。