INSERM, U968, Paris, France.
PLoS One. 2011;6(12):e28791. doi: 10.1371/journal.pone.0028791. Epub 2011 Dec 9.
Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome.
METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here.
CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.
视网膜脱离常导致严重且永久性的视力丧失，其治疗管理至今仍完全依赖于手术。我们使用手术标本对脱离后人类视网膜组织的转录组进行差异分析，以鉴定新的潜在药理靶点，这些靶点可与手术联合使用，以进一步改善最终结果。
方法/主要发现：统计分析显示，免疫反应在疾病中起主要作用。有趣的是，我们采用一种新的方法，依赖协调表达，监测个体间的变异，以揭示病理过程的另一个关键方面：光感受器细胞的死亡。在所鉴定的基因中，主要组织相容性复合体 I 基因 HLA-C 的表达可用于疾病的诊断，而 PKD2L1 和 SLCO4A1 的表达下调则协同作用，提供视网膜脱离过程持续时间的估计。因此，我们的分析揭示了与视网膜脱离相关的两个互补的细胞和分子方面：免疫反应和光感受器细胞的变性。我们还发现，与未参与本研究中手术标本的人工模型相比，人类标本具有更高的临床价值，这些人工模型指出 IL6 和氧化应激与视网膜脱离有关。
结论/意义：这项系统分析证实了在视网膜脱离过程中同时发生神经退行性变和炎症，并且进一步精确地确定了参与这两种现象的不同基因表达的改变。我们的数据为治疗策略提供了新的见解，这些策略旨在限制与视网膜脱离相关的炎症和光感受器损伤，从而改善视网膜手术后的视觉预后。
