J Clin Invest：炎症因子或可增加衰老视网膜变性可能

7月16日，J Clin Invest.杂志在线报道高水平的炎症因子和缺乏神经保护性因子可能是与衰老有关的视网膜变性的重要诱因。

由多个基因影响的细胞过程的异常和整个生命进程中各种细胞损伤的积累，决定着与衰老有关的疾病的进展，但其复杂的病因知之甚少。

有丝分裂后神经元，如与视网膜色素上皮相邻的上皮细胞和视网膜感光细胞，特别容易受到细胞衰老的影响，这可促进与衰老有关的视网膜变性（ARD）。

ARD的病因复杂，缺乏有效的化合物进行早期预防和治疗。为了解驱动ARD的发病机制，科学家研究了ARD发病率明显高于其他近交系小鼠的A / J小鼠。

虽然对小鼠品系染色体的研究，未能确定与所观察到的视网膜老化相关的染色体，但是，对视网膜病理改变前的年轻小鼠RNA序列数据的分析显示，在A/ J小鼠易发生ARD是由于它们具有高水平炎性细胞因子和低水平的神经保护性因子。

本研究所揭示的ARD进展相关的炎性状态特征，有助于人们了解许多衰老相关疾病的致病机制，其中包括一些人类致盲疾病。

doi:10.1016/j.cell.2011.10.017
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Inflammatory priming predisposes mice to age-related retinal degeneration

Debarshi Mustafi1, Tadao Maeda1,2, Hideo Kohno1, Joseph H. Nadeau3 and Krzysztof Palczewski

Disruption of cellular processes affected by multiple genes and accumulation of numerous insults throughout life dictate the progression of age-related disorders, but their complex etiology is poorly understood. Postmitotic neurons, such as photoreceptor cells in the retina and epithelial cells in the adjacent retinal pigmented epithelium, are especially susceptible to cellular senescence, which contributes to age-related retinal degeneration (ARD). The multigenic and complex etiology of ARD in humans is reflected by the relative paucity of effective compounds for its early prevention and treatment. To understand the genetic differences that drive ARD pathogenesis, we studied A/J mice, which develop ARD more pronounced than that in other inbred mouse models. Although our investigation of consomic strains failed to identify a chromosome associated with the observed retinal deterioration, pathway analysis of RNA-Seq data from young mice prior to retinal pathological changes revealed that increased vulnerability to ARD in A/J mice was due to initially high levels of inflammatory factors and low levels of homeostatic neuroprotective factors. The genetic signatures of an uncompensated preinflammatory state and ARD progression identified here aid in understanding the susceptible genetic loci that underlie pathogenic mechanisms of age-associated disorders, including several human blinding diseases.