Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr., Salt Lake City, UT 84132, USA.
BMC Neurosci. 2011 Oct 10;12:98. doi: 10.1186/1471-2202-12-98.
The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS) and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b) in the adult mouse and determined the outcome on retinal structure and function.
p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal.
The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.
哺乳动物神经胶质细胞对慢性变性和创伤的反应，被假设为与中枢神经系统（CNS）和视网膜中神经元功能的支持不兼容。为了验证这一假说，我们通过基因敲除成年小鼠中的周期蛋白依赖性激酶抑制剂 p27Kip1（p27 或 Cdkn1b），在没有变性刺激的情况下，开发了一种增殖性反应性神经胶质增生的诱导模型，并确定了其对视网膜结构和功能的影响。
p27 缺陷型 Müller 胶质细胞重新进入细胞周期，经历了异常的迁移，并增强了中间丝蛋白的表达，所有这些都是反应性 Müller 胶质细胞的特征。令人惊讶的是，神经胶质相互作用、视网膜电生理学和视力正常。
增殖性反应性 Müller 胶质增生的良性结果表明，反应性胶质细胞表现出依赖于上下文的、分级的和动态的表型，而且反应本身不一定对神经元功能有害。
