Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

This paper by Vazquez-Chona FR, Swan A, Ferrell WD, Jiang L, Baehr W, Chien WM, Fero M, Marc RE and Levine EM addresses a long standing issue in the field of neuroscience: is the reactive phenotype of glial cells in and of itself detrimental to neural survival or function?

It is generally assumed that certain modifications in glial behavior such as increased proliferation or upregulation of the intermediate filament protein GFAP contribute to the pathological processes associated with CNS injuries or degeneration.  In cases where cell-intrinsic glial factors were manipulated during the course of injury such as traumatic brain injury, the results have been mixed; in some cases, glial reactivity has a protective role and not in others.  These studies highlight the complexities of glia in neural tissue homeostasis, function and survival as well as the difficulties in separating cause from effect.  What is needed is a way to functionally dissect the intrinsic phenotype of glial reactivity from extrinsic insults.  In this study, the authors accomplished this by generating a genetic murine model that exhibits three classic indices of glial reactivity in the retina—proliferation, intermediate filament upregulation, and migratory-like behavior.  This was accomplished by conditionally inactivating p27Kip1, a cyclin-dependent kinase inhibitor in the adult retina.  Because p27Kip1 is restricted to Müller glia in the adult retina, they assessed its loss of function on Müller glia behavior without inducing injury or degeneration.  The absence of any initial degeneration allowed the unique opportunity to evaluate the intrinsic impact on retinal neuroglial interactions and visual function.  Their data argue that reactivity per se does not impact the ability of the Müller glia to provide homeostatic support to retinal neurons and photoreceptors which supports the argument that the intrinsic properties of reactive glia on their own are not detrimental features of CNS pathologies.