Intermediate filament proteins are a heterogeneous group of proteins that form 10-nm-diameter filaments, a highly stable cytoskeletal component occurring in various cell types. The up-regulation of one of these intermediate filament proteins, glial fibrillary acidic protein (GFAP), historically has been an indicator of "stress" in central nervous system (CNS) astrocytes. The retina also responds similarly to "stress" but the up-regulation of intermediate filaments occurs primarily in the Müller cells, the radial glia of the retina. This is a remarkably ubiquitous response in that a similar up-regulation can be observed in numerous forms of retinal degeneration. As a consequence of retinal detachment, a "mechanical" injury to the retina, GFAP, and another intermediate filament protein, vimentin, dramatically increase in Müller cells. Concomitant with this up-regulation is the hypertrophy of these cells both within the retina and onto the photoreceptor and vitreal surfaces of the retina. The function of this distinctive intermediate filament up-regulation in glial cells is unknown, but in the retina their expression is differentially regulated in a polarized manner as the Müller cells hypertrophy, suggesting that they play some role in this process. Moreover the response of intermediate filaments and the Müller cells differs depending on whether the retina has been detached or reattached to the retinal pigment epithelium. The differential expression of these proteins may give insight into their role in the formation of glial scars in the retina and elsewhere in the CNS.