Reactive nonproliferative gliosis predominates in a chronic mouse model of glaucoma

DM Inman, PJ Horner - Glia, 2007 - Wiley Online Library
Glia, 2007Wiley Online Library
In many CNS diseases, proliferation becomes dysregulated; cells divide and participate in
pathological processes. Gliosis is a fundamental CNS response to trauma or disease in
which cell hypertrophy and proliferation play prominent roles. The DBA/2J mouse is a
glaucoma model in which mice experience gliosis concomitant with raised intraocular
pressure that leads to a slow and progressive retinal ganglion cell axonopathy. We sought to
determine if glaucomatous changes in DBA/2 retina would alter the regulation of cell …
Abstract
In many CNS diseases, proliferation becomes dysregulated; cells divide and participate in pathological processes. Gliosis is a fundamental CNS response to trauma or disease in which cell hypertrophy and proliferation play prominent roles. The DBA/2J mouse is a glaucoma model in which mice experience gliosis concomitant with raised intraocular pressure that leads to a slow and progressive retinal ganglion cell axonopathy. We sought to determine if glaucomatous changes in DBA/2 retina would alter the regulation of cell proliferation, specifically in relation to retinal glia. Astrocyte and Müller glia populations within DBA/2 retina upregulated glial fibrillary acidic protein mRNA and protein compared with C57Bl/6; microglial cell number increased twofold from 4 to 10 months. Various bromodeoxyuridine (BrdU) injection paradigms were used to label dividing cells in DBA/2 and C57Bl/6 retina at 4 and 10 months of age. Very modest cell division in the retina, primarily in ganglion cell and inner nuclear layers, was observed at all ages. Immunohistochemistry indicated cell turnover primarily of NG21 pericytes and Iba11 microglia; astrocytes and Müller glia did not proliferate. There were no significant differences in BrdU1 cell numbers in 4 and 10-month-old retina, though 4-month retina had generally fewer BrdU1 cells than 10-month. C57Bl/6 retinas had fewer BrdU1 cells than DBA/2 retinas at all ages. These data show that, in contrast to gliosis in other CNS trauma and neurodegenerative diseases, glaucomatous changes in retina do not include substantive cell proliferation. Retinal changes in a chronic model of glaucoma engender a reactive, not proliferative, gliosis response. VC 2007 Wiley-Liss, Inc.
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