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Editors Selection IGR 9-3

Retinal ganglion cells: Glial stress in glaucoma model

Comment by John Danias on:

19319 Reactive nonproliferative gliosis predominates in a chronic mouse model of glaucoma, Inman DM; Horner PJ, GLIA, 2007; 55: 942-953

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The paper by Inman and Horner (901) investigates whether glaucomatous pathology in the DBA/2 mouse involves glial activation and proliferation. The authors measured the amounts of glial fibrilar acidic protein (GFAP) in the retina of DBA/2 and C57BL/6 mice and correlated it to the average IOP. To detect proliferating cells they gave the animals Bromo-deoxyuridine (BrdU) over consecutive days under two different protocols. They determined the cells that incorporate BrdU by using cell specific markers and measured the numbers of microglial cells that incorporate BrdU in four- and ten-month old DBA/2 mice. GFAP expression at both the mRNA and protein levels increased in DBA/2 mice with age in contrast to C57BL/6 mice where it remained stable. GFAP immunoreactivity localized to Muller cells and astrocytes and correlated with average IOP. Numbers of Muller cells remained stable in DBA/2 mice as determined by counting in retinal sections. A small number of cells in the retina incorporated BrdU in both DBA/2 and C57BL/6 mice (more cells in DBA/2 mice) and the number tended to increase from four to ten months of age. Of these cells a large percentage expressed microglial markers. However, up to 50% of the cells detected did not express any of the markers used and thus were considered immature cells. The authors conclude that microglia proliferated at a fairly slow rate as the disease progressed in DBA/2 mice and thus given the steady numbers of Muller cells there appears to be no significant proliferative gliosis in this model of glaucoma. This is a very important paper as it confirms that in the DBA/2 mouse model of glaucoma GFAP is upregulated indicating glial stress.

In the DBA/2 mouse model of glaucoma GFAP is upregulated indicating glial stress

This upregulation is correlated to IOP even though its start may slightly precede IOP elevation. GFAP increase is not caused by Muller cell or astrocytic proliferation, confirming the absence of major proliferative gliosis within the retina. The fact that any BrdU-positive cells are detected in the retina of both normal and glaucomatous adult animals is astonishing. Even though the numbers are small they seem to increase with age. The fact that differences did not reach statistical significance is probably related to the very low numbers of BrdU positive cells per section. Microglia constitute a large percentage of these cells (~25%) but that is not very surprising. BrdU staining declined with time from administration indicting possible toxicity at the doses used, so it is possible that some of the microglia stained may have ingested BrdU from dying cells. Although none of the BrdU-positive cells in DBA/2 mice expressed the mature neuronal marker used (NeuN), the presence of larger numbers of proliferating cells in this strain compared to the C57BL/6 mice may indicate an unsuccessful attempt at damage repair within the retina.

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