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D. Inman, B.P. Buckingham, R.M. Sappington, D.J. Calkins, P.J. Horner; Retinal Vessel Volume and Pericyte Number Decrease Over Time in the DBA/2 Mouse Model of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1320.
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Purpose: There is a tight relationship between vascular volume/flow and the metabolic and inflammatory state of the CNS. Capillary volume is tightly associated with metabolic demand, increasing with activity and cell proliferation; it becomes dysregulated during inflammatory conditions. Astrocytes and pericytes control the vascular flow and the tightness of the blood–retina barrier. Using the DBA/2 mouse model of glaucoma, in which the mouse develops iris atrophy and pigment dispersion that often leads to increased intraocular pressure and eventual retinal ganglion cell loss, we sought to determine if there is an angiogenic response to disease progression which would indicate increased metabolic demand or an inflammatory response. We also sought to determine if there was evidence of vascular flow dysregulation in response to the glaucoma. Methods: FITC–dextran perfused eyes obtained from DBA/2 and C57Bl/6 mice were fixed, retinas removed and immunolabeled with NG2, a marker of retinal pericytes. Vascular elements and pericytes were counted in 2– to 11–month–old DBA/2 and C57Bl/6 retinal whole mounts using an unbiased stereological approach. Results: DBA/2 retinal vasculature significantly decreased its carrying capacity with age while that of the C57Bl/6 did not change. The DBA/2 mouse had significantly fewer pericytes than age–matched C57Bl/6, and DBA/2 mice lost pericytes with age. The ratio of pericytes to vascular elements was significantly reduced compared to that of C57Bl/6 mice. A loss in the total length of vascular elements in the DBA/2 retina––which reaches significance at 11 months––indicates that a large peripheral immune response is absent but that metabolic activity is decreased, likely due to the documented loss of RGCs. Vasculature in the DBA/2 remained patent, with few localized instances of FITC–dextran leakage beyond the vasculature. Conclusions: Given that pericytes are probably responsible for local control of blood flow and may participate in the activation of antigen presentation and the peripheral immune response, significantly fewer pericytes and decreased vessel volume suggest that the DBA/2 retina is likely less able to react to changes in pressure or metabolic demand and that this is exacerbated as the mice age.
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