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Jessica Hines-Beard, Aaron C Suggs, Tonia S Rex; Early and Age-Related Changes in the Glaucomatous DBA/2J Retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2405.
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Our goal is to characterize age-related glaucomatous disease progression in the DBA/2J.
Intraocular pressure (IOP) was measured at 3 months and then every other week from 5-8 months of age to verify glaucoma. Visual evoked potentials (VEP) were performed at 3, 6, 8, and 10 months. Retinas were agarose embedded, and 70-micron-thick retina cross-sections were immunostained with C1q and PSD95 or with Iba-1 and imaged by confocal microscopy.
Baseline IOP measurements were 14mmHg; therefore, eyes with IOP of at least 17mmHg at 6 months of age were used in this study. The VEP N1 and P1 amplitudes decreased significantly over time. Reactive microglia were detected in retinas of 6, 8, and 10-month old mice, but not in 3-month olds. Basal levels of C1q labeling were detected in the inner plexiform layer (IPL) of 3-month-old retinas. C1q labeling in the IPL was stronger at 6 months and decreased again at 8 and 10 months of age. Minimal colocalization of C1q and PSD95 was detected at any age.
The VEP amplitude decreased as early as 6 months of age, when axon degeneration begins in this model, indicating that the VEP may be a sensitive measure of glaucomatous degeneration. We confirm the findings of others that microglia are reactive early in glaucoma pathogenesis, and are a therapeutic target. The lack of significant colocalization of C1q with RGC dendrites argues against C1q-mediated dendritic pruning as an early event in glaucoma. The increase in C1q at 6 months could still indicate a role for the classical complement cascade in early glaucoma pathogenesis. We have identified microglia and complement as early markers and therapeutic targets in the DBA/2J model of glaucoma, and we show that VEP can be used as a non-invasive, sensitive indicator of axon degeneration.
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