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Hideo Kohno, Yu Chen, Tadao Maeda, Krzysztof Palczewski, Akiko Maeda; Subretinal Microglia/Macrophages Contribute To Retinal Degeneration Caused by All-trans-retinal. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3359.
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To investigate the role of retinal inflammation in all-trans-retinal-associated retinal degeneration, we examined subretinal translocation of retinal microglia, which are tissue resident macrophages in the retina, and macrophages, which are supplied from the retinal circulation into the inner retina.
Rdh8-/-Abca4-/- mice, which show impaired metabolism of all-trans-retinal, and WT mice at 4 weeks of age were exposed to light at 10,000 lux for 30 min. Retinal phenotypes of these mice were assessed by in vivo imaging techniques, such as Scanning Laser Ophthalmoscopy (SLO) and Optical Coherence Tomography (OCT), and histological analyses.Clodronate-liposomes, which can deplete macrophages, were injected into Rdh8-/-Abca4-/- mice immediately after light via tail vein to examine the role of macrophages in light-induced retinal degeneration. To determine possible triggers for translocation of microglia/macrophages to the subretinal space, we measured mRNA expression of those molecules in Rdh8-/-Abca4-/- and WT mice 24 h and 7days after light exposure.
Light-exposed Rdh8-/-Abca4-/- mice showed a significant accumulation of autofluorescent spots in the subretinal space, whereas WT mice did not display such changes. This accumulation started 3 days after light and peaked at 7 days. Flat-mount RPE of light exposedRdh8-/-Abca4-/- eyes showed Iba-1-, a marker of activated macrophage and microglia, and F4/80- , a marker of macrophages, positive cells in the apical side of the RPE. The administration of Clodronate-liposomes reduced the numbers of autofluorescent spots in light exposed Rdh8-/-Abca4-/- mice, which showed milder retinal degeneration and weaker activation of microglial and Muller glial cells. RNA analyses revealed increased expression of several molecules, including Ccl2, Ccr2, Tnf and Il1b in retinas of light exposed Rdh8-/-Abca4-/- mice.
Accumulation of microglia/macrophages in the subretinal space contributes to retinal degeneration in mice with delayed clearance of all-trans-retinal. Increased expression of various chemokines and cytokines after light exposure in Rdh8-/-Abca4-/- mice is a possible mechanism for the subretinal accumulation of these cells
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