Purchase this article with an account.
Nan-Kai Wang, Chi-Chun Lai, Chi-Hsiu Liu, Lung-Kun Yeh, Takayuki Nagasaki, Stephen Tsang; The Role of Microglia in Retinal Degeneration of Mice with Defective NR2E3 Gene. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1375.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of microglia in rd7/rd7 mice, which are a mouse model of enhanced S-cone syndrome (ESCS)
rd7/rd7 mice were outcrossed to Mafia (Tg/Tg) mice. The two-generation outcross-intercross series was used to generate rd7/rd7;Tg/Tg double homozygous for Nr2e3 rd7/rd7 mutation and Tg/Tg. Offspring from an incross of rd7/rd7;Tg/Tg mice were used in this study. AP20187 was used to systemic ablation of bone marrow-derived microglia in rd7/rd7;Tg/Tg mice. Immunohistochemical analysis, flow cytometry, electron microscopy, and western blot were used in this study.
Sequential analyses of retinal rosettes and AF spots revealed that retinal rosettes appeared earlier than AF spots, suggesting that microglia are recruited and appear after the formation of the outer nuclear layer folding. We demonstrated that the majority of microglial cells present in the retina of rd7/rd7;Tg/Tg mice expressed green fluorescence protein. After systemic depletion of circulating bone marrow (BM)-derived microglia, the cilioretinal flatmount in rd7/rd7;Tg/Tg mice showed characteristics that mimic those of later stages of retinal degeneration in rd7 mice. Further analyses of the outer nuclear layer confirmed a decrease in the number of nuclei in rd7/rd7;Tg/Tg mice injected with AP20187. Photoreceptor loss after systemic depletion of circulating BM-derived cells may be associated with the upregulation of cytotoxic molecules, such as TNF-a and IL-1B.
These resident microglia established a cytokine milieu that skewed to inflammation, which subsequently accelerated retinal degeneration. Future studies dedicated to the search for therapeutic agents to intervene in the inflammatory processes involved in retinal degeneration should investigate the molecular signals that act between microglial activation and photoreceptor loss.
This PDF is available to Subscribers Only