Purchase this article with an account.
M. P. Krebs, H. Ko, R. T. Tzekov, E. W. Scott, S. Kaushal; Circles of RPE Nuclei and Regional Dystrophy of the Retina and RPE Correlate with Microglial Activation in Ccl2/Cx3cr1 Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6167.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To explore the hypothesis that defects in microglial mobilization and activation within the eye can cause age-related macular degeneration (AMD).
Regional damage was first demonstrated by fundoscopy of young DKO mice, which revealed white spots only in the inferior temporal quadrant of the eye. The spots were correlated with localized displacement of the outer nuclear layer toward the RPE, appearing as bumps in nuclear-stained retinal flat mounts and outer nuclear layer folds in cryosections. CD11b+ microglia were mislocalized to these bumps, which showed an increased number of TUNEL+ photoreceptor nuclei suggesting microglial activation. An unusual morphological feature was also observed in the RPE inferior temporal quadrant, where nuclei of cells surrounding a central cell were closely apposed in a circle bordering the central cell. Subretinal CD11b+ microglia were often associated with this feature, which may be a prelude to regional RPE dystrophy. In older animals, white spots distributed throughout the posterior pole and non-leaking lesions in the inferior temporal quadrant were detected by fundoscopy. These lesions were characterized by dystrophic changes in the retina and underlying RPE.
Mislocalized, activated retinal microglia in DKO mice are associated with an unusual circular positioning of RPE nuclei and with regional dystrophy of the retina and RPE. These results are consistent with the hypothesis that dysfunctional microglia can cause degenerative changes similar to AMD in humans.
This PDF is available to Subscribers Only