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Donita Garland, John D. Lambris, Eric A. Pierce; The Complement System Contributes to Basal Laminar Deposit Formation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):959.
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Several lines of evidence implicate the complement system in age-related macular degeneration (AMD), however, the underlying mechanisms are not understood. The purpose of this study was to determine if complement plays a role in the formation of basal laminar deposits, an early step in the development of AMD.
Efemp1-R345W knockin mice were used for this study as they develop sub-RPE basal laminar deposits with age that are similar to those observed in AMD. The knockin mice were crossed with complement C3 null mice because in the absence of C3 the complement system is non-functional. Homozygous double mutant mice were generated. At 14 months of age retinal sections were prepared for transmission electron microscopy using standard techniques for the double mutant mice, Efemp1-R345W mice, and C3 null and wild type control mice. Images of Bruch’s membrane and the RPE were acquired every 25 microns from the optic nerve to the retinal periphery. The images were each scored for the total area of basal deposits using ImageJ software. Statistical significance was determined using the Student’s t-test.
The formation of basal laminar deposits was significantly decreased in the homozygous Efemp1-R345W: C3 null double mutant mice relative to that in Efemp1-R345W knockin mice (> 90% confidence level). The level of basal deposits in the double mutant mice was comparable to that in the C3 null and wild type control mice. Disrupted basal infoldings and RPE vacuoles were still present in the double mutant mice suggesting that complement was primarily involved in basal deposit formation.
The results of this study strongly support a role for the complement system in the formation of basal laminar deposits in the Efemp1-R345W knockin mice. We speculate that complement also has an important role in basal laminar deposit formation in individuals at risk for age-related macular degeneration.
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