Cell-Type-Specific Complement Profiling in the ABCA4 -/- Mouse Model of Stargardt Disease

Stargardt macular degeneration is an inherited retinal disease caused by mutations in the ATP-binding cassette subfamily A member 4 (ABCA4) gene. Here, we characterized the complement expression profile in ABCA4 retinae and aligned these findings with morphological markers of retinal degeneration. W...

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Veröffentlicht in:International journal of molecular sciences 2020-11, Vol.21 (22), p.8468
Hauptverfasser: Jabri, Yassin, Biber, Josef, Diaz-Lezama, Nundehui, Grosche, Antje, Pauly, Diana
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creator Jabri, Yassin
Biber, Josef
Diaz-Lezama, Nundehui
Grosche, Antje
Pauly, Diana
description Stargardt macular degeneration is an inherited retinal disease caused by mutations in the ATP-binding cassette subfamily A member 4 (ABCA4) gene. Here, we characterized the complement expression profile in ABCA4 retinae and aligned these findings with morphological markers of retinal degeneration. We found an enhanced retinal pigment epithelium (RPE) autofluorescence, cell loss in the inner retina of ABCA4 mice and demonstrated age-related differences in complement expression in various retinal cell types irrespective of the genotype. However, 24-week-old ABCA4 mice expressed more in the RPE and fewer transcripts in the microglia compared to controls. At the protein level, the decrease of complement inhibitors (complement factor I, CFI) in retinae, as well as an increased C3b/C3 ratio in the RPE/choroid and retinae of ABCA4 , mice was confirmed. We showed a corresponding increase of the C3d/C3 ratio in the serum of ABCA4 mice, while no changes were observed for CFI. Our findings suggest an overactive complement cascade in the ABCA4 retinae that possibly contributes to pathological alterations, including microglial activation and neurodegeneration. Overall, this underpins the importance of well-balanced complement homeostasis to maintain retinal integrity.
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subjects Age
Aging
Albinism
Animals
ATP-Binding Cassette Transporters - metabolism
Choroid - metabolism
Complement
Complement activation
Complement Activation - physiology
Complement component C3
Complement component C3b
Complement factor I
Complement inhibitors
Complement System Proteins - metabolism
Diabetic retinopathy
Disease
Disease Models, Animal
Epithelium
Female
Gene expression
Genotype & phenotype
Genotypes
Homeostasis
Macular degeneration
Macular Degeneration - metabolism
Male
Mice
Mice, Inbred BALB C
Microglia
Microglia - metabolism
Mutation
Neurodegeneration
Oxidative stress
Photoreceptors
Ratios
Retina
Retina - metabolism
Retinal cells
Retinal degeneration
Retinal Degeneration - metabolism
Retinal pigment epithelium
Retinal Pigment Epithelium - metabolism
Stargardt Disease - metabolism
title Cell-Type-Specific Complement Profiling in the ABCA4 -/- Mouse Model of Stargardt Disease
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