TY  - JOUR
A1  - Raoul, William
A1  - Poupel, Lucie
A1  - Tregouet, David-Alexandre
A1  - Lavalette, Sophie
A1  - Camelo, Serge
A1  - Keller, Nicole
A1  - Krumeich, Sophie
A1  - Calippe, Bertrand
A1  - Guillonneau, Xavier
A1  - Behar-Cohen, Francine
A1  - Cohen, Salomon-Yves
A1  - Baatz, Holger
A1  - Combadière, Christophe
A1  - Théry, Clotilde
A1  - Sennlaub, Florian
T1  - MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo
T2  - PLoS One
N2  - Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice.

Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV.

Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls.

Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24344
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-243448
SN  - 1932-6203
VL  - 7
IS  - 3: e33244
PB  - PLoS
CY  - Lawrence, Kan.
ER  -