Abstract
PurposeMilk 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.MethodsThe 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.Resultsrs1878326 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.ConclusionsDespite 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.
Highlights
Milk fat globule-EGF-factor (MFGE8), named lactadherin, PAS 6/7, SED1, BA46, p47, is a secreted glycoprotein first described in milk fat globules released in milk by mammary epithelial cells [1,2]
We investigated whether a single nucleotide polymorphisms (SNP) associated with increased prevalence of lupus in human patients [7] is associated with Age-related Macular Degeneration (AMD)
We investigated whether the deficiency of MFGE8 affects chorioretinal homeostasis and choroidal neovascularization (CNV) in vivo using Mfge82/2 mice
Summary
Milk fat globule-EGF-factor (MFGE8), named lactadherin, PAS 6/7, SED1, BA46, p47, is a secreted glycoprotein first described in milk fat globules released in milk by mammary epithelial cells [1,2]. Secreted by different cell types, it promotes phagocytosis by linking phosphatidylserine at the surface of membrane vesicles [3] and apoptotic cells [4] to the avb3/b5 integrin on phagocytic cells. MFGE8 mediated phagocytosis induces a regulatory T cell response [5] and Mfge82/2 mice develop spontaneous late onset lupus-like disease and glomerulonephritis [6]. MFGE8 binds to avb3/b5 of vascular endothelial cells and promotes VEGF-driven neovascularization [8]. Phagocytosis of spent outer segments (OS) is critical for the long-term maintenance of the retina [9,10] and dependent upon a tyrosine kinase receptor (Mertk) [11,12] and the avb integrin [13].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
