It has been reported previously that 50% of NMDA receptors are associated to lipid rafts

were evaluated. To investigate if the disruption of ASMase affects the RPE function, we evaluated the ERG c-wave amplitudes and autofluorescence signals. As shown in Fig 4, at 1 month-of-age, the mean c-wave amplitude in ASMase KO mice (213.9 � 26.3 V) was significantly lower than that in WT mice (318.2 � 14.2 V), and amplitudes continued to decline to 120.2 � 26.8 V at 2 months-of- age. All images were taken 2 to 3 disc diameters from the optic nerve. Scale bar is 20 m. Abbreviations: retinal pigment epithelium (RPE); outer segment (OS); inner order TMS PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19667973 segment (IS); outer nuclear layer (ONL); outer plexiform layer (OPL); inner nuclear layer (INL); inner plexiform layer (IPL) and ganglion cell layer (GCL). (B) Morphometric analyses of the retinas from ASMase KO and WT mice. Data are expressed as mean � SE; n !3 (WT), !4 (KO) mice. Indicates significant difference (P < 0.05) between responses in WT and ASMase KO PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19668191 mice. doi:10.1371/journal.pone.0133032.g003 No significant difference of c-wave amplitudes was detected between 1 and 2 months old WT mice. In the eye, the RPE is responsible for the daily phagocytosis of photoreceptor outer segments, a process coupled to their daily renewal. Phagocytosed outer segment material enters the RPE lysosomal compartment where it is degraded. Undigested material accumulates in the form of lipofuscin granules. Excessive accumulation of lipofuscin is associated with retinal degeneration [29, 30]. We therefore examined lipofuscin accumulation in the RPE of WT, ASMase heterozygous knockout (ASMase+/-) and ASMase homozygous knockout (ASMase-/-) mice at 6 months-of- age (Fig 5A�5C). RPE cells from 6-month-old WT and ASMase+/- mice show significant accumulation of lipofuscin granules (Fig 5A and 5B). Ther