Proteomic analyses of retina of excitatory amino acid carrier 1 deficient mice.

BACKGROUND: Excitatory amino acid carrier 1 (EAAC1) is a glutamate transporter found in neuronal tissues and is extensively expressed in the retina. EAAC1 plays a role in a variety of neural functions, but its biological functions in the retina has not been fully determined. The purpose of this study was to identify proteins regulated by EAAC1 in the retina of mice. To accomplish this, we used a proteomics-based approach to identify proteins that are up- or down-regulated in EAAC1-deficient (EAAC1-/-) mice. RESULTS: Proteomic analyses and two-dimensional gel electorphoresis were performed on the retina of EAAC1-/- mice, and the results were compared to that of wild type mice. The protein spots showing significant differences were selected for identification by mass spectrometric analyses. Thirteen proteins were differentially expressed; nine proteins were up-regulated and five proteins were down-regulated in EAAC1-/- retina. Functional clustering showed that identified proteins are involved in various cellular process, e.g. cell cycle, cell death, transport and metabolism. CONCLUSION: We identified thirteen proteins whose expression is changed in EAAC-/- mice retinas. These proteins are known to regulate cell proliferation, death, transport, metabolism, cell organization and extracellular matrix.

A polymorphism of LOC387715 gene is associated with age-related macular degeneration in the Japanese population.

Age-related macular degeneration (AMD) is one of the leading causes of blindness among older adults in developed countries and also in Japan. Previous research suggests that AMD is etiologically a complex disease, caused by multiple genes and environmental factors. Association studies have identified that a complement factor H gene (CFH) variant is a major risk factor for AMD in Caucasians. However, we and two other groups have reported no association between CFH and AMD in the Japanese population. Recent studies have suggested that LOC387715 on chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this study, we examined the association between LOC387715 and AMD in Japanese, and our results show that polymorphism of the LOC387715 gene is associated with AMD in Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20 (95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715 compared with the non-risk genotype. A polymorphism of LOC387715 gene is associated with AMD in the Japanese population.

Pigment epithelium-derived factor promotes neurite outgrowth of retinal cells.

The ability of pigment epithelium-derived factor (PEDF) to promote neurite outgrowth of retinal cells through mitogen-activated protein kinase (MAPK) pathways was examined. Neurite outgrowth effects of PEDF were determined by quantifying the neurite length extending from cultured chick embryo retinal explants, and neurite outgrowth ratio of R28 cells (a neural cell line derived from the neonatal rat retina). MAPK activity levels were determined by inhibition assays. The contribution of signaling pathway was quantified with a specific inhibitor for MAPK: PD98059. PEDF (50 ng/ml) promoted chick retinal neurite elongation and increased the extent of R28 cell neurite outgrowth. PD98059 decreased neurite elongation of chicken retinal explants and the extent of R28 cell neurite outgrowth. PEDF possibly promotes neurite outgrowth for retinal cells by activating MAPK pathways. These data suggest that PEDF provides a useful support for retinal cells through the MAPK pathway and leads to the progress of therapy for many retinal diseases.