Methyl glyoxal-derived imidazolium cross-link, a lysine-arginine cross-linking structure. Other uncharacterized AGE adducts are also known to exist. That MG and GO can partake in covalent cross-linking of extracellular proteins is significant, since the collagen of Bruch’s membrane is increasingly cross-linked with age. This change in the extracellular matrix is thought to explain altered properties of Bruch’s membrane such as reduced hydraulic conductivity and permeability, enhanced rigidity and thickening. Cultured RPE grown on an AGE-modified basement membrane substrate exhibits reduced tight junctions and changes in mRNA expression including mRNA that encodes proteins involved in cell attachment and immune responses. Protein cross-linking by AGEmodification can also confer resistance to proteolysis, including that mediated by matrix metalloproteinases. CEL and CML along with pentosidine have all been shown to increase with age in human Bruch’s membrane and are reported to be prominent in both neovascular and atrophic AMD. Does bisretinoid photooxidation and photodegradation occur in vivo? Some lines of evidence indicate that indeed these processes occur in the eye. For instance, mono- and bis-peroxy-A2E, monoand bis-furano-A2E, mono and bis-peroxy-all-transretinal dimer and mono- and bis-furano-all-trans-retinal dimer are detected in extracts from human and mouse eyes. The photolysis of bisretinoid at sites of photooxidation could also explain the observation that photooxidized forms of A2E do not accumulate with age. Nevertheless, this is a question that should be addressed in future studies. Some currently ongoing clinical trials aim to develop treatments for age-related macular degeneration based on limiting RPE bisretinoid lipofuscin formation. The results reported here indicate that therapies such as these may have benefits that extend beyond effects on RPE bisretinoid accumulation alone and that could include preservation of Bruch’s membrane integrity. The epithelial to mesenchymal transition is wellcoordinated process during embryonic development as well as progression of cancers including LY2835219 CDK inhibitor colorectal cancers. Epithelial cells gain polarity and motility during EMT, which are necessary for tumor invasion and metastasis in different types of epithelial carcinomas. For example, colorectal cancer cells at the invasive front usually acquire mesenchymal properties including highly migratory, poorly differentiated, hyperproliferative, and loss of cell-cell contact–mediated growth inhibition. SOX2 is one of the key members of the SOX family gene and plays critical role in embryonic stem cells and in induced pluripotent stem cells. It is also involved in invasion and metastasis of pancreatic carcinoma, and in carcinogenesis of gastric, breast, pancreatic cancers, and osteosarcomas and glioma. Furthermore, SOX2 also maintains self-renewal of cancer stem cells or is activated in cancer stem cells. An intriguing question to ask is whether cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells are distinct, overlapping or same populations. Mani et al. reported that induction of EMT in human mammary epithelial cells resulted in the gain of epithelial stem cell properties in HMLEs. We demonstrated for the first time a connection between SOX2 and the Epithelial-Mesenchymal Transition process. During EMT, cells undergo morphological changes from the epithelial polarized morphology to the mesenchymal fibroblastoid morphology. After EMT process, epithelial cells lose cell-cell or cell-substrate contacts, and gain increased migratory capabilities.