Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in OptineurinPrimary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.
Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cellsSequence Analysis and Homology Modeling Suggest That Primary Congenital Glaucoma on 2p21 Results from Mutations Disrupting Either the Hinge Region or the Conserved Core Structures of Cytochrome P4501B1Ivaylo Stoilov, Nurten Akarsu, Ihuoma Alozie et al.|The American Journal of Human Genetics|1998 Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitroExtracts of saffron (Crocus sativus L.) have been reported to inhibit cell growth of human tumor cells. In order to study the cytotoxic effect of the characteristic compounds of saffron spice, we have isolated crocin, crocetin, picrocrocin and safranal. Doses inducing 50% cell growth inhibition (LD50) on HeLa cells were 2.3 mg/ml for an ethanolic extract of saffron dry stigmas, 3 mM for crocin, 0.8 mM for safranal and 3 mM for picrocrocin. Crocetin did not show cytotoxic effect. Cells treated with crocin exhibited wide cytoplasmic vacuole-like areas, reduced cytoplasm, cell shrinkage and pyknotic nuclei, suggesting apoptosis induction. Considering its water-solubility and high inhibitory growth effect, crocin is the more promising saffron compound to be assayed as a cancer therapeutic agent.
Cloning and characterization of subtracted cDNAs from a human ciliary body library encoding <i>TIGR</i>, a protein involved in juvenile open angle glaucoma with homology to myosin and olfactomedinA group of cDNAs isolated from a subtractive ciliary body library of a normal human eye donor revealed 100% identity with TIGR a candidate gene responsible for juvenile open zangle glaucoma [Science 275 (1997) 668-670]. Several structural features of the deduced human protein have been noted: a cleavable N-terminal signal peptide, a periodic repetition at the N-terminus of leucine and arginine residues at every seventh and eleven position respectively in helix conformation (leucine zipper-like motif) exhibiting homology with myosin, and with olfactomedin in the C-terminus. The mRNA for TIGR is abundantly expressed in the ciliary body, iris, heart and skeletal muscle.