Rapid Intraocular Tube Trimming for Glaucoma Drainage Implant Devices.

PURPOSE: To describe a new approach for shortening silicone tubes of glaucoma drainage devices (GDDs). MATERIALS AND METHODS: A retrospective intervention case series describing 3 patients undergoing the same treatment at a single institutional center RESULTS:: Three patients underwent successful ab interno trimming of GDD silicone tubes without complication CONCLUSIONS:: This technique allows for rapid and successful shortening of GDD tubes via an ab interno approach avoiding risks of traditional glaucoma tube trimming approaches.

First Described Case of Anterior and Posterior Segment Crystals in Phacolytic Glaucoma.

Phacolytic glaucoma is an open-angle glaucoma that occurs when lens proteins from hypermature cataracts seep through an intact anterior capsule and induce obstruction of the trabecular meshwork by inflammatory cells. We review the case of a 66-year-old man who presented with acute pain, a hypermature cataract, prominent anterior chamber crystals, and elevated intraocular pressure. After cataract surgery was performed, iridescent crystals were noted in the posterior chamber. Anterior chamber crystals have been associated with phacolytic glaucoma, but this is the first case demonstrating crystals in the posterior chamber as well.

BRANCH RETINAL ARTERY OCCLUSION ASSOCIATED WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY IN A PATIENT WITH LIVEDO RETICULARIS.

PURPOSE: To report the occurrence of a branch retinal artery occlusion with paracentral acute middle maculopathy in an otherwise healthy young man with a history of livedo reticularis (LR). METHODS: Retrospective case report. PATIENTS: A 21-year-old man with a history of LR being treated with pentoxifylline developed an acute branch retinal artery occlusion with initial best-corrected visual acuity at presentation of 20/80. RESULTS: A thorough diagnostic work up was negative for potential causes of branch retinal artery occlusion or LR. The patient was continued on pentoxifylline and started on aspirin 81 mg daily. At five-month follow-up, vision had improved to 20/25. Optical coherence tomography testing showed a hyperreflective band in the inner nuclear layer and outer plexiform layers in the affected eye that ultimately thinned, consistent with paracentral acute middle maculopathy. CONCLUSION: To our knowledge, this is the first case of branch retinal artery occlusion occurring in a patient with a history of LR. This could potentially be an early manifestation of Sneddon syndrome, a rare entity characterized by LR and cerebrovascular disease, which has been previously associated with central retinal artery occlusions.

First Reported Case of Proliferative Retinopathy in Hemoglobin SE Disease.

We report the first case of proliferative sickle cell retinopathy in a patient with hemoglobin SE (Hb SE) disease. Only a few dozen cases of Hb SE disease have been reported previously, and none had evidence of proliferative retinopathy. A 56-year-old African American man presented to our clinic for routine examination and was found to have sea-fan peripheral neovascularization bilaterally without maculopathy. Hemoglobin analysis revealed Hb SE heterozygosity. Sector laser photocoagulation to areas of nonperfusion in both eyes resulted in regression of the peripheral neovascularization over a period of 6 months. Although Hb SE disease is rare, the incidence of Hb SE disease is postulated to rise in the future. Awareness of its potential ocular complications is needed to appropriately refer these patients for screening.

Merkel cell carcinoma dependence on bcl-2 family members for survival.

Merkel cell carcinoma (MCC), a rare but aggressive cutaneous neoplasm with high metastatic potential, has a poor prognosis at late stages of disease with no proven chemotherapeutic regimens. Using an enriched culture medium, we established and characterized 11 MCC cell lines for Bcl-2 family profiling and functional studies. Immunoblot analysis revealed collectively high protein levels of prosurvival Bcl-2 members in cell lines and a panel of MCC tumors. Downregulation of individual Bcl-2 proteins by RNAi promoted death in a subset of MCC cell lines, whereas simultaneous inhibition of multiple family members by using the small-molecule antagonist ABT-263 led to a marked induction of cell death in 10 of 11 lines. ABT-263 induced Bax-dependent apoptosis with rapid cleavage of caspase-3 and PARP, regardless of Bcl-2 family profile or the presence of Merkel cell polyomavirus. Furthermore, ABT-263 treatment led to rapid and sustained growth suppression of MCC xenografts from a representative cell line, accompanied by a striking increase in apoptosis. Our results establish that concurrent inhibition of multiple prosurvival Bcl-2 proteins leads to effective induction of apoptosis, and strongly support the concept that targeting MCC dependence on these molecules may be useful therapeutically by reversing an intrinsic resistance to cell death.

A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins.

Mammalian telomeres are protected by a six-protein complex: shelterin. Shelterin contains two closely related proteins (TRF1 and TRF2), which recruit various proteins to telomeres. We dissect the interactions of TRF1 and TRF2 with their shared binding partner (TIN2) and other shelterin accessory factors. TRF1 recognizes TIN2 using a conserved molecular surface in its TRF homology (TRFH) domain. However, this same surface does not act as a TIN2 binding site in TRF2, and TIN2 binding to TRF2 is mediated by a region outside the TRFH domain. Instead, the TRFH docking site of TRF2 binds a shelterin accessory factor (Apollo), which does not interact with the TRFH domain of TRF1. Conversely, the TRFH domain of TRF1, but not of TRF2, interacts with another shelterin-associated factor: PinX1.

The POT1-TPP1 telomere complex is a telomerase processivity factor.

Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 (protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.