Memorizing critical objects and their locations is an essential part of everyday life. In the present study, incidental encoding of objects in naturalistic scenes during search was compared to explicit memorization of those scenes. To investigate if prior knowledge of scene structure influences these two types of encoding differently, we used meaningless arrays of objects as well as objects in real-world, semantically meaningful images. Surprisingly, when participants were asked to recall scenes, their memory performance was markedly better for searched objects than for objects they had explicitly tried to memorize, even though participants in the search condition were not explicitly asked to memorize objects. This finding held true even when objects were observed for an equal amount of time in both conditions. Critically, the recall benefit for searched over memorized objects in scenes was eliminated when objects were presented on uniform, non-scene backgrounds rather than in a full scene context. Thus, scene semantics not only help us search for objects in naturalistic scenes, but appear to produce a representation that supports our memory for those objects beyond intentional memorization.

PURPOSE: To evaluate the mechanism of tamoxifen-induced cell death in human cultured RPE cells, and to investigate concurrent cell death mechanisms including pyroptosis, apoptosis, and necroptosis. METHODS: Human RPE cells were cultured until confluence and treated with tamoxifen; cell death was measured by detecting LDH release. Tamoxifen-induced cell death was further confirmed by 7-aminoactinomycin D (7-AAD) and annexin V staining. Lysosomal destabilization was assessed using lysosomal-associated membrane protein-1 (LAMP-1) and acridine orange staining. The roles of lysosomal enzymes cathepsin B and L were examined by blocking their activity. Caspase activity was evaluated by caspase-1, -3, -8, and -9 specific inhibition. Cells were primed with IL-1α and treated with tamoxifen; mature IL-1β production was quantified via ELISA. Caspase activity was verified with the fluorochrome-labeled inhibitor of caspases (FLICA) probe specific for each caspase. Regulated cell necrosis or necroptosis was examined with 7-AAD and inhibition of receptor-interacting protein 1 (RIP1) kinase using necrostatin-1 (Nec-1). RESULTS: Cell death occurred within 2 hours of tamoxifen treatment of confluent RPE cells and was accompanied by lysosomal membrane permeabilization. Blockade of cathepsin B and L activity led to a significant decrease in cell death, indicating that lysosomal destabilization and cathepsin release occur prior to regulated cell death. Tamoxifen-induced toxicity was shown to occur through both caspase-dependent and caspase-independent cell death pathways. Treatment of RPE cells with caspase inhibitors and Nec-1 resulted in a near complete rescue from cell death. CONCLUSIONS: Tamoxifen-induced cell death occurs through concurrent regulated cell death mechanisms. Simultaneous inhibition of caspase-dependent and caspase-independent cell death pathways is required to protect cells from tamoxifen. Inhibition of upstream activators, such as the cathepsins, may represent a novel approach to block multiple cell death pathways.

In glaucoma, regardless of its etiology, retinal ganglion cells degenerate and eventually die. Although age and elevated intraocular pressure (IOP) are the main risk factors, there are still many mysteries in the pathogenesis of glaucoma. The advent of genome-wide microarray expression screening together with the availability of animal models of the disease has allowed analysis of differential gene expression in all parts of the eye in glaucoma. This review will outline the findings of recent genome-wide expression studies and discuss their commonalities and differences. A common finding was the differential regulation of genes involved in inflammation and immunity, including the complement system and the cytokines transforming growth factor β (TGFβ) and tumor necrosis factor α (TNFα). Other genes of interest have roles in the extracellular matrix, cell-matrix interactions and adhesion, the cell cycle, and the endothelin system.

UNLABELLED: We present a case of corneal perforation secondary to an intrastromal astigmatic keratotomy performed with an optical coherence tomography-guided femtosecond laser. The keratotomy was concomitant with cataract surgery and resulted in a flat anterior chamber prior to the start of lens extraction. Interrupted nylon sutures were placed to seal the keratotomy prior to phacoemulsification. Escape of cavitation bubbles into the anterior chamber or the liquid interface can alert the surgeon to the possibility of unintended perforation of the endothelium or the epithelium, respectively. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

The aim of this study was to describe a transnasal endoscopic bimanual technique for the removal of an intraconal orbital apex cavernous hemangioma. Report of a surgical technique. A 39-year-old woman with unilateral visual loss and proptosis was found to have an intraconal orbital apex mass consistent radiographically with cavernous hemangioma. Because of its posteromedial location within the orbit, a transnasal 4-handed endoscopic technique was used with pedicled nasoseptal flap reconstruction. The tumor was excised, and the patient had no complications. The transnasal endoscopic approach to orbital apex cavernous hemangioma excision is a viable surgical approach for these difficult to access lesions. The medial orbital wall may be simultaneously reconstructed to prevent diplopia and enophthalmos.