OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring.

Lysosomal positioning and mTOR (mammalian target of rapamycin) signaling coordinate cellular responses to nutrient levels. Inadequate nutrient sensing can result in growth delays, a hallmark of Lowe syndrome. OCRL mutations cause Lowe syndrome, but the role of OCRL in nutrient sensing is unknown.

Defective INPP5E distribution in NPHP1-related Senior-Loken syndrome.

Background: Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin-1, which functions at the transition zone (TZ) of primary cilia.

Developmental distribution of primary cilia in the retinofugal visual pathway.

The mammalian visual system is composed of circuitry connecting sensory input from the retina to the processing core of the visual cortex. The two main retinorecipient brain targets, the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN), bridge retinal input and visual output. The primary cilium is a conserved organelle increasingly viewed as a critical sensor for the regulation of developmental and homeostatic pathways in most mammalian cell types.

Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation.

Glaucoma is a group of progressive optic neuropathies that cause irreversible vision loss. Although elevated intraocular pressure (IOP) is associated with the development and progression of glaucoma, the mechanisms for its regulation are not well understood. Here, we have designed CIBN/CRY2-based optogenetic constructs to study phosphoinositide regulation within distinct subcellular compartments.

Endoscopic Cyclophotocoagulation and Other Cyclodestructive Methods: Histopathologic Comparison of In Vivo Treatment in Humans and Monkeys.

Purpose: To compare the histologic effects of endoscopic cyclophotocoagulation (ECP) with other ciliary body ablative procedures. A secondary aim was to correlate these findings with historical clinical success and complication rates.

Design: Prospective, qualitative comparison of histopathologic tissue analysis.

Intraluminal Deposits Found in Glaucoma Tube Shunts Via Anterior Segment Ocular Coherence Tomography.

Purpose: To describe and characterize a novel observation of intraluminal deposits of glaucoma tube shunts (TS) using spectral domain (SD) ocular coherence topography (OCT).

Patients And Methods: Fifteen TS in 11 patients diagnosed with primary open-angle, neovascular, aphakic, and uveitic glaucomas. Both Ahmed (n=11) and Baerveldt (n=4) TS were examined with 5-line raster anterior segment SD-OCT imaging.

Loss of OCRL increases ciliary PI(4,5)P in Lowe oculocerebrorenal syndrome.

Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane is poorly understood.

Ocular Pathology of Oculocerebrorenal Syndrome of Lowe: Novel Mutations and Genotype-Phenotype Analysis.

Mutations in the OCRL1 gene result in the oculocerebrorenal syndrome of Lowe, with symptoms including congenital bilateral cataracts, glaucoma, renal failure, and neurological impairments. OCRL1 encodes an inositol polyphosphate 5-phosphatase which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P). We have identified two novel mutations in two unrelated Lowe syndrome patients with congenital glaucoma.

Drawing sounds: representing tones and chords spatially.

Research on the crossmodal correspondences has revealed that seemingly unrelated perceptual information can be matched across the senses in a manner that is consistent across individuals. An interesting extension of this line of research is to study how sensory information biases action. In the present study, we investigated whether different sounds (i.

Management of plateau iris syndrome with cataract extraction and endoscopic cyclophotocoagulation.

Plateau iris configuration describes an anatomic abnormality in which large or anteriorly positioned pars plicata push the iris root forward, thereby narrowing the anterior chamber angle. Plateau iris syndrome (PIS) is diagnosed if the angle remains occludable, either spontaneously or pharmacologically, after iridotomy. PIS has traditionally been treated with chronic pilocarpine or laser peripheral iridoplasty.

Profiling of Cytokines Secreted by Conventional Aqueous Outflow Pathway Endothelial Cells Activated In Vitro and Ex Vivo With Laser Irradiation.

Purpose: To profile which cytokine genes are differentially expressed (DE) as up- or downregulated by cultured human trabecular meshwork (TMEs) and Schlemm's canal endothelial cells (SCEs) after three experimental treatments consisting of selective laser trabeculoplasty (SLT) irradiation, exposure to media conditioned either by SLT-irradiated TMEs (TME-cm) or by SCEs (SCE-cm). Also, to profile which cytokines are upregulated ex vivo in SLT-irradiated human conventional aqueous outflow pathway (CAOP) tissues.

Methods: After each treatment, Affymetrix microarray assays were used to detect upregulated and downregulated genes for cytokines and their receptors in TMEs and SCEs.

The sweetest thing: the influence of angularity, symmetry, and the number of elements on shape-valence and shape-taste matches.

A within-participants experiment was conducted in two countries (the UK and Colombia) in order to investigate the matching of shapes to taste words. Comparing the two countries allowed us to explore some of the cultural differences that have been reported thus far solely in terms of people's visual preferences. In particular, we addressed the question of whether properties other than angularity influence shape-valence and shape-taste matching (crossmodal correspondences).

Assessment of the effect of time in the repeatability of the stabilometric parameters in diabetic and non-diabetic subjects during bipedal standing using the LorAn pressure distribution measurement system.

This study was designed to assess the effect of time on the repeatability of the LorAn pressure distribution measurement system, and evaluate the variability of plantar pressure and postural balance, during barefoot standing in diabetic and non-diabetic subjects, for future diabetic foot clinical evaluation. Fourteen subjects were evaluated (8 females, 6 males, 8 non-diabetics and 6 diabetics, age range 30-70 years) and had no musculoskeletal symptoms. Four variables were measured with the platform in the barefoot standing position.

Similar effects of selective laser trabeculoplasty and prostaglandin analogs on the permeability of cultured Schlemm canal cells.

Purpose: To evaluate whether selective laser trabeculoplasty and prostaglandin analogs regulate the permeability of cultured human Schlemm canal cells by inducing intercellular junction disassembly.

Design: Laboratory investigation.

Methods: Intercellular junctions were made visible in living cells by making them fluoresce after transfection with a plasmid expressing the zonula occludens 1 protein tagged with green fluorescent protein.

Monocyte modulation of aqueous outflow and recruitment to the trabecular meshwork following selective laser trabeculoplasty.

Objectives: To determine whether selective laser trabeculoplasty (SLT) induces monocyte recruitment to the trabecular meshwork (TM) in human and monkey eyes and whether monocytes increase both aqueous outflow in vivo and the conductivity of human Schlemm canal endothelial cells (SCEs) in vitro.

Methods: Monocyte recruitment was examined morphometrically in control human and monkey eyes and compared with that following SLT applied 1 to 3 days earlier. Outflow facility was measured for up to 4 days after the intracameral infusion of autologous macrophages in rabbits.

Constitutive secretion of chemokines by cultured human trabecular meshwork cells.

Trabecular meshwork endothelial (TME) cells secrete a number of factors, such as enzymes and cytokines, which modulate the functions of the cells and the extracellular matrix of the conventional aqueous outflow pathway. TME cells usually secrete these factors in response to stimuli such as mechanical stretching, laser irradiation and pro-inflammatory cytokines. Here, we report that cultured human TME cells isolated from two non-glaucomatous individuals secrete significant quantities of the chemotactic cytokines IL8, CXCL6 and MCP1 in the absence of any stimulation.

From the bedside to the bench and back again: predicting and improving the outcomes of SLT glaucoma therapy.

Purpose: To determine whether selective laser trabeculoplasty (SLT) and prostaglandin analogues (PGAs) have a common mechanism of action that involves increasing conductivity across Schlemm's canal endothelial cells (SCEs) and inducing a similar decrease in intraocular pressure (IOP) in a given patient.

Methods: The intercellular junctions in SCEs were made visible by transfection of a plasmid containing a GFP-tagged gene for ZO-1 protein. Transfected SCEs were treated with media conditioned by lasered trabecular meshwork endothelial cells (TMEs), or with latanoprost, bimatoprost, or travoprost.

Hypotony maculopathy after eyelid massage for overcorrected blepharoptosis.

A 57-year-old woman with a history of left eye trabeculectomy was evaluated for gradual ipsilateral visual loss. Several months prior, she had undergone levator advancement of the left upper eyelid. For management of resulting retraction, she was instructed to "massage" her eyelid.

Ahmed valve implantation with adjunctive mitomycin C and 5-fluorouracil: long-term outcomes.

Purpose: To evaluate long-term outcomes after Ahmed valve implantation in patients with glaucoma when using adjunctive intraoperative mitomycin C (MMC) and postoperative 5-fluorouracil (5-FU).

Design: Retrospective, interventional, consecutive case series.

Methods: A consecutive series of eyes undergoing Ahmed valve implantation, either alone (AHMED eyes) or in combination with cataract surgery (AHMED+PHACO), using both intraoperative MMC and postoperative 5-FU were evaluated.

Genotype and phenotype correlations in congenital glaucoma.

Purpose: To determine whether there is a correlation among mutations in the cytochrome P450 1B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma.

Methods: Direct DNA sequencing was utilized to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway.

Genotype and phenotype correlations in congenital glaucoma: CYP1B1 mutations, goniodysgenesis, and clinical characteristics.

Purpose: To determine whether there is a correlation among mutations in the cytochrome P4501B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma.

Design: Interventional case series.

Methods: Direct DNA sequencing was used to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations.

Interactions between endothelia of the trabecular meshwork and of Schlemm's canal: a new insight into the regulation of aqueous outflow in the eye.

Purpose: To test the hypothesis that trabecular meshwork endothelial cells (TMEs) regulate aqueous outflow by actively releasing ligands that upon binding to Schlemm's canal endothelial cells (SCEs) increase transendothelial flow, thereby facilitating the egress of aqueous.

Methods: We tested our hypothesis by (1) activating the TMEs in vitro using a laser procedure known to increase aqueous outflow in vivo; (2) demonstrating that lasered TMEs become activated at the genome-wide level and synthesize ligands; (3) ascertaining that media conditioned by laser-activated TMEs and ligands therein increase transendothelial flow when added to SCEs; and (4) determining that ligands identified as synthesized by TMEs increase permeability when added to SCEs.

Results: We find that adding either media conditioned by lasered TMEs or ligands synthesized by TMEs to naïve control SCEs increases permeability.