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Los Angeles, CA, United States

Sun H.,Jules Stein Eye Institute
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2012

The eye is the human organ most sensitive to vitamin A deficiency because of vision's absolute and heavy dependence on vitamin A for light perception. Studies of the molecular basis of vision have provided important insights into the intricate mechanistic details of the function, transport and recycling of vitamin A and its derivatives (retinoid). This review focuses on retinoid-related membrane receptors and transporters. Three kinds of mammalian membrane receptors and transporters are discussed: opsins, best known as vitamin A-based light sensors in vision; ABCA4, an ATP-dependent transporter specializes in the transport of vitamin A derivative; and STRA6, a recently identified membrane receptor that mediates cellular uptake of vitamin A. The evolutionary driving forces for their existence and the wide spectrum of human diseases associated with these proteins are discussed. Lessons learned from the study of the visual system might be useful for understanding retinoid biology and retinoid-related diseases in other organ systems as well. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. © 2011 Elsevier B.V.

Matynia A.,Jules Stein Eye Institute
Experimental eye research | Year: 2012

Photoallodynia (photophobia) occurs when normal levels of light cause pain ranging from uncomfortable to debilitating. The only current treatment for photoallodynia is light avoidance. The first step to understanding the mechanisms of photoallodynia is to develop reliable animal behavioral tests of light aversion and identify the photoreceptors required to initiate this response. A reliable light/dark box behavioral assay was developed that measures light aversion independently from anxiety, allowing direct testing of one endophenotype of photoallodynia in mice. Mice lacking intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit reduced aversion to bright light, suggesting these cells are the primary circuit for light aversion. Mice treated with exogenous μ opiate receptor agonists exhibited dramatically enhanced light aversion, which was not dependent on ipRGCs, suggesting an alternative pathway for light is engaged. Morphine enhances retinal electrophysiological responses to light but only at low levels. This suggests that for the dramatic light aversion observed, opiates also sensitize central brain regions of photoallodynia. Taken together, our results suggest that light aversion has at least two dissociable mechanisms by which light causes specific allodynia behaviors: a primary ipRGC-based circuit, and a secondary ipRGC-independent circuit that is unmasked by morphine sensitization. These models will be useful in delineating upstream light sensory pathways and downstream avoidance pathways that apply to photoallodynia. Published by Elsevier Ltd.

Khurana R.N.,Northern California Retina Vitreous Associates | Khurana R.N.,University of California at San Francisco | Appa S.N.,Southern California Permanente Medical Group | McCannel C.A.,Jules Stein Eye Institute | And 5 more authors.
Ophthalmology | Year: 2014

Objective To describe the risk factors, clinical course, and complications of migration of a dexamethasone (DEX) intravitreal implant (OZURDEX; Allergan, Inc., Irvine, CA) into the anterior chamber and subsequent management strategies. Design Retrospective, observational case series. Participants Fifteen patients had 18 episodes of migration of the DEX implant into the anterior chamber. Methods The medical records of 15 patients with spontaneous migration of a DEX implant were retrospectively reviewed. Main Outcome Measures Migration of the DEX implant into the anterior chamber. Results Migration of a DEX intravitreal implant into the anterior chamber occurred in 6 patients who were aphakic, 4 patients with an anterior chamber intraocular lens, 2 patients with a scleral-fixated posterior chamber intraocular lens (PCIOL), 2 patients with a PCIOL, and 1 patient with an iris-fixated PCIOL. All 15 patients had prior pars plana vitrectomy, and 14 patients (93%) had no lens capsule. The average interval from DEX implant injection to detection of the implant migration into the anterior chamber was 13 days (range, 5-44 days). In 14 patients, corneal edema developed. Among those eyes undergoing surgical removal of the implant, earlier intervention reduced the likelihood of permanent corneal edema (0.5 days [from diagnosis of migration to surgical removal of the implant] vs. 5.5 days; P = 0.04). Aspiration was necessary to remove the implant in 6 patients. Among the 14 patients with corneal edema, the corneal edema did not resolve in 10 patients (71%), 6 (43%) of whom required corneal transplantation. Conclusions Absence of lens capsule and prior vitrectomy are risk factors for migration of the DEX implant into the anterior chamber. Early removal of the implant may be necessary to minimize the risk of chronic corneal edema. © 2014 by the American Academy of Ophthalmology.

Gorin M.B.,University of California at Los Angeles | Gorin M.B.,Jules Stein Eye Institute
Molecular Aspects of Medicine | Year: 2012

Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews (Chen et al.; 2010b; Deangelis et al.; 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al.; 2011). Large meta analysis of AMD GWAS has added new loci and variants to this collection (Chen et al.; 2010a; Kopplin et al.; 2010; Yu et al.; 2011). This paper will focus on the ongoing controversies that are confronting AMD genetics at this time, rather than attempting to summarize this field, which has exploded in the past 5 years. © 2012 Elsevier Ltd. All rights reserved.

Srikumaran D.,Wilmer Eye Institute | Munoz B.,Wilmer Eye Institute | Aldave A.J.,Jules Stein Eye Institute | Aquavella J.V.,Flaum Eye Institute | And 4 more authors.
Ophthalmology | Year: 2014

Design Retrospective, multicenter case series.ParticipantsA total of 158 eyes of 150 patients underwent KPro implantation at 5 participating tertiary centers in the United States between January 2003 and December 2006. Of those, 139 eyes of 133 patients were included in the analyses.Purpose To study the long-term outcomes of Boston type 1 keratoprosthesis (KPro) surgery.Methods The medical records of consecutive adult patients who received KPro surgery were reviewed. All patients with at least 1 postoperative visit were retained in the outcomes analyses. In eyes in which a repeat KPro procedure was performed, only the outcomes of the initial surgery were analyzed.Main Outcome Measures Visual acuity (VA) outcomes, postoperative complications, and device retention.Results The mean follow-up was 46.7±26 months with all but 4 eyes having at least 6 months of follow-up. Preoperatively, only 10.8% of the eyes had VA of ≥20/200. Postoperatively, the VA in 70% of eyes improved to ≥20/200. The probability of maintaining VA of ≥20/200 at 7 years was 50%. The device retention rate was estimated at 67% at 7 years. The 7-year cumulative incidence of complications was 49.7% for retroprosthetic membrane formation, 21.6% for glaucoma surgery, 18.6% for retinal detachment, and 15.5% for endophthalmitis.Conclusions Although the risk for complications with longer follow-up seemed to increase, this large multicenter cohort demonstrates favorable outcomes with KPro, with a large number of patients achieving and retaining useful vision over a 7-year period. © 2014 American Academy of Ophthalmology.

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