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Extended Conformation of the Proline-rich Domain of Human Aryl Hydrocarbon Receptor-Interacting Protein-like 1: Implications for Retina Disease.
J Neurochem. 2015 Jul 1;
Authors: Yadav RP, Majumder A, Gakhar L, Artemyev NO
Mutations in the primate-specific proline-rich domain (PRD) of aryl hydrocarbon receptor-interacting protein-like 1(AIPL1) are thought to cause Leber congenital amaurosis or dominant cone-rod dystrophy. The role of PRD and the mechanisms of PRD mutations are poorly understood. Here, we have examined properties of hAIPL1 and effects of the PRD mutations on protein structure and function. Solution structures of hAIPL1, hAIPL11-316 with PRD truncation, and the P351Δ12 and P376S mutants were examined by Small Angle X-ray Scattering. Our analysis suggests that PRD assumes an extended conformation and does not interact with the FK506-binding and tetratricopeptide domains. The PRD truncation, but not PRD mutations, reduced the molecule's radius of gyration and maximum dimension. We demonstrate that hAIPL1 is a monomeric protein, and its secondary structure and stability are not affected by the PRD mutations. PRD itself is an extended monomeric random coil. The PRD mutations caused little or no changes in hAIPL1 binding to known partners, phosphodiesterase-6A and HSP90. We also identified the γ-subunit of phosphodiesterase-6 as a novel partner of hAIPL1 and hypothesize that this interaction is altered by P351Δ12. Our results highlight the complexity of mechanisms of PRD mutations in disease and the possibility that certain mutations are benign variants. This article is protected by copyright. All rights reserved.
PMID: 26139345 [PubMed - as supplied by publisher]
Stability and safety of MA50 intraocular lens placed in the sulcus.
Eye (Lond). 2015 Jul 3;
Authors: Kemp PS, Oetting TA
PurposeTo describe the safety and stability of sulcus placement of the MA50 intraocular lens (IOL).Patients and methodsConsecutive patients with MA50 IOLs placed in the sulcus at the University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA, from 1997 to 2012 were identified. Inclusion criteria included patients with over 4 weeks of follow-up data. AEL was compared with incidence of IOL decentration using at two-tailed Student's t-test.ResultsFifty eyes of 49 patients meeting the inclusion criteria were identified. Four weeks post-operatively, the average best-corrected visual acuity was 20/30. IOL decentration occurred in 14% of patients; patients with decentered IOLs had a significantly longer average AEL (25.37 mm) than patients whose IOL remained centered (23.94 mm, P=0.017). Other complications included uveitis-glaucoma-hyphema syndrome (12%), iritis (8%), and glaucoma (6%). There were no cases of pigment dispersion syndrome or need for lens exchange. Twelve eyes (24%) had intra-operative optic capture by the anterior capsule, none of which had post-operative decentration.ConclusionThe MA50 IOL is a reasonable, stable option for placement in the sulcus, with a low-risk profile; however, in eyes with longer AEL and presumably larger anterior segment, surgeons should consider placing an IOL with longer haptic distance than the MA50 to maintain centration. Optic capture of the MA50 IOL by the anterior capsule should be considered for longer eyes, as it is protective against decentration.Eye advance online publication, 3 July 2015; doi:10.1038/eye.2015.105.
PMID: 26139047 [PubMed - as supplied by publisher]
Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study.
Sci Rep. 2015;5:11791
Authors: Sohn EH, Jiao C, Kaalberg E, Cranston C, Mullins RF, Stone EM, Tucker BA
Stem cell strategies focused on replacement of RPE cells for the treatment of geographic atrophy are under intense investigation. Although the eye has long been considered immune privileged, there is limited information about the immune response to transplanted cells in the subretinal space of large animals. The purpose of this study was to evaluate the survival of allogenic induced pluripotent stem cell-derived RPE cells (iPSC-RPE) delivered to the subretinal space of the pig as well as determine whether these cells induce an immune response in non-diseased eyes. GFP positive iPSC-RPE, generated from outbred domestic swine, were injected into the subretinal space of vitrectomized miniature swine. Control eyes received vehicle only. GFP positive iPSC-RPE cells were identified in the subretinal space 3 weeks after injection in 5 of 6 eyes. Accompanying GFP-negative cells positive for IgG, CD45 and macrophage markers were also identified in close proximity to the injected iPSC-RPE cells. All subretinal cells were negative for GFAP as well as cell cycle markers. We found that subretinal injection of allogenic iPSC-RPE cells into wild-type mini-pigs can induce the innate immune response. These findings suggest that immunologically matched or autologous donor cells should be considered for clinical RPE cell replacement.
PMID: 26138532 [PubMed - as supplied by publisher]