Biochemistry/Molecular Biology - ARVO

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Biochemistry/Molecular Biologyoutcomes included difference between initial best corrected visualacuity (BCVA) and best BCVA during follow up, integrity of IS-OSjunction, and integrity of foveal capillary ring.Results: In the bevacizumab group, average improvement in BCVAwas 0.375 +/- 0.205 logMAR. Best BCVA was achieved on averageafter 2.2 +/- 1.6 months and 1.4 +/- 1.1 intravitreal injections. In theranibizumab group, average improvement in BCVA was 0.141 +/-0.151 logMAR. Best BCVA was achieved on average after 2.4 +/-2.2 months and 2.0 +/- 1.7 intravitreal injections. In the bevacizumabgroup, average improvement in CMT was 404 +/- 41 um with bestCMT occurring on average after 1.1 +/- 0.1 months and 1.0 +/- 0.0injections. In the ranibizumab group, average improvement in CMTwas 286 +/- 47 um with best CMT occurring on average after 2.7 +/-1.1 months and 2.5 +/- 0.7 injections.Conclusions: Bevacizumab may be superior to ranibizumab fortreating BRVO with greater improvement in BCVA, fewer injectionsto achieve best BCVA, fewer injections needed during follow upcourse, greater improvement in CMT, shorter time interval to bestCMT, and fewer injections needed to achieve best CMT. Theintegrity of the IS-OS junction correlated well with visual acuityresponse to anti-VEGF treatment. The integrity of the foveal capillaryring in relation to visual outcome was equivocal. Statisticalsignificance was limited by the small sample size.Commercial Relationships: Peng Lei, NoneProgram Number: 1130 Poster Board Number: D0034Presentation Time: 1:00 PM - 2:45 PMVEGF and TNF Interact to Induce Retinal Edema in an AtypicalPKC Dependent MannerCheng-mao Lin 1 , Paul M. Titchenell 2 , Arivalagan Muthusamy 1 ,David A. Antonetti 1 . 1 Ophthalmology and Visual Sciences, KelloggEye Center, University of Michigan, Ann Arbor, MI; 2 Cellular andMolecular Physiology, Penn State College of Medicine, Hershey, PA.Purpose: Changes in permeability of retinal blood vessels contributeto macular edema and the pathophysiology of diabetic retinopathy.Both vascular endothelial growth factor (VEGF) and tumor necrosisfactor (TNF) have been implicated in macular edema. We tested thehypothesis that VEGF and TNF interact to induce retinal edema invivo and require atypical PKC (aPKC) activation.Methods: Male Long-Evans rats weighing 200 to 250 g were used toevaluate retinal vascular permeability and retinal thickening inducedby VEGF and TNF treatments. Animals received a single intravitrealinjection of vehicle, aPKC inhibitor, VEGF, TNF, combined VEGFand TNF or VEGF/TNF plus aPKC inhibitor to yield finalconcentration as indicated. Blood-retinal barrier leakage wasmeasured with intravenous FITC-BSA injection. Retinal leakage wascalculated from the accumulation of fluorescent albumin in the retinaand normalized to the plasma levels. Also, 5 h after intraocularinjection of the same factors, eyes were imaged 10 min after FITC-BSA injection for retinal vascular leakage using a Micron III camera.Eyes were then enucleated, fixed and subjected to flat-mount stainingfor subsequent imaging. Tight junction proteins were examined byimmunohistochemistry. Retinal structure and layer thickness, ameasure of edema, were assessed with spectral domain opticalcoherence tomography. Baseline data were obtained before anytreatment and used for comparison with the later time points in thelongitudinal study.Results: Partial discontinuity of occludin and ZO-1 immunostainingwas observed in the VEGF-treated retinas, whereas loss of ZO-1wasobserved in the TNF-treated retinas. VEGF/TNF combinationtreatment dramatically induced tight junction disorganization andinteracted to increase retinal thickening. Increased retinal albuminleakage and retinal thickening induced by combined VEGF/TNFtreatment were effectively prevented by an aPKC inhibitor in a dosedependentmanner. In the longitudinal study, aPKC inhibitionattenuated the initial (24 h) edema response from VEGF/TNFadministration by 40%. The group treated with the aPKC inhibitorreturned to baseline more rapidly than VEGF/TNF group.Conclusions: These data demonstrate that VEGF and TNF interact topromote retinal edema in vivo and provide an effective model to testtherapeutic intervention to control edema. Co-injection of aPKCinhibitor dramatically reduces induction of edema in vivo.Commercial Relationships: Cheng-mao Lin, None; Paul M.Titchenell, None; Arivalagan Muthusamy, None; David A.Antonetti, NoneSupport: JDRFProgram Number: 1131 Poster Board Number: D0035Presentation Time: 1:00 PM - 2:45 PMThe Role of Apelin in the Retina of Diabetic RatsYanrong Jiang, Qiang Lu, Jing Feng. Peking University People'sHospital, Beijing, China.Purpose: The purpose of this study was to investigate the effect ofapelin-13 on proliferative potential in diabetic retinopathy (DR), andits antagonist inhibitory effects.Methods: Localization of apelin-13, GFAP, and VEGF weredetected using immunofluorescence in the retina of diabetic rats. ThemRNA and protein of apelin-13, GFAP, and VEGF in the retina ofdiabetic rats were measured using real-time PCR and western blot.Apelin-13 antagonist F13A was used to block apelin-13, and to studyits effects in vivo.Results: Strong staining of apelin-13, co-localized with GFAP andVEGF, was observed in the retina of diabetic rats. Apelin-13, GFAP,and VEGF mRNA and protein levels were significantly increased inthe sample’s retina. Moreover, exogenous apelin-13 promoted retinalMüller cell proliferation in vivo. Simultaneously, apelin-13 inducedGFAP and VEGF expression. F13A markedly reduced the retinalgliosis caused by diabetes. Furthermore, F13A suppressed bothGFAP and VEGF expression in vivo.Conclusions: Our results strongly suggest that apelin-13 is associatedwith the development of DR, and contributes to changes in the retinaof diabetic rats. Apelin-induced promotion of cell proliferation lendssupport to the possibility that apelin-13 may play a role in theprogression of DR to a proliferative phase. This possible roledeserves further investigation, which may open new perspectives inthe early prevention and treatment of DR.©2013, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permissionto reproduce any abstract, contact the ARVO Office at arvo@arvo.org.