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1.
Retina ; 35(10): 1951-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25932561

RESUMO

PURPOSE: To evaluate the influence of vitreomacular attachment on outcomes after intravitreal aflibercept for neovascular age-related macular degeneration. METHODS: In a prospective case series, eyes with neovascular age-related macular degeneration were treated with intravitreal aflibercept, given as 3 consecutive monthly injections, followed by further injection every 2 months. Spectral domain optical coherence tomography images were reviewed at each visit to determine the attachment of the posterior hyaloid. Best-corrected visual acuity and retinal thickness were also recorded. Outcomes at Months 2 and 6 were compared between the eyes with persistent vitreomacular attachment (Stage 1) and those with posterior vitreous detachment (Stages 2 or 3 PVD) at baseline. RESULTS: At baseline, 30 eyes had Stage 1 PVD and 63 eyes had either Stage 2 or 3 PVD. Although there was a trend for both greater visual acuity gains and reductions in retinal thickness for the eyes with Stages 2 or 3 PVD, this failed to reach significance. Baseline visual acuity and age were negatively associated with visual acuity change, and baseline retinal thickness alone was associated with retinal thickness change. CONCLUSION: Visual acuity, retinal thickness, and age at the baseline examination, but not PVD status, are associated with functional and anatomical outcomes after intravitreal aflibercept for neovascular age-related macular degeneration.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Doenças Retinianas/fisiopatologia , Acuidade Visual/fisiologia , Descolamento do Vítreo/fisiopatologia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Estudos Prospectivos , Retina/patologia , Aderências Teciduais/fisiopatologia , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Corpo Vítreo/fisiologia , Degeneração Macular Exsudativa/fisiopatologia
2.
J Biol Chem ; 287(23): 18872-87, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22493452

RESUMO

Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrP(C) (PrP(Sc)) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrP(Sc) to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrP(Sc) by stabilizing the conformation of PrP(C) or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrP(Sc) deposits.


Assuntos
Cerebelo/metabolismo , Fragmentos de Peptídeos/metabolismo , Polímeros/farmacologia , Proteínas PrPSc/metabolismo , Príons/metabolismo , Proteólise/efeitos dos fármacos , Tiofenos/farmacologia , Animais , Cerebelo/patologia , Camundongos , Proteínas PrPSc/patogenicidade , Príons/patogenicidade , Estabilidade Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína
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