RESUMO
PURPOSE: To compare intraocular vascular endothelial growth factor (VEGF) level in patients with and without Coats' disease, and to report a case of Coats' disease that responded to intravitreal injection of bevacizumab. METHODS: Intraocular fluid was obtained from four eyes with Coats' disease (subretinal fluid in three eyes and aqueous in one eye) and from five eyes with rhegmatogenous retinal detachment (subretinal fluid in four eyes and vitreous in one eye). Intraocular VEGF level was compared between these two groups. In one eye with stage 2B Coats' disease, macular edema, visual acuity, and intraocular VEGF level were compared before and after intravitreal injection of bevacizumab. RESULTS: Mean intraocular VEGF level in eyes with Coats' disease was 2,394.5 pg/ml, compared to 15.3 pg/ml in eyes with rhegmagenous retinal detachment. In the eye with stage 2B Coats' disease, macular edema was reduced after bevacizumab injection, and the visual acuity improved from 0.05 to 0.2. Intraocular VEGF level decreased from 1247 pg/ml to 20.4 pg/ml 1 month after the injection. CONCLUSION: Coats' disease is associated with increased intraocular VEGF level. Bevacizumab may be a valuable adjunctive treatment for Coats' disease.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Humor Aquoso/metabolismo , Líquidos Corporais/metabolismo , Doenças Retinianas/metabolismo , Telangiectasia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Bevacizumab , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Exsudatos e Transudatos , Feminino , Angiofluoresceinografia , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/metabolismo , Doenças Retinianas/tratamento farmacológico , Vasos Retinianos/patologia , Telangiectasia/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Corpo VítreoRESUMO
PURPOSE: Variants of complement factor H (Cfh) affecting short consensus repeats (SCRs) 6 to 8 increase the risk of age-related macular degeneration. Our aim was to explore the effect of expressing a Cfh variant on the in vivo susceptibility of the retina and RPE to oxidative stress and inflammation, using chimeric Cfh transgenic mice (chCfhTg). METHODS: The chCfhTg and age-matched C57BL/6J (B6) mice were subjected to oxidative stress by either normal aging, or by exposure to a combination of oral hydroquinone (0.8% HQ) and increased light. Eyes were collected for immunohistochemistry of RPE-choroid flat mounts and of retinal sections, ELISA, electron microscopy, and RPE/microglia gene expression analysis. RESULTS: Aging mice to 2 years led to an increased accumulation of basal laminar deposits, subretinal microglia/macrophages (MG/MΦ) staining for CD16 and for malondialdehyde (MDA), and MDA-modified proteins in the retina in chCfhTg compared to B6 mice. The chCfhTg mice maintained on HQ diet and increased light showed greater deposition of basal laminar deposits, more accumulation of fundus spots suggestive of MG/MΦ, and increased deposition of C3d in the sub-RPE space, compared to controls. In addition, chCfhTg mice demonstrated upregulation of NLRP3, IP-10, CD68, and TREM-2 in the RNA isolates from RPE/MG/MΦ. CONCLUSIONS: Expression of a Cfh transgene introducing a variant in SCRs 6 to 8 was sufficient to lead to increased retinal/RPE susceptibility to oxidative stress, a proinflammatory MG/MΦ phenotype, and a proinflammatory RPE/MG/MΦ gene expression profile in a transgenic mouse model. Our data suggest that altered interactions of Cfh with MDA-modified proteins may be relevant in explaining the effects of the Cfh variant.
Assuntos
Fator H do Complemento/genética , Microglia/citologia , Estresse Oxidativo/genética , Retina/metabolismo , Envelhecimento/fisiologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas de Transporte/metabolismo , Quimiocina CXCL10/metabolismo , Fator H do Complemento/fisiologia , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo/fisiologia , Receptores Imunológicos/metabolismo , Epitélio Pigmentado da Retina/metabolismoRESUMO
PURPOSE: To investigate the function of platelet-activating factor (PAF) in cultured retinal pigment epithelial (RPE) and choroidal endothelial (CE) cells. METHODS: The in vitro and in vivo expression of PAF-receptors (PAF-R) on both these cells was determined. The production of PAF by RPE cells was also determined. The effect of PAF on the proliferation, migration, permeability, and apoptosis of CE cells was examined, and the modulation of PAF on the VEGF level in RPE cells was assessed. RESULTS: PAF-R was present in both types of cells in vitro, as well as in RPE and choroid in vivo. Cultured RPE cells synthesized PAF. PAF stimulated CE cell migration and permeability but not the proliferation. PAF also increased the VEGF level in RPE cells. CONCLUSIONS: Similar to VEGF, PAF stimulates CE cell migration and permeability. It also up-regulates VEGF level in RPE cells. PAF may be involved in the pathogenesis of choroidal neovascularization.