RESUMEN
Purpose: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization. Methods: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed. Results: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss. Conclusions: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.
Asunto(s)
Oxígeno , Neovascularización Retiniana , Retinopatía de la Prematuridad , Animales , Humanos , Ratones , Animales Recién Nacidos , Modelos Animales de Enfermedad , Hiperoxia/complicaciones , Inyecciones Intravítreas , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Ratones Endogámicos C57BL , Oxígeno/toxicidad , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/prevención & control , Neovascularización Retiniana/patología , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND AND AIM: Although intentional replantation for extraoral treatment is a solution for complicated endodontic cases, it is accompanied with risk of root resorption which is most likely due to extraction trauma and infected remnants. Laser therapies have long been proved for bactericidal and biostimulation effects. In the present case, a pulpitis combined severe periodontal destruction molar was extracted with an Er:YAG laser for thorough degranulation and disinfection. Before the extraction and right after the treatment, low level laser therapy (LLLT) with 810nm diode was applied for biostimulation. RESULT: Patient reported no post operative pain after laser treatment. Clinical follow-up showed uneventful healing, and excellent bone regeneration. CONCLUSION: The Er:YAG laser coupled with low level laser therapy (810 nm diode) has shown to assist and improve intentional replantation in disinfection procedure, and it may preserve more vital cells and enhance bioregeneration for less operative pain and better healing.