RESUMO
To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse. scAAV5 expressing RPE65 was injected subretinally into one eye of rd12 and Rpe65(-/-)::Rho(-/-) mice at postnatal day 14 (P14). Contralateral rd12 eyes were injected later, at P35. Rd12 behavioral testing revealed that rod vision loss was prevented with either P14 or P35 treatment, whereas cone vision was only detected after P14 treatment. Consistent with this observation, P35 treatment only restored rod electroretinogram (ERG) signals, a result likely due to reduced cone densities at this time point. For Rpe65(-/-)::Rho(-/-) mice in which there is no confounding rod contribution to the ERG signal, cone cells and cone-mediated ERGs were also maintained with treatment at P14. This work establishes that a self-complimentary AAV5 vector can restore substantial visual function in two genetically distinct models of Rpe65 deficiency within 4 days of treatment. In addition, this therapy prevents cone degeneration but only if administered before extensive cone degeneration, thus supporting continuation of current Leber's congenital amaurosis-2 clinical trials with an added emphasis on cone subtype analysis and early intervention.
Assuntos
Proteínas de Transporte/fisiologia , Dependovirus/genética , Proteínas do Olho/fisiologia , Terapia Genética , Atrofia Óptica Hereditária de Leber/terapia , Células Fotorreceptoras Retinianas Cones/fisiologia , Degeneração Retiniana/genética , Degeneração Retiniana/prevenção & controle , Animais , Modelos Animais de Doenças , Vetores Genéticos , Camundongos , cis-trans-IsomerasesRESUMO
Spontaneous infarction of physiologically hyperplastic breast tissue or of an adenoma-fibroadenoma presenting as breast mass during pregnancy or in the early postpartum period is a recognized but rare clinical pathologic entity. Only 24 such cases have been reported in the English language literature to our knowledge. We report four additional cases of breast infarction associated with pregnancy, review the literature, and discuss possible etiologies and pathogenesis of this uncommon event.
