RESUMO
MERTK mutation reduces the ability of retinal pigment epithelial (RPE) cells to phagocytize the photoreceptor outer segments, which leads to accumulation of debris separating photoreceptors from RPE cells, resulting in their degeneration and loss of vision. In a rat model of Retinitis Pigmentosa due to MERTK mutation, we demonstrate that surgical removal of debris performed when about half of photoreceptors are lost (P38), allows the remaining photoreceptor cells to renew their outer segments and survive for at least 6 months - 3 times longer than in untreated eyes. In another set of experiments, patterned laser photocoagulation was performed before the debris formation (P19-25) to destroy a fraction of photoreceptors and thereby reduce the phagocytic load of shed outer segment fragments. This treatment also delayed the degeneration of the remaining photoreceptors. Both approaches were assessed functionally and morphologically, using electroretinography, optical coherence tomography, and histology. The long-term preservation of photoreceptors we observed indicates that MERTK-related form of inherited retinal degeneration, which has currently no cure, could be amenable to laser therapy or subretinal surgery, to extend the visual function, potentially for life.
Assuntos
Células Fotorreceptoras/patologia , Degeneração Retiniana/terapia , Retinose Pigmentar/terapia , c-Mer Tirosina Quinase/genética , Animais , Modelos Animais de Doenças , Eletrorretinografia , Células Epiteliais/patologia , Humanos , Fotocoagulação , Mutação , Procedimentos Cirúrgicos Oftalmológicos , Fagocitose/genética , Ratos , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Retinose Pigmentar/genética , Retinose Pigmentar/fisiopatologia , Tomografia de Coerência ÓpticaRESUMO
Photovoltaic restoration of sight requires intense near-infrared light to effectively stimulate retinal neurons. We assess the retinal safety of such radiation with and without the retinal implant. Retinal damage threshold was determined in pigmented rabbits exposed to 880nm laser radiation. The 50% probability (ED50) of retinal damage during 100s exposures with 1.2mm diameter beam occurred at 175mW, corresponding to a modeled temperature rise of 12.5°C. With the implant, the same temperature was reached at 78mW, close to the experimental ED50 of 71mW. In typical use conditions, the retinal temperature rise is not expected to exceed 0.43°C, well within the safety limits for chronic use.