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목적 : MERTK gene mutation decreases the capacity of RPE cells to phagocytize photoreceptor (PR) outer segments, which leads to the accumulation of outer segments and the formation of debris in subretinal space. Debris layer separates PR from RPE cell layer, resulting in their degeneration. We investigated whether it is possible to delay the degeneration of PR by reducing phagocytic loads on RPE cells in an animal model with MERTK mutation. Two therapeutic approaches were used for the study: (a) surgical clearance of subretinal debris, (b) reduction of PR density by by photocoagulation.
방법 : RCS rats, an animal model of retinitis pigmentosa due to MERTK mutation, were used for two different approaches. Subretinal lavage for debris removal was performed at P38, when about half of photoreceptors are still viable, and pattern laser photocoagulation was performed at P19, before the debris starts to accumulate. To avoid laser scar, barely visible burns were created with only 50 µm-laser spot size, which allows surrounding photoreceptors to shift into the laser ablated lesions. RCS rats were followed-up until 6 months. Treated eyes were assessed functionally and morphologically.
결과 : Surgical debris removal allowed remaining photoreceptors to survive up to 6 months, which survived 3 times longer than control eyes. Destruction of a fraction of photoreceptors by photocoagulation, which reduces the phagocytic load of the shed outer segment, also delayed the degeneration of remaining photoreceptors. Benefits of both approaches were localized to only treated area, while the loss of photoreceptors continued to progress in untreated area at the same pace as in control eyes.
결론 : MERTK-related form of inherited retinal degeneration, which has currently no cure, could be amenable to subretinal surgery or laser therapy with the purpose of extending visual functions. The long-term preservation of photoreceptors with both therapies may be associated with balancing the supply and demand in recycling of the outer segments by RPE cells with diminished phagocytic capacity.
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