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Daniel V Palanker, Seungbum Kang, Roopa Dalal, Yi Quan, Henri Lorach; Long-term Rescue of Photoreceptors in a Rodent Model of Retinitis Pigmentosa Associated with MERTK Gene Mutation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1005.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in MERTK gene decrease the capacity of retinal pigment epithelial (RPE) cells to phagocytize photoreceptor outer segments. This leads to accumulation of the outer segment debris in subretinal space, which separate photoreceptors from RPE, resulting in their degeneration and loss of vision. We investigated a possibility of delaying the photoreceptors degeneration by reducing the phagocytic load on RPE cells in an animal model having MERTK mutation.
In RCS rats, the animal model of retinitis pigmentosa due to MERTK mutation, we used two therapeutic approaches: (a) surgical clearance of subretinal debris when about half of photoreceptors remained, and (b) reduction of the photoreceptor density by photocoagulation. Subretinal lavage for debris removal was performed at P38, when about half of photoreceptors are still viable. Pattern laser photocoagulation was performed at P19, before the debris start to accumulate. To avoid scars, photoreceptors were coagulated with 50 µm laser spot size, which allows surrounding photoreceptors to shift into the lesions. Results were assessed functionally and morphologically, using electroretinography, optical coherence tomography, and histology during the 6-months follow-up.
Surgical removal of subretinal debris when about half of photoreceptors were still present, allowed a significant fraction of photoreceptors to survive up to 6 months, at least 3 times longer than in control eyes. Destruction of a fraction of photoreceptors by photocoagulation, which reduces the phagocytic load of the shed outer segments, also delayed the degeneration of the remaining photoreceptors. Benefits of both approaches were localized to the treated area, while the loss of photoreceptors continued to advance in untreated areas at the same pace as in control eyes.
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 function. 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 having diminished phagocytic capacity.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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