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Emily Plyler, Matthew A Smith, Jason R Richardson, Christine M Dengler-Crish, Samuel D Crish; Retinal amyloid pathology requires CD36 receptors.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3720.
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Accumulation and aggregation of amyloid-beta, a neurotoxic protein associated with Alzheimer’s disease (AD), has been identified in retinas of glaucoma, age-related macular degeneration, and diabetic retinopathy. Moreover, the retina and optic nerve have been implicated as some of the earliest sites of pathology in AD, exhibiting amyloidosis prior to degeneration of the hippocampus and entorhinal cortex. However, the mechanism of amyloid deposition is not clear. Here, we sought to determine the potential role for cluster of differentiation 36 (CD36) on amyloid deposition and neuroinflammation in the retina and its projection.
Fibrillar, fluorophore-tagged amyloid-beta was unilaterally injected into the vitreal chamber of 6-8 month old C57BL/6J mice and transgenic mice lacking CD36. One or two weeks following injection, retinas, optic nerves, and their brain targets were evaluated by immunofluorescence and multiplex protein quantitation for inflammatory and neurodegenerative markers.
Amyloid-beta produced neuroinflammation throughout the entire retinal projection - including distal brain targets. Retinal ganglion cell (RGC) degeneration was evident, with significant RGC reductions at 1 (77% of control) and 2 weeks (46% of control) after injection. Surprisingly, amyloid pathology was sectorial and spread to the opposite, un-injected retina and projection -- resulting in inflammation and RGC loss in the untreated eye. Amyloid-beta fibril injections in CD36-null mice did not produce significant neuroinflammatory responses or RGC loss.
Amyloid-beta fibrils produce spreading, sectorial inflammation and neurodegeneration in the absence of other stress factors in the retina and its projection. CD36 is necessary for amyloid-mediated neuroinflammation and acute degeneration.
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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