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Elizabeth Couser, Steven L Bernstein, Michaela Kunz Mathews; Effect of Alzheimer's Disease on Melanopsin Expression in the Lateral Geniculate Nucleus. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5561.
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While retinas from individuals with Alzheimer’s disease (AD) undergo degenerative changes, the effects of AD on the midbrain connecting eye and cortex are understudied. AD patients also experience a loss of melanopsin-containing retinal ganglion cells (mRGCs).We wanted to examine whether AD affects melanopsin expression in the lateral geniculate nucleus (LGN). We hypothesized that since AD affects RGCs, there should be a gradual loss of melanopsin expression as AD progresses. This information is essential in understanding the influence of AD on the central visual pathway.
Following IRB approval, we obtained human tissue samples from the Maryland Brain & Tissue Bank, which included age-matched normal, pre-clinical AD, and severe AD. We evaluated human LGN for the expression of melanopsin, as well as the number of normal neuron nuclei, using immunohistochemistry and confocal microscopy. Antibodies used were: anti-melanopsin (Thermo Scientific) and Brn3a (AbCam). Slides were analyzed using FluoviewSoftware.
Normal LGN tissue from age-matched controls showed abundant melanopsin expression in discrete deposits. In the parvocellular layer, Brn3a expression was abundant in small nuclei that were scattered throughout the section. Magnocellular layers showed many Brn3a(+) nuclei as well. In tissue from the preclinical and severely affected donors, there was a progressive decrease in the BRN3a marker in the LGN through the different stages of AD severity. Interestingly, while there was no reduction in melanopsin signal in the preclinical patients, this protein was drastically decreased in severe AD samples. Melanopsin was also seen to accumulate as smaller deposits in severe AD.
Similar to the retina and cortex, the LGN portion of the thalamic midbrain shows AD-related alterations, including melanopsin projections. AD also affects the number of LGN-Brn3a(+) neurons. The LGN-melanopsin signal appears to be preserved in pre-clinical AD. Since we previously showed that the LGN exhibits a progressive increase in inflammatory markers in AD, our current data supports a model whereby selective AD-related changes occur pre-clinically, but a threshold damage level is needed to affect melanopsin expression in the tissue samples. The impact of AD on the LGN including the progressive loss of magno and parvo neurons and melanopsin may further assist in explaining the visual deficits in early AD.
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