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P.T. Johnson, M.N. Brown; Synaptic Protein Expression is Compromised in Photoreceptors Overlying Drusen . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1815.
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Purpose: Drusen are extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane. Numerous and/or confluent drusen are a significant risk factor for age–related macular degeneration. Drusen are also associated with cellular and molecular abnormalities in overlying photoreceptor cells, including the redistribution of opsin in rod photoreceptors and the deflection and shortening of rod and cone inner and outer segments. The purpose of this study is to investigate the impact of drusen on the expression of synaptic proteins in overlying photoreceptor cells. Methods: Retina and RPE/choroid were dissected from human donor eyes, embedded in agarose and sectioned at 100µm using a vibratome. Tissue sections were immunostained with antibodies against synaptic proteins and processed for confocal immunofluorescence microscopy. Drusen were identified by immunostaining with antibodies against apolipoprotein E. Results: In normal retina, antibodies directed against the synaptic proteins synaptophysin, synaptotagmin, SV2, syntaxin 3, SNAP–25, and synaptobrevin, intensely label rod and cone photoreceptor terminals within the outer plexiform layer (OPL). Small, round rod terminals and larger, more elongated cone terminals form a thick plexus approximately 2–3 terminals thick in the outer portion of the OPL. Over drusen, however, labeling of rod and cone synaptic terminals in the OPL is markedly reduced. All 6 synaptic proteins exhibit a sharp decline in labeling intensity and in the number of labeled terminals. Regions of the OPL that are completely devoid of rod and cone terminals are frequently observed over drusen, even over small, sub–clinical drusen (< 63um). The loss of synapse–related immunoreactivity in photoreceptor terminals occurs only directly over drusen, whereas adjacent regions of the OPL exhibit normal synaptic terminal labeling. Conclusions: These data indicate that photoreceptors overlying drusen undergo a significant decrease in synaptic protein expression. Such decreases suggest that photoreceptor cells overlying drusen may be dysfunctional and may provide an explanation for the focal changes in visual acuity and sensitivity that are often found in retinal regions with high drusen loads.
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