HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Johnson, P. T. Articles by Johnson, L. V. Search for Related Content PubMed PubMed Citation Articles by Johnson, P. T. Articles by Johnson, L. V.

Synaptic Pathology, Altered Gene Expression, and Degeneration in Photoreceptors Impacted by Drusen

From the Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, California.

PURPOSE. Drusen are risk factors for age-related macular degeneration and have been shown to negatively impact cells of the RPE and retina. In this study, the effects of drusen on the synaptic machinery of retinal photoreceptors are investigated.

METHODS. Human donor eye tissue containing retina, RPE, and choroid was processed for confocal immunofluorescence microscopy, laser capture microdissection, and light and electron microscopy. Tissue sections were immunostained with a panel of antibodies to synapse-associated proteins. Populations of photoreceptors over drusen and normal populations of photoreceptors were microdissected from fresh frozen tissue, RNA was purified, and quantitative PCR was performed to compare relative levels of gene expression.

RESULTS. The number of photoreceptor synaptic terminals is reduced in regions of the outer plexiform layer over drusen, synaptic proteins are mislocalized in photoreceptor cells, and synaptic terminals are often observed within the outer nuclear layer. Photoreceptors over drusen also increase expression of the stress response proteins apolipoprotein E and B-crystallin. Abnormal immunolabeling patterns are not restricted to photoreceptors directly over drusen but are also observed in cells flanking drusen. Gene expression analysis confirms reductions in the expression of genes coding for synapse-associated proteins and signal transduction proteins and increases in the expression of apolipoprotein E and B-crystallingene transcripts. Ultrastructural analysis of photoreceptor synaptic terminals over drusen reveals significant abnormalities, and cell counts show a reduction in photoreceptor density directly over, and lateral to, drusen of all sizes.

CONCLUSIONS. Photoreceptors overlying and flanking drusen exhibit morphologic and biochemical signs of degeneration. The expression of synapse-associated proteins decreases in photoreceptor synaptic terminals, whereas the expression of stress-response proteins increases. Reductions in photoreceptor cell densities over, and flanking, drusen suggest that these degenerative effects eventually result in the death of photoreceptors.

This article has been cited by other articles:

				E. Midena, S. Vujosevic, E. Convento, A. Manfre', F. Cavarzeran, and E. Pilotto Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration Br. J. Ophthalmol., November 1, 2007; 91(11): 1499 - 1503. [Abstract] [Full Text] [PDF]

				P. T. Johnson, K. E. Betts, M. J. Radeke, G. S. Hageman, D. H. Anderson, and L. V. Johnson Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid PNAS, November 14, 2006; 103(46): 17456 - 17461. [Abstract] [Full Text] [PDF]

				O. Sunnotel, W. J. Snelling, L. Xiao, K. Moule, J. E. Moore, B. C. Millar, J. S. G. Dooley, and C. J. Lowery Rapid and sensitive detection of single cryptosporidium oocysts from archived glass slides. J. Clin. Microbiol., September 1, 2006; 44(9): 3285 - 3291. [Abstract] [Full Text] [PDF]