scispace - formally typeset
Search or ask a question
Topic

Optic Disk Drusen

About: Optic Disk Drusen is a research topic. Over the lifetime, 150 publications have been published within this topic receiving 6268 citations.


Papers
More filters
Journal ArticleDOI
TL;DR: Data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation.
Abstract: Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch's membrane and are risk factors for developing age-related macular degeneration (AMD). The progression of AMD might be slowed or halted if the formation of drusen could be modulated. To work toward a molecular understanding of drusen formation, we have developed a method for isolating microgram quantities of drusen and Bruch's membrane for proteome analysis. Liquid chromatography tandem MS analyses of drusen preparations from 18 normal donors and five AMD donors identified 129 proteins. Immunocytochemical studies have thus far localized ≈16% of these proteins in drusen. Tissue metalloproteinase inhibitor 3, clusterin, vitronectin, and serum albumin were the most common proteins observed in normal donor drusen whereas crystallin was detected more frequently in AMD donor drusen. Up to 65% of the proteins identified were found in drusen from both AMD and normal donors. However, oxidative protein modifications were also observed, including apparent crosslinked species of tissue metalloproteinase inhibitor 3 and vitronectin, and carboxyethyl pyrrole protein adducts. Carboxyethyl pyrrole adducts are uniquely generated from the oxidation of docosahexaenoate-containing lipids. By Western analysis they were found to be more abundant in AMD than in normal Bruch's membrane and were found associated with drusen proteins. Carboxymethyl lysine, another oxidative modification, was also detected in drusen. These data strongly support the hypothesis that oxidative injury contributes to the pathogenesis of AMD and suggest that oxidative protein modifications may have a critical role in drusen formation.

1,159 citations

Journal ArticleDOI
TL;DR: It is shown that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans, and these findings provide evidence for the free radical theory of aging.
Abstract: Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1−/− mice of different ages showed that the older animals had drusen, thickened Bruch’s membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1−/− mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1−/− mice showed oxidative damage, and their β-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1−/− mouse is a valuable animal model to study human age-related macular degeneration.

406 citations

Journal ArticleDOI
TL;DR: It is shown that drusen isolated from donor AMD eyes activates the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, causing secretion of interleukin-1β (IL-1 β) and IL-18, which indicates a protective role for NLRP3 andIL-18 in the progression of AMD.
Abstract: Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Drusen accumulation is the major pathological hallmark common to both dry and wet AMD. Although activation of the immune system has been implicated in disease progression, the pathways involved are unclear. Here we show that drusen isolated from donor AMD eyes activates the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, causing secretion of interleukin-1b (IL-1b) and IL-18. Drusen component C1Q also activates the NLRP3 inflammasome. Moreover, the oxidative-stress-related protein-modification carboxyethylpyrrole (CEP), a biomarker of AMD, primes the inflammasome. We found cleaved caspase-1 and NLRP3 in activated macrophages in the retinas of mice immunized with CEP-adducted mouse serum albumin, modeling a dry-AMD–like pathology. We show that laser-induced choroidal neovascularization (CNV), a mouse model of wet AMD, is exacerbated in Nlrp3(-/-) but not Il1r1(-/-) mice, directly implicating IL-18 in the regulation of CNV development. These findings indicate a protective role for NLRP3 and IL-18 in the progression of AMD.

366 citations

Journal ArticleDOI
TL;DR: It is most important to differentiate optic disk drusen from papilledema in order to avoid unnecessary neurological examinations, but also to avoid overlooking genuine neurologic disorders.

276 citations

Journal ArticleDOI
TL;DR: The findings of a clinicopathologic correlative study of 18 cases of drusen are definitely related to axonal degeneration of the optic nervehead and the first ultrastructural study of this disease in the literature are reported.

214 citations

Network Information
Related Topics (5)
Retinal pigment epithelium
9.2K papers, 318.1K citations
77% related
Visual acuity
32K papers, 797.1K citations
77% related
Retinal
24.4K papers, 718.9K citations
77% related
Retinopathy
12.8K papers, 431.9K citations
76% related
Diabetic retinopathy
18.7K papers, 537.2K citations
75% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20214
20201
20191
20183
20179
201616