Purchase this article with an account.
J. P. Fernandez de Castro, R. F. Mullins, J. Hernandez, M. H. Kuehn; Elevated Deposition of Lipofuscin in Glaucomatous Optic Nerves. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6116.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Lipofuscin accumulation has been observed in a number of neurodegenerative diseases. We recently found that autofluorescent particles also occur in the aged optic nerve. In this study we sought to analyze the nature of these particles and their correlation with aging, age-related macular degeneration and glaucoma.
Eight optic nerves from patients diagnosed with open angle glaucoma, ten with age-related macular degeneration, ten age-matched controls and five controls younger than 42 years were used for the study. All samples were fixed in paraformaldehyde, embedded in sucrose and frozen sections were prepared. Sections were analyzed with fluorescent microscopy, bright field microscopy, Sudan black staining and spectrofluorometry using a confocal laser scanning microscope. Sections were photographed and analyzed to establish the distribution, quantity, and size of the autofluorescent particles.
Granules fluoresced when excited at all tested wavelengths (421 to 724 nm with 9.8 nm intervals) and were distributed throughout the axonal columns but not in the septa. On unstained sections under light microscopy the granules were detectable but not prominent. The granules were markedly sudanophilic and lost their fluorescence after staining with Sudan black. The glaucoma group exhibited a higher density of granules than the age-matched controls (p-value=0.027). The average number of granules per square millimeter was 1136 in the glaucoma group, 943 in the controls, 907 in the AMD group, and 76 in the young control group. The average size of each particle was 15% higher in glaucoma samples and consequently the total autofluorescent area of this group was 57% larger than that of the AMD group (p=0.001). Spectrofluorometry revealed that the fluorescent properties are similar in diseased and healthy nerves, with highest emission when excited at 563 nm.
The histologic properties of the granules seen in the optic nerve sections correspond to lipofuscin aggregates, a result of incomplete degradation of oxidized proteins. The emission peak at 563 nm is analogous with the one found in the RPE, suggesting that their compositions are similar. The granules are more abundant in glaucoma which could indicate a higher level of oxidative stress in the glaucomatous optic nerve.
This PDF is available to Subscribers Only