Purchase this article with an account.
K. A. Bodkin, S. C. Maloney, S. Bakalian, G. Novais, J. Isenberg, M. N. Burnier, Jr.; The Development of Choroidal Neovascular Membranes in Patients With AMD Is a SIRT1-Independent Process. Invest. Ophthalmol. Vis. Sci. 2009;50(13):952.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
SIRT1 is a potent deacetylase that regulates the expression of genes involved in homeostasis maintenance in the vascular system including NFkB and p53. Furthermore, SIRT1 plays a role in promoting angiogenesis in pathological processes such as neoplastic and vascular lesions. Experiments with animal models have shown that SIRT1 is necessary for proper vascular growth and retinal development. Choroidal neovascular (CNV) membranes are a hallmark of wet age-related macular degeneration (AMD) and are responsible for vision loss in 90% of patients. The aim of this study is to examine SIRT1 expression in human CNV membranes.
Formalin-fixed, paraffin-embedded sections of choroidal neovascular membranes excised from 17 patients with wet AMD were used in this study. Sections were subjected to immunohistochemistry using a polyclonal anti-SIRT1 antibody (dilution 1:50). Immunostaining was classified as either negative or positive in retinal pigment epithelial (RPE) cells, vascular endothelial cells, and fibroblasts. Additionally, four eyes from two female donors - aged 17 and 90 - were obtained from the Eye Bank of Canada and were also immunostained for SIRT1 expression. These eyes were used as controls and were compared to the AMD cases.
All of the 17 choroidal neovascular membranes were negative for SIRT1 expression in the cell types assessed. The staining pattern of control eyes was consistent between left and right eyes of each donor as well as between the two donors. None of the four control eyes revealed expression of SIRT1 in the retina, RPE, or iris while all eyes showed some SIRT1 positive melanocytes in the choroid as well as in the non-pigmented epithelial cells of the ciliary body. For the control eyes derived from the 90 year-old donor, SIRT1 was positive in the limbus as well as in the corneal epithelium, while these structures were absent from the material obtained from the 17 year-old donor.
The absence of SIRT1 expression in the CNV membranes suggests that SIRT1 may not play a role in the development of choroidal neovascularization. These results are in stark contrast to other forms of neovascularization in other organs in which SIRT1 plays a significant role. This negative result is important to illustrate that the neovascularization of this degenerative process (AMD) may have a different pathway from other forms of neovascularization. The possibility of other sirtuin proteins regulating choroidal neovascularization should be investigated further.
This PDF is available to Subscribers Only