Sirt1 Involvement in rd10 Mouse Retinal Degeneration

Abstract

The results suggest a link between Sirt1 production and retinal degeneration in rd10 mice. The anti-apoptotic, neuroprotective role of Sirt1 in the mouse retina is based on the involvement of Sirt1 in double DNA strand-break repair mechanisms and in maintaining energy homeostasis in photoreceptor cells. The results suggest that the neuroprotective properties of Sirt1 may gradually weaken in rd10 mouse photoreceptor cells.

The Expression of SIRT1 in Ocular Tissues

“…Significant SIRT1 immunolabeling was observed in the nuclei and cytoplasm of corneal epithelial cells, and SIRT1 was also detected in the nuclei of flattened corneal endothelial cells and in keratocytes. However, no SIRT1 was detected in the acellular part of the corneal stroma [24]. In the ciliary body, SIRT1 was found mainly in the nuclei of ciliary process cells, also in the pigmented and nonpigmented ciliary epithelial cell layers.…”

“…SIRT1 immunolabeling was detected in the RPE and melanocyte nuclei, while mostly in the cytoplasm of choroidal vessels endothelial cells. The retinal distribution of SIRT1 was exclusively observed in the nucleus of the ONL, INL, and GCL and was never detected in the cytoplasm [24]. Another study reported by Maloney et al [26] has shown different evidences of the SIRT1 expression in the retina.…”

“…Jaliffa et al [24] provided evidences at the first time of the details of SIRT1 mRNA and protein levels and distributions in normal adult mouse eyes. They detected SIRT1 mRNA by RT-PCR in the neuroretina, Retinal Pigment Epithelium (RPE), ciliary body, and lens.…”

Evaluation of Sirtuin Role in Neuroprotection of Retinal Ganglion Cells in Hypoxia

“…[5][6][7] SIRT1's deacetylation of histone proteins modulates nonhistone substrates that play an essential role in neuronal cell survival during oxidative stress and apoptotic states. 8 SIRT1 induces a number of transcription factors/proteins such as p53, 9 FOXO (Forkhead box), PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), NF-jB (nuclear factor-jB), 10,11 VEGF, and EPO (erythropoietin).…”

“…12 In the eye, SIRT1 is expressed in various retinal cells, such as the retinal pigment epithelium (RPE), choroid, and neural retina. 7 In several disease models, SIRT1 activation led to the cessation of dysfunction and damage to RGCs. In an experimental model of optic neuritis, Shindler et al 13 showed that intravitreal injection of SIRT1 activators established a beneficial effect to RGC survival by attenuating RGC death.…”