Glaucoma is characterized by progressive
loss of retinal ganglion cells (RGCs).
The loss of RGCs also occurs as an
age-dependent process.
Several regulatory factors, that could
impact glaucoma and aging, have been studied in animal models.
Sirtuins (Sirts) belong to a widely preserved
protein family.
They resemble the yeast Sir2 protein, which
operates as a NAD-dependent histone deacetylase, prolonging the yeast’s lifespan.
The anti-aging protein, Sirt6, is highly
expressed in RGCs.
It is essential in protecting RGCs from the
effects of aging and glaucoma.
In mouse models of high-tension glaucoma, the
Sirt6 level was decreased after IOP elevation.
Deleting Sirt6 globally or specifically in
RGCs led to progressive RGC loss and optic nerve degeneration during aging,
despite normal intraocular pressure (IOP), resembling a phenotype of
normal-tension glaucoma.
Genetic overexpression of Sirt6 globally or
specifically in RGCs significantly attenuated high tension-induced degeneration
of RGCs and their axons.
The study shows the critical role of Sirt6
in preventing RGC and optic nerve degeneration during aging and glaucoma.
Wenbo Zhang, a co-author and Professor of
Ophthalmology at the University of Texas, was quoted as saying "Therapeutically
targeting Sirt6 offers a promising new avenue for glaucoma treatment,
especially for cases that do not respond to traditional treatments aimed at
reducing eye pressure". He added, "This could be a game-changer in
how we approach this disease."
REFERENCE:
Xia F, Shi S, Palacios E, Liu W, Buscho SE,
Li J, Huang S, Vizzeri G, Dong XC, Motamedi M, Zhang W, Liu H. Sirt6 protects
retinal ganglion cells and optic nerve from degeneration during aging and
glaucoma. Mol Ther. 2024 Jun 5;32(6):1760-1778. doi: 10.1016/j.ymthe.2024.04.030.
Epub 2024 Apr 24. PMID: 38659223; PMCID: PMC11184404.
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