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Marisol Corral-Debrinsky, Helene Cwerman-Thibault, Sébastien Augustin, Christophe Lechauve, Delphine Roussel, Elodie Reboussin, Ammara Mohammad, Anne Maron, Thomas Debeir; Correlation between mitochondrial dysfunction in DBA/2J mouse retinas and optic nerves and the progression of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4951.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is the second leading cause of blindness in the world characterized by the degeneration of retinal ganglion cells (RGCs) and optic nerve atrophy. Our aim is to provide insight into the potential involvement of mitochondrial impairment in the apparition and progression of the glaucomatous phenotype in DBA/2J mice.
The DBA/2J and C57BL/6J mice were subjected to exhaustive ocular evaluation during aging (from 2 to 15 month old) : IOP measurements, Slit-Lamp examination, in vivo confocal microscopy analysis, light-adapted electroretinogram (ERG) and flash-visual evoked potential (F-VEP) response recording, retinal and optic nerve (ON) histology, mRNA and protein abundance studies and respiratory chain enzymatic assays in retinas and optic nerves.
DBA/2J mice are characterized by: (1) iris fragmentation at 3-4 months of age, (2) increased IOP in 7 month-old mice remaining significantly high until the age of 12 months; (3) RGC loss (around -35% ) in mice at the age of 10-15 months compared with 2 month-old DBA/2J mice or age-matched C57BL/6J control mice; (4) Glial activation in ONs preceded RGC axon disappearance; (5) DBA/2J mice from 2 to 12 months displayed impaired F-VEP recordings which were considerably reduced in right and left visual cortices when compared to 2 month-old C57BL/6J mice. We found a consistent decrease on respiratory chain complex I, III and IV activities in retinas and optic nerves, which begins in 5 month-old mice demonstrating that mitochondrial dysfunction precedes the significant development of optic atrophy in DBA/2J mice. Moreover, 12 month-old DBA/2J mice exhibit 50% decrease in the steady-state levels of different mitochondrial proteins relative to 2 month-old mice confirming that mitochondrial dysfunction and energy depletion could contribute to the pathophysiological cascade leading to RGC loss and optic atrophy in DBA/2J mice.
The early respiratory chain defects and the overall mitochondrial dysfunction leading to energy depletion noticed in DBA/2J mice should render RGCs more sensitive to degeneration and certainly account for the initiation of glaucoma.
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