Abstract
BackgroundOpen-angle glaucoma appears to be induced by the malfunction of the trabecular meshwork cells due to injury induced by oxidative damage and mitochondrial impairment. Here, we report that, in fact, we have detected mitochondrial damage only in primary open-angle glaucoma and pseudo-exfoliation glaucoma, among several glaucoma types compared.Methodology/Principal FindingsMitochondrial damage was evaluated by analyzing the common mitochondrial DNA deletion by real-time PCR in trabecular meshwork specimens collected at surgery from glaucomatous patients and controls. Glaucomatous patients included 38 patients affected by various glaucoma types: primary open-angle, pigmented, juvenile, congenital, pseudoexfoliative, acute, neovascular, and chronic closed-angle glaucoma. As control samples, we used 16 specimens collected from glaucoma-free corneal donors. Only primary open-angle glaucoma (3.0-fold) and pseudoexfoliative glaucoma (6.3-fold) showed significant increases in the amount of mitochondrial DNA deletion. In all other cases, deletion was similar to controls.Conclusions/SignificanceDespite the fact that the trabecular meshwork is the most important tissue in the physiopathology of aqueous humor outflow in all glaucoma types, the present study provides new information regarding basic physiopathology of this tissue: only in primary open-angle and pseudoexfoliative glaucomas oxidative damage arising from mitochondrial failure play a role in the functional decay of trabecular meshwork.
Highlights
Glaucoma is a neurodegenerative eye disease, the affected regions of which are (a) the retina, the optic nerve; (b) the central nervous system, especially the lateral geniculate nucleus of the brain [1]; and (c) the eye anterior chamber, the trabecular meshwork (TM)
A variety of parameters reflecting the occurrence of molecular alterations in mitochondria were considered, including (a) %mitochondrial DNA (mtDNA) deletion/mtDNA, which is the amount of deleted mtDNA compared to total mtDNA and directly expresses the extent of the 4977 mtDNA common lesion; (b) total mtDNA/mg wet tissue, which represents the amount of mitochondria in the analyzed TM biopsy; (c) total nDNA/mg wet tissue, which represents the number of cells in the analyzed TM biopsy
Our results indicate that mitochondrial damage and related oxidative stress occur in primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG) and not in other glaucoma types
Summary
Glaucoma is a neurodegenerative eye disease, the affected regions of which are (a) the retina, the optic nerve; (b) the central nervous system, especially the lateral geniculate nucleus of the brain [1]; and (c) the eye anterior chamber, the trabecular meshwork (TM). Free radicals and reactive oxygen species are able to affect the cellularity of the human TM (HTM) These findings suggest that an intraocular pressure increase, which characterizes most glaucomas, is related to oxidative and degenerative processes affecting the HTM and, its endothelial cells [7]. Damage accruing to the mitochondrial genome is associated with increased cellular stress and organelle dysfunction [17] He and colleagues showed that TM cells of patients with POAG undergo ATP diminution, as their functionality is endangered by an intrinsic mitochondrial complex I defect, causing a respiratory chain deficit in these cells [18]. The amount of nuclear DNA in relation to wet tissue weight is decreased [14] These findings provide evidence that mitochondrial damage is severe in the TM of POAG patients. We report that, we have detected mitochondrial damage only in primary open-angle glaucoma and pseudo-exfoliation glaucoma, among several glaucoma types compared
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