OBJECTIVETo gain insight into the potential mechanism of mitochondria dysfunction in pathogenesis, progression and therapeutic management of glaucoma.

DATA SOURCESThe data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "mitochondria", "glaucoma" and "trabecular meshwork" or "retinal ganglion cells".

STUDY SELECTIONArticles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.

RESULTSMitochondrial dysfunction or injury was demonstrated in different eye tissue of glaucoma. A variety of potential injuries (light, toxic materials, oxidative injury, mechanical stress, aging, etc.) and the inherent DNA defects are deemed to cause mitochondrial structural and functional destruction in trabecular meshwork cells, retinal ganglion cells, etc. of glaucoma. In addition, various new experimental and therapeutic interventions were used to preserve mitochondrial function, which may be useful for protecting against optic nerve degeneration or reducing the death of retinal ganglion cells in glaucoma.

CONCLUSIONSMitochondria play an important role in the pathogenesis of glaucoma, various strategies targeting mitochondrial protection might provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage.

Glaucoma ; metabolism ; pathology ; Humans ; Mitochondria ; metabolism ; Retinal Ganglion Cells ; metabolism ; Trabecular Meshwork ; metabolism

The effects of suppression of CD44 by CD44-specific antisense oligonucleotide on attachment of human trabecular meshwork cells to hyaluronic acid (HA) were observed and the possible relationship between CD44 and primary open-angle glaucoma (POAG) investigated. CD44-specific antisense oligonucleotide was delivered with cationic lipid to cultured human trabecular meshwork cells. The expression of CD44 suppressed by CD44-specific antisense oligonucleotide was detected by RT-PCR and Western blotting. The effect of CD44 suppression by specific antisense oligonucleotide on attachment of trabecular meshwork cells to HA was measured by MTT assay. Results showed that expression of CD44 was suppressed by CD44-specific antisense oligonucleotide. Antisense oligonucleotide also suppressed the adhesion of human trabecular meshwork cells to HA in a concentration dependent manner. It was concluded that attachment of human trabecular meshwork cells to HA was decreased when CD44 was suppressed by specific antisense oligonucleotide. CD44 might play a role in pathogenesis of POAG by affecting the adhesion of trabecular meshwork cells to HA.
Cell Adhesion ; Cells, Cultured ; Glaucoma, Open-Angle ; metabolism ; pathology ; Humans ; Hyaluronan Receptors ; biosynthesis ; genetics ; Hyaluronic Acid ; metabolism ; Oligonucleotides, Antisense ; pharmacology ; Trabecular Meshwork ; cytology

PURPOSE: To investigate the correlation between peripheral anterior synechia (PAS) and the quantitative anterior chamber angle parameters measured by ultrasound microscopy (UBM) in angle-closure glaucoma suspect (ACGS) eyes. METHODS: Eyes were defined ACGS as having occludable angles and intraocular pressure less than 21 mm Hg without glaucomatous optic nerve head. The gonioscopic criteria for ACGS were the trabecular meshwork invisible in 3 or more quadrants of the entire angle and the angular width less than 20 degrees by Shaffer classification. Twenty-seven eyes of 20 patients underwent anterior chamber angle and ciliary body imaging with UBM. Angle opening distance (AOD500), angle recess area (ARA), trabecular-ciliary process distance (TCPD) and trabecular-iris angle (TIA) were measured from the UBM images at each quadrant. RESULTS: The AOD500, ARA, and TIA were not significantly different between the eyes with PAS (9 eyes) and without PAS (18 eyes) at each quadrant. However, the TCPD was significantly shorter in the superior quadrant when compared with the eyes without PAS (mean: 405.3+/-70.9 micrometer vs 536.4+/-140.5 micrometer) (p<0.05). CONCLUSIONS: The results suggest that the shorter distance from trabecular meshwork to ciliary body or the anterior placement of ciliary process may play a role in the development of PAS in ACGS eyes.
Aged ; Anterior Chamber/*ultrasonography ; Ciliary Body/pathology/ultrasonography ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Glaucoma, Angle-Closure/pathology/*ultrasonography ; Gonioscopy ; Humans ; Male ; Microscopy, Acoustic/*methods ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Trabecular Meshwork/pathology/ultrasonography

We report a case of recurrent occlusion of laser iridotomy (LI) sites after a Visian ICL (Implantable contact lens version 4, Staar Surgical AG, Nidau, Switzerland) implantation. A 45-year-old woman had bilateral ICL implantation after placement of two peripheral LI sites in each eye to prevent pupillary block. At one month after the operation, severe narrowing or occlusion of four LI sites occurred. After this, although she received four additional LIs at postoperative months 1, 6, 9 and 10 in both eyes, the narrowing or occlusion recurred. Mild chronic anterior chamber inflammation was observed intermittently throughout the follow-up period. We performed clear lens extraction in both eyes (at postoperative month 11 in the left eye and month 26 in the right eye) due to recurrent occlusion of the LI sites and excess trabecular meshwork pigment deposition presumably caused by the four repeated LIs. Recurrent obstruction of LI sites can occur after ICL implantation. These problems were unresolvable despite four repeated laser iridotomies. The risks associated with anterior uveitis must be considered when planning an ICL implantation.
Female ; Humans ; Iridectomy/*methods ; Iris/*surgery ; *Laser Therapy ; Lasers, Solid-State ; Lens Implantation, Intraocular/*adverse effects ; Middle Aged ; *Phakic Intraocular Lenses ; Pigment Epithelium of Eye/pathology ; *Postoperative Complications ; Recurrence ; Reoperation ; Trabecular Meshwork/pathology ; Uveitis, Anterior/etiology

PURPOSE: To investigate the effect of advanced glycation end products (AGE) on oxidative stress and cellular senescence in cultured human trabecular meshwork cells (HTMC). METHODS: Primarily cultured HTMC were exposed to 0, 10, 50, 100, 200 microg/mL of glycated bovine serum albumin (G-BSA) for 5 days. Also co-exposed were L-arginine, sepiapterin, and antioxidant N-acetylcysteine (NAC). Cellular survival and production of nitric oxide (NO), superoxide, and reactive oxygen species were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay, Griess assay, cytochrome c assay, and dichlorofluorescin diacetate assay, respectively. Senescence-associated beta-galactosidase staining was performed to quantify the degree of cellular senescence. RESULTS: G-BSA decreased cellular survival, NO production, and increased superoxide production significantly in a dose-dependent manner. The effects of G-BSA were abolished with co-exposure of L-arginine, sepiapterin, and NAC. G-BSA enhanced cellular senescence accompanied by increased production of reactive oxygen species. G-BSA-induced cellular senescence was suppressed by application of L-arginine, sepiapterin, and NAC. CONCLUSIONS: AGE enhances cellular senescence of HTMC accompanied with increased oxidative stress. AGE-induced oxidative stress and cellular senescence could be delayed by application of anti-oxidants.
Acetylcysteine/metabolism ; Apoptosis/drug effects/physiology ; Arginine/metabolism ; Cell Aging/drug effects/*physiology ; Cell Survival/drug effects/physiology ; Cells, Cultured ; Glycosylation End Products, Advanced/metabolism/*toxicity ; Humans ; Nitric Oxide/metabolism ; Oxidative Stress/*physiology ; Pterins/metabolism ; Reactive Oxygen Species/metabolism ; Serum Albumin, Bovine/metabolism/toxicity ; Trabecular Meshwork/drug effects/*metabolism/*pathology