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

PURPOSE: Transforming growth factor-beta2 is known to be present at elevated levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and diabetes but not in uveitis-related secondary glaucoma. We investigated total TGF-beta2 levels and levels of the active form of TGF-beta2 in the aqueous humor of eyes with different types of glaucoma. METHODS: The concentration of the total and active form of TGF-beta2 was measured in 63 patients with primary open angle glaucoma, neovascular glaucoma complicated with diabetes (NVG), and secondary open angle glaucoma complicated with uveitis (SOAG) using a double antibody 'sandwich-indirect' ELISA method. RESULTS: The levels of total TGF-beta2 in the aqueous samples of POAG, NVG, and SOAG were elevated. The levels of active TGF-beta2 in the aqueous samples of POAG, and NVG were also elevated, whereas the level of active TGF-beta2 was within the normal range in the aqueous samples of SOAG. CONCLUSIONS: These results suggest that the level of TGF-beta2 may play a role in the pathology of various types of glaucoma.
Uveitis/*metabolism ; Transforming Growth Factor beta/*metabolism ; Severity of Illness Index ; Middle Aged ; Humans ; Glaucoma, Open-Angle/*metabolism ; Glaucoma, Angle-Closure/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Diabetic Retinopathy/*metabolism ; Biological Markers/metabolism ; Aqueous Humor/*metabolism ; Aged, 80 and over ; Aged ; Adult

BACKGROUNDGlaucoma, an irreversible optic nerve neuropathy, always results in blindness. This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization (EVC) model by multiple in vivo and in vitro evidences.

METHODSWistar rat was used in this study. The elevated intraocular pressure (IOP) was induced by cauterization of three episcleral veins. IOP was monitored with Tono-Pen XL tonometer. Time-dependent changes to the neuronal retinal layers were quantified by Fourier domain-optical coherence tomography. The function of retina was evaluated by electroretinogram (ERG). Survival of retinal ganglion cells (RGCs) was quantified by retrograde labeling. Histology study was performed with retinal sections stained with hematoxylin-eosin, glial fibrillary acidic protein, and neuronal nuclear antigen. Retina and aqueous humor protein were extracted and cytotoxic protein tumor necrosis factor alpha (TNF-α) and alpha-2 macroglobulin (α2m) were measured with Western blotting.

RESULTSEVC is a relatively facile intervention, with low failure rates (<5%). After surgical intervention, chronic mild IOP elevation (about 1.6-fold over normal, P < 0.05) was induced for at least 6 weeks without requiring a second intervention. High IOP causes chronic and progressive loss of RGCs (averaging about 4% per week), progressive thinning of neuronal retinal layers (3-5 μm per week), and reduction of a- and b-wave in ERG. EVC method can also induce glial cell activation and alterations of inflammation proteins, such as TNF-α and α2m.

CONCLUSIONEVC method can establish a robust, reliable, economic and highly reproducible glaucomatous animal model.

Animals ; Disease Models, Animal ; Electroretinography ; Female ; Glaucoma ; metabolism ; pathology ; Rats ; Rats, Wistar ; Retina ; metabolism ; pathology ; Retinal Neurons ; metabolism

Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma. Here, we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension (COH). In COH retinas, the microglial proliferation that occurred was inhibited by the P2X7 receptor (P2X7R) blocker BBG or P2X7R knockout, but not by the P2X4R blocker 5-BDBD. Treatment of primary cultured microglia with BzATP, a P2X7R agonist, mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway. Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration, which was completely blocked by 5-BDBD. In vivo and in vitro experiments demonstrated that ATP, released from activated Müller cells through connexin43 hemichannels, acted on P2X7R to induce microglial proliferation, and acted on P2X4R/P2X7R (mainly P2X4R) to induce microglial migration. Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
Adenosine Triphosphate/pharmacology* ; Animals ; Cell Proliferation ; Glaucoma/metabolism* ; Mice ; Microglia/metabolism* ; Receptors, Purinergic P2X4/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Retinal Ganglion Cells/metabolism*

PURPOSE: To investigate the differences in the histopathology and matrix metalloproteinase (MMP) expression in the Tenon's tissue of primary open-angle glaucoma (POAG) patients, primary angle-closure glaucoma (PACG) patients, and non-glaucomatous patients. METHODS: POAG and PACG patients, who underwent a trabeculectomy and had no history of ocular disease except glaucoma, were enrolled. The number and instillation period of topical eye drops were reviewed. For the controls, which were patients without glaucoma or a history of ocular surgery, the Tenon's tissue was obtained in the course of retinal detachment surgery. For glaucoma patients, the Tenon's tissue was obtained during the trabeculectomy. H&E and Masson's trichrome staining and immunohistochemistry for MMP-1, MMP-2, and MMP-9 were performed. A total of six eyes of POAG, six eyes of PACG, and four control eyes were evaluated. RESULTS: The duration of topical anti-glaucoma medication and the mean number of anti-glaucoma medications were similar in the POAG and PACG groups. The levels of MMP-1 and 2 were elevated in the POAG and PACG groups compared to the control group (p=0.03, 0.01, respectively). Compared with the control group, the MMP-2 level was higher in the POAG patients (p=0.01), whereas the MMP-1 was higher in the PACG patients (p=0.04). The levels of MMP-9 in the POAG and PACG patients were not significantly different from that of the control patients (p=0.48, 0.26). The levels of MMP-2 were significantly lower in the PACG patients than in the POAG patients (p=0.02). CONCLUSIONS: The MMP expression was altered in the Tenon's tissue of glaucoma patients compared to the control group. The levels of MMP-2 were lower in the PACG patients than in the POAG patients. These results suggest that there may be histopathological differences in the Tenon's tissue of POAG and PACG patients.
Adult ; Aged ; Connective Tissue/*enzymology ; Glaucoma, Angle-Closure/*enzymology/surgery ; Glaucoma, Open-Angle/*enzymology/surgery ; Humans ; Immunoenzyme Techniques ; Matrix Metalloproteinase 1/*metabolism ; Matrix Metalloproteinase 2/*metabolism ; Matrix Metalloproteinase 9/*metabolism ; Middle Aged ; Trabeculectomy

PURPOSE: To investigate the differences in the histopathology and matrix metalloproteinase (MMP) expression in the Tenon's tissue of primary open-angle glaucoma (POAG) patients, primary angle-closure glaucoma (PACG) patients, and non-glaucomatous patients. METHODS: POAG and PACG patients, who underwent a trabeculectomy and had no history of ocular disease except glaucoma, were enrolled. The number and instillation period of topical eye drops were reviewed. For the controls, which were patients without glaucoma or a history of ocular surgery, the Tenon's tissue was obtained in the course of retinal detachment surgery. For glaucoma patients, the Tenon's tissue was obtained during the trabeculectomy. H&E and Masson's trichrome staining and immunohistochemistry for MMP-1, MMP-2, and MMP-9 were performed. A total of six eyes of POAG, six eyes of PACG, and four control eyes were evaluated. RESULTS: The duration of topical anti-glaucoma medication and the mean number of anti-glaucoma medications were similar in the POAG and PACG groups. The levels of MMP-1 and 2 were elevated in the POAG and PACG groups compared to the control group (p=0.03, 0.01, respectively). Compared with the control group, the MMP-2 level was higher in the POAG patients (p=0.01), whereas the MMP-1 was higher in the PACG patients (p=0.04). The levels of MMP-9 in the POAG and PACG patients were not significantly different from that of the control patients (p=0.48, 0.26). The levels of MMP-2 were significantly lower in the PACG patients than in the POAG patients (p=0.02). CONCLUSIONS: The MMP expression was altered in the Tenon's tissue of glaucoma patients compared to the control group. The levels of MMP-2 were lower in the PACG patients than in the POAG patients. These results suggest that there may be histopathological differences in the Tenon's tissue of POAG and PACG patients.
Adult ; Aged ; Connective Tissue/*enzymology ; Glaucoma, Angle-Closure/*enzymology/surgery ; Glaucoma, Open-Angle/*enzymology/surgery ; Humans ; Immunoenzyme Techniques ; Matrix Metalloproteinase 1/*metabolism ; Matrix Metalloproteinase 2/*metabolism ; Matrix Metalloproteinase 9/*metabolism ; Middle Aged ; Trabeculectomy

BACKGROUNDHigh intraocular pressure (IOP) and low central corneal thickness (CCT) are important validated risk factors for glaucoma, and some studies also have suggested that eyes with more deformable corneas may be in higher risk of the development and worsening of glaucoma. In the present study, we aimed to evaluate the association between corneal biomechanical parameters and asymmetric visual field (VF) damage using a Corvis-ST device in patients with untreated normal tension glaucoma (NTG).

METHODSIn this observational, cross-sectional study, 44 newly diagnosed NTG patients were enrolled. Of these, 31 had asymmetric VF damage, which was defined as a 5-point difference between the eyes according to the Advanced Glaucoma Intervention Study scoring system. Corneal biomechanical parameters were obtained using a Corvis-ST device, such as time from start until the first and second applanation is reached (time A1 and time A2, respectively), cord length of the first and second applanation (length A1 and length A2, respectively), corneal speed during the first and second applanation (velocity A1 and velocity A2, respectively), time from start until highest concavity is reached (time HC), maximum amplitude at the apex of highest concavity (def ampl HC), distance between the two peaks at highest concavity (peak dist HC), and central concave curvature at its highest concavity (radius HC).

RESULTSTime A1 (7.19 ± 0.28 vs. 7.37 ± 0.41 ms, P = 0.010), length A1 (1.73 [1.70-1.76] vs. 1.78 [1.76-1.79] mm, P = 0.007), length A2 (1.58 [1.46-1.70] vs. 1.84 [1.76-1.92] mm, P< 0.001), peak dist HC (3.53 [3.08-4.00] vs. 4.33 [3.92-4.74] mm, P = 0.010), and radius HC (6.20 ± 0.69 vs. 6.59 ± 1.18 mm, P = 0.032) were significantly lower in the worse eyes than in the better eyes, whereas velocity A1 and def ampl HC were significantly higher (0.156 [0.149-0.163] vs. 0.145 [0.138-0.152] m/s, P = 0.002 and 1.19 ± 0.13 vs. 1.15 ± 0.13 mm, P = 0.005, respectively). There was no significant difference in time A2, velocity A2, and time HC between the two groups. In addition, no difference was observed in IOP, CCT, and axial length. In the univariate and multivariate analyses, some of the Corvis-ST parameters, including time A1 and def ampl HC, were correlated with known risk factors for glaucoma, and there was also a significant positive correlation between def ampl HC and age.

CONCLUSIONSThere were differences in dynamic corneal response parameters but not IOP or CCT between the paired eyes of NTG patients with asymmetric VF damage. We suggest that the shape of the cornea is more easily altered in the worse eyes of asymmetric NTG patients.

Aged ; Biomechanical Phenomena ; physiology ; Cornea ; metabolism ; physiology ; Cross-Sectional Studies ; Female ; Glaucoma ; metabolism ; physiopathology ; Humans ; Intraocular Pressure ; physiology ; Low Tension Glaucoma ; metabolism ; physiopathology ; Male ; Middle Aged ; Multivariate Analysis ; Prospective Studies ; Visual Fields ; physiology

To elucidate the mechanism of increased intraocular pressure in primary open-angle glaucoma (POAG), the protein profiles of aqueous humor obtained from POAG patients were compared with those of cataract patients as a control group. Aqueous humor proteins were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and detected by the ultrasensitive silver staining technique. In 79% of the samples taken from POAG patients, protein bands of 140,000 or 160,000 daltons were stained, but none were stained from cataract patients. The presence of these protein bands revealed statistically significant differences between the two groups. Protein bands of 140,000 or 160,000 daltons were evenly visible at all ages in POAG patients, and the positivity of bands had no correlation with sex or initial intraocular pressure level. It is possible that the ultrastructural changes of the aqueous outflow pathway in POAG may be related to the changes in the aqueous protein, presence of 140,000 or 160,000 daltons protein bands.
Adult ; Aged ; Aqueous Humor/*metabolism ; Cataract/metabolism ; Electrophoresis, Polyacrylamide Gel ; Eye Proteins/*metabolism ; Female ; Glaucoma, Open-Angle/*metabolism ; Humans ; Male ; Middle Aged ; Molecular Weight

We report on a case of cholesterosis bulbi concurrent with secondary glaucoma. A 36-year-old man, with a history of long-standing retinal detachment in his right eye after the irrigation and aspiration of a congenital cataract, presented with a clinical picture of elevated intraocular pressure and ocular pain. Upon slit-lamp examination, we found a ciliary injection and a pseudohypopyon of polychromatic crystals. Gonioscopic examination revealed a large amount of crystals deposited on the trabecular meshwork and mild rubeosis iridis, but the neovascularization of the angle could not be clearly confirmed due to the presence of so many crystals. Pars plana vitrectomy was performed to remove clusters of crystals and bevacizumab was injected intravitreally to treat iris neovascularization. Aqueous aspirate was examined by light microscopy and the typical highly refringent cholesterol crystals were identified. Intraocular pressure returned to a normal level after the bevacizumab injection, although severe cholesterosis was still evident in the anterior chamber. To our knowledge, this would be the first Korean case of cholesterosis bulbi combined with chronic retinal detachment and presumed neovascular glaucoma, which was treated by pars plana vitrectomy and intravitreal bevacizumab injection.
Adult ; Angiogenesis Inhibitors/therapeutic use ; Anterior Chamber/*metabolism ; Antibodies, Monoclonal, Humanized/*therapeutic use ; *Cholesterol ; Eye Diseases/complications/metabolism ; Follow-Up Studies ; Glaucoma/surgery ; Glaucoma, Neovascular/drug therapy/*etiology/surgery ; Humans ; Intraocular Pressure ; Male ; Vitrectomy/*methods

PURPOSE: Oxidative stress plays a critical role in the pathogenesis of glaucoma. Glutathione is a major antioxidant molecule present in intracellular or extracellular space. Herein, we aimed to examine circulating glutathione level in normal tension glaucoma (NTG), which comprises the largest proportion of glaucoma disease in the Korean population. METHODS: Nineteen NTG patients (NTG group) and 30 age- and gender-matched normal control subjects (control group) were included. Antecubital venous puncture was performed between 8 and 10 o'clock in the morning to obtain a 4 mL venous blood sample. Total glutathione level was measured by the spectrophotometric method at 412 nm. Correlation of total glutathione level with mean deviation and pattern standard deviation from the Humphrey visual field test was analyzed in the NTG group. RESULTS: Total glutathione level in circulating blood was 524.02 +/- 231.09 nmol and 586.06 +/- 156.08 nmol in the NTG group and the control group, respectively. The difference between these values was not statistically significant (p = 0.121, F = 2.212). Age had no significant effect on circulating total glutathione level in either the NTG group (p = 0.171, r = -0.328) or the control group (p = 0.380, r = -0.166). In the NTG group, circulating total glutathione level had no significant relationship with mean deviation (p = 0.226, F = 1.636) and pattern standard deviation (p = 0.200, F = 1.766) after correcting for age and gender. CONCLUSIONS: In NTG patients, circulating total glutathione levels were not different compared to those of normal subjects.
Disease Progression ; Eye/*metabolism ; Female ; Glutathione/*metabolism ; Humans ; Intraocular Pressure ; Low Tension Glaucoma/*metabolism/*pathology ; Male ; Middle Aged ; Oxidative Stress/*physiology ; Tonometry, Ocular