Influence of a Prostaglandin F2α Analogue on Corneal Hysteresis and Expression of Extracellular Matrix Metalloproteinases 3 and 9.

Purpose: Low corneal hysteresis (CH) is associated with an increased risk of glaucoma. Prostaglandin analogue (PGA) eye drops may exert their intraocular pressure (IOP)-lowering effect partially by increasing CH. Methods: Twelve pairs of organ-cultured human donor corneas were used in an ex vivo model. In each case, one cornea was treated with PGA (Travoprost) for 30 days, whereas the other served as an untreated control. IOP levels were simulated in an artificial anterior chamber model. CH was measured using the Ocular Response Analyzer (ORA). Corneal expression of matrix-metalloproteinases (MMPs) was assessed by immunhistochemistry and real-time polymerase chain reaction (RT-PCR). Results: Increased CH was observed in the PGA-treated corneas. However, at IOP between 10 and 20 mm Hg, CH was increased in PGA-treated corneas (13.12 ± 0.63 mm Hg; control: 12.34 ± 0.49 mm Hg), although not significantly (P = 0.14). CH was significantly increased at higher IOP levels (21-40 mm Hg; PGA-treated: 17.62 ± 0.40 mm Hg; control: 11.60 ± 0.39, P < 0.0001). Treatment with PGA resulted in increased expression of MMP-3 and MMP-9. Conclusions: CH was increased after exposure to PGA. However, this increase was significant only in eyes with higher IOP (>21 mm Hg). A significant increase in MMP-3 and -9 was observed in PGA-treated corneas, indicating structural changes in corneal biomechanics caused by PGA. Translational Relevance: PGAs alter biomechanical structures by directly upregulating MMP-3 and -9, and the increase in CH is dependent on the level of IOP. Therefore, PGAs may have a greater effect when baseline IOP is higher.

Idebenone prevents human optic nerve head astrocytes from oxidative stress, apoptosis, and senescence by stabilizing BAX/Bcl-2 ratio.

PURPOSE: Oxidative stress plays an important role in the pathogenesis of several neurodegenerative diseases including glaucoma. Astrocytes are supposed to play a role in glaucoma pathogenesis. This study investigates the antiapoptotic and cytoprotective effects of idebenone on optic nerve head astrocytes (ONHA) under oxidative stress. METHODS: ONHA were treated with 1 to 150 µM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species, senescence-associated ß-galactosidase activity were investigated. In addition, apoptosis (detection of histone-associated DNA fragmentation), and expression of BAX and Bcl-2, and their mRNA were determined after 48 hours and after hydrogen peroxide (H2O2) treatment. RESULTS: Idebenone concentrations from 1 to 50 µM showed no effects on ONHA viability. Pretreatment with 10 µM idebenone led to an increase in viability of ONHA after H2O2 treatment. In addition, idebenone pretreatment significantly attenuated the increase of histone-associated DNA fragmentation, induction of senescence-associated ß-galactosidase, and intracellular reactive oxygen species after treatment with H2O2. When ONHA cells were treated with idebenone and H2O2, real-time polymerase chain reaction and Western blot analysis yielded an increased expression of Bcl-2 and a decrease of BAX compared with those cells that were treated with H2O2 only. CONCLUSIONS: Idebenone reduced senescence, oxidative stress, and apoptotic cell death in cultured ONHA in vitro. Our results suggest that idebenone may help to protect ONHA in vivo, and therefore might be helpful in preventing the progression of glaucomatous degeneration.

Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma.

PURPOSE: To investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects. METHODS: A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT. RESULTS: Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014). CONCLUSION: Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary.