- Axogenic mechanism enhances retinal ganglion cell excitability during early progression in glaucoma. [Journal Article]
- PNProc Natl Acad Sci U S A 2018 Feb 20
- Diseases of the brain involve early axon dysfunction that often precedes outright degeneration. Pruning of dendrites and their synapses represents a potential driver of axonopathy by reducing activit...
Diseases of the brain involve early axon dysfunction that often precedes outright degeneration. Pruning of dendrites and their synapses represents a potential driver of axonopathy by reducing activity. Optic nerve degeneration in glaucoma, the world's leading cause of irreversible blindness, involves early stress to retinal ganglion cell (RGC) axons from sensitivity to intraocular pressure (IOP). This sensitivity also influences survival of RGC dendrites and excitatory synapses in the retina. Here we tested in individual RGCs identified by type the relationship between dendritic organization and axon signaling to light following modest, short-term elevations in pressure. We found dendritic pruning occurred early, by 2 wk of elevation, and independent of whether the RGC responded to light onset (ON cells) or offset (OFF cells). Pruning was similarly independent of ON and OFF in the DBA/2J mouse, a chronic glaucoma model. Paradoxically, all RGCs, even those with significant pruning, demonstrated a transient increase in axon firing in response to the preferred light stimulus that occurred on a backdrop of generally enhanced excitability. The increased response was not through conventional presynaptic signaling, but rather depended on voltage-sensitive sodium channels that increased transiently in the axon. Pruning, axon dysfunction, and deficits in visual acuity did not progress between 2 and 4 wk of elevation. These results suggest neurodegeneration in glaucoma involves an early axogenic response that counters IOP-related stress to excitatory dendritic architecture to slow progression and maintain signaling to the brain. Thus, short-term exposure to elevated IOP may precondition the neural system to further insult.
- Ocular complications after cosmetic periocular diode laser application to the eyelids. [Journal Article]
- JCJ Cosmet Laser Ther 2018 Feb 20; :1-2
- A 25-year-old woman underwent diode laser application on the both upper eyelids in the dermatology department of a private hospital to obtain a cosmetic healing of the reddish look on her eyelids wit...
A 25-year-old woman underwent diode laser application on the both upper eyelids in the dermatology department of a private hospital to obtain a cosmetic healing of the reddish look on her eyelids without any protective lenses. The patient experienced severe uveitis, atonic pupils, raised intraocular pressure, and increased sensitivity to light in her eyes on the following day of the procedure. Topical steroids and pressure-lowering agents were able to treat the acute uveitis and glaucoma, unfortunately the patient suffered from irreversible atonic and atrophic pupils and photosensitivity. It is recommended that cosmetic laser application on the periocular area should be avoided, and if it is still to be performed, it should be applied cautiously and the patient should be informed of the potential ocular complications.
- Impact of aromatase absence on murine intraocular pressure and retinal ganglion cells. [Journal Article]
- SRSci Rep 2018 Feb 19; 8(1):3280
- We hypothesize that aromatase, an enzyme that regulates estrogen production, plays a significant role in the control of intraocular pressure (IOP) and retinal ganglion cells (RGCs). To begin to test ...
We hypothesize that aromatase, an enzyme that regulates estrogen production, plays a significant role in the control of intraocular pressure (IOP) and retinal ganglion cells (RGCs). To begin to test our hypothesis, we examined the impact of aromatase absence, which completely eliminates estrogen synthesis, in male and female mice. Studies were performed with adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice. IOP was measured in a masked fashion in both eyes of conscious mice at 12 and 24 weeks of age. Retinas were obtained and processed for RGC counting with a confocal microscope. IOP levels in both 12- and 24-week old female ArKO mice were significantly higher than those of age- and sex-matched WT controls. The mean increase in IOP was 7.9% in the 12-week-, and 19.7% in the 24-week-old mice, respectively. These changes were accompanied by significant 9% and 7% decreases in RGC numbers in the ArKO female mice, relative to controls, at 12- and 24-weeks, respectively. In contrast, aromatase deficiency did not lead to an increased IOP in male mice. There was a significant reduction in RGC counts in the 12-, but not 24-, week-old male ArKO mice, as compared to their age- and sex-matched WT controls. Overall, our findings show that aromatase inhibition in females is associated with elevated IOP and reduced RGC counts.
- Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis. [Review]
- EEye (Lond) 2018 Feb 19
- Normal tension glaucoma (NTG) is an exception in the "glaucoma family" where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other ...
Normal tension glaucoma (NTG) is an exception in the "glaucoma family" where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other causes can then lead to glaucomatous optic disc change and visual field loss in NTG? Several possibilities will be discussed. Among them a higher sensitivity to normal pressure, vascular dysregulation, an abnormally high translaminar pressure gradient and a neurodegenerative process due to impaired cerebrospinal fluid dynamics in the optic nerve sheath compartment. There are many excellent review papers published on normal tension glaucoma (NTG). The aim of this paper is therefore not to add another extensive review on NTG but rather to focus on and to discuss some possible mechanisms that are thought to be involved in the pathophysiology of NTG and to discuss the stronger and weaker aspects of each concept. The fact that several concepts exist suggests that NTG is still not very well understood and that no single mechanism on its own might adequately explain NTG.
- Incidence of ocular hypertension after intravitreal injection of anti-VEGF agents in the treatment of neovascular AMD. [Journal Article]
- RJRom J Ophthalmol 2017 Jul-Sep; 61(3):207-211
- Purpose. The assessment of the incidence of ocular hypertension over a period of 1 year in patients treated with multiple intravitreal injections of anti-VEGF agents for neovascul...
Purpose. The assessment of the incidence of ocular hypertension over a period of 1 year in patients treated with multiple intravitreal injections of anti-VEGF agents for neovascular AMD.Methods.The study comprised 58 eyes diagnosed with neovascular age-related macular degeneration and receiving PRN intravitreal treatment with anti-VEGF agents (bevacizumab or aflibercept). The follow-up period was 1 year. Intraocular pressure was measured by using the Goldmann applanation tonometry before the intravitreal injection, at 24 hours after the administration of the anti-VEGF agent and at 1 and 4 weeks. Patients diagnosed with glaucoma or who underwent ophthalmic surgery were excluded.Results.The patients received an average of 7.54 intravitreal injections. The mean baseline intraocular pressure was 15.3 mm Hg; 19.8 mm Hg at 24 hours; 17,4 mmHg at 1 week and 14.8 mmHg at 4 weeks after the administration of the anti-VEGF agent. 4 patients required long-term topical hypotensive treatment. Raised intraocular pressure was related to increased frequency of treatment. At 1 year follow up, an average difference of 2.1 mmHg compared to baseline was registered in the cases that have received more than 6 intravitreal injections. By comparison, in the cases treated with a reduced number of doses of intravitreal anti VEGF agent, the difference from baseline was 0,9 mmHg. There were no significant differences in mean IOP depending on the anti VEGF (bevacizumab or aflibercept) agent used.Conclusions.Intravitreal treatment with anti VEGF agents produces a transient increase in intraocular pressure, predominantly immediately following administration, without causing long-term increased values.
- [Significance of Helicobacter pylori Diagnostic in Glaucoma]. [Journal Article]
- KMKlin Monbl Augenheilkd 2018; 235(2):135-139
- Glaucoma is one of the most common causes for blindness worldwide. Even if some risk factors for this disease are known, like increased intraocular pressure or increased age, its pathomechanism is st...
Glaucoma is one of the most common causes for blindness worldwide. Even if some risk factors for this disease are known, like increased intraocular pressure or increased age, its pathomechanism is still not fully understood. Multiple studies recently analyzed the role of a Helicobacter pylori infection in the glaucoma pathogenesis. Several studies showed a correlation, while others did not come to this conclusion. In summary, it is very likely that a Helicobacter pylori infection coincides with an increased risk for a primary open-angle or normal-tension glaucoma. Still, larger studies, with strict inclusion and exclusion criteria, as well as age-matched control groups, are needed to find out if a Helicobacter pylori infection really leads to a higher risk for glaucoma.
- Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma. [Review]
- JJJpn J Ophthalmol 2018 Feb 14
- Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling messenger and downstream effector of Rho, is activated by several bioactive factors in the aqueous humor (AH). Rho-ROCK signal...
Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling messenger and downstream effector of Rho, is activated by several bioactive factors in the aqueous humor (AH). Rho-ROCK signaling regulates a wide spectrum of fundamental cellular events, including cell adhesion, motility, proliferation, differentiation, and apoptosis. Previous studies, including our own, found that ROCK inhibitor lowers intraocular pressure (IOP) via a direct effect on the conventional AH outflow pathway, by regulation of contractile properties, fibrotic activity, and permeability of the trabecular meshwork (TM) and Schlemm's canal (SC) tissues, influencing extracellular matrix (ECM) production. Recently, a novel ROCK inhibitor, ripasudil, has been introduced in Japan. Other ROCK inhibitors are now in clinical trials as new IOP-lowering drugs for glaucoma patients. To date, ripasudil, administered together with other glaucoma medications, has proved safe and efficient in lowering IOP as well as additional effects such as prostaglandin analogs, beta-blockers, and carbonic anhydrase inhibitors, all of which help lower IOP by different mechanisms. In addition, we found that long-term treatment with ripasudil exerted an additional IOP-lowering effect, especially in eyes with high IOP, suggesting that late-onset remodeling of the ECM in glaucomatous eyes may elicit mild and delayed changes in IOP levels. ROCK inhibitors have also shown several additional effects, including increased retinal blood flow, direct protection of neurons against various types of stress, and regulation of wound healing; these benefits may potentially be useful in glaucoma treatment.
- PROGRESSION OF RETINAL ISCHEMIA IN A CASE OF MACULAR TELANGIECTASIA TYPE 1 AFTER RANIBIZUMAB INJECTION: OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS. [Journal Article]
- RCRetin Cases Brief Rep 2018 Feb 13
- CONCLUSIONS: Optical coherence tomography angiography may represent an indispensable diagnostic technique, complementary to traditional imaging, in the evaluation of the effects of anti-vascular endothelial growth factor therapy in patients with MacTel Type 1.
- Hsp70 protects human trabecular meshwork cells injury induced by UVB through Smad pathway. [Journal Article]
- PPharmazie 2017 Jun 01; 72(6):334-337
- CONCLUSIONS: Hsp70 might improve cell viability and inhibit TM apoptosis by inhibition of the Smad pathway. Hsp70 is a potential therapeutic target for the treatment of glaucoma.
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- Long-term titrated IOP control with one, two, or three trabecular micro-bypass stents in open-angle glaucoma subjects on topical hypotensive medication: 42-month outcomes. [Journal Article]
- COClin Ophthalmol 2018; 12:255-262
- CONCLUSIONS: The standalone implantation of either single or multiple iStent®device(s) produced safe, clinically meaningful IOP and medication reductions through 42 months postoperatively, with incrementally greater and more sustained reductions in multi-stent eyes.