Acute Intraocular Hypertension Research Articles

Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells

Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-β-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma.

Melatonin Alleviates Pyroptosis of Retinal Neurons Following Acute Intraocular Hypertension

Melatonin Alleviates Pyroptosis of Retinal Neurons Following Acute Intraocular Hypertension

English

This study was conducted to demonstrate whether puerarin regulates glutamine synthetase (GS) activity following intraocular hypertension and has therapeutic potential in ophthalmology for the protection of optic nerves in patients with glaucoma. This study used a Wistar rat model of acute closed-angle glaucoma to investigate the effect of puerarin on GS activity in rat retina following intraocular hypertension. Acute intraocular hypertension was induced by increasing anterior chamber pressure to 110 mmHg for 30 min in the left eyes of 50 Wistar rats, while 5 additional Wistar rats lacking intraocular hypertension were used as a control group. Retinal GS activity was measured at 4, 12, 24, 36 and 72 h after induction of acute intraocular hypertension with/without puerarin treatment. Compared to the control group that lacked intraocular hypertension, GS activity in the intraocular hypertension group significantly decreased at 4 and 12 h (P<0.01), before increasing at 24 to 36 h and restoring to a level similar to the control group at 72 h. However, puerarin significantly (P<0.05) prevented the loss of GS activity seen in the intraocular hypertension group at 4 and 12 h, with no significant (P<0.05) difference in GS activity noted between the control group and rats treated with puerarin at these early time points. GS activity significantly (P<0.05) increased above control values at 24 and 36 h in the puerarin-treated group before eventually restoring to control levels at 72 h. These findings suggest puerarin protects GS activity in the early stages of retinal acute intraocular hypertension and may be of potential therapeutic benefit in acute closed-angle glaucoma. Key words: Puerarin, acute intraocular hypertension, glutathione synthetase.

Melatonin Alleviates Pyroptosis of Retinal Neurons Following Acute Intraocular Hypertension

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In vivo experimental study of acute intraocular hypertension in rabbit based on particle image velocimetry technique

At present, there are few in vivo experimental studies on anterior chamber flow field, and the relevant technologies are not mature. This study explores the experimental method and key techniques of particle image velocimetry (PIV) for the in vivo measurement of anterior chamber flow field with slow flow velocity in the rabbit with acute intraocular hypertension. The experimental process can be divided into three parts: model construction of rabbit eye with acute intraocular hypertension, in vivo eyeball preparation, and PIV setup. The following key techniques were mainly investigated: the optimal injection strategy of fluorescent particles and the correction strategy for image acquisition errors caused by the effects of image refraction and respiration. The results showed that the best injection method was that 15 μL of fluorescent particles solution was slowly injected into the anterior chamber through the lower part of iris and then the rabbit was released and waited for 13 h. In this way particles were completely distributed in the anterior chamber with the help of the aqueous humor circulation, and then in vivo PIV experiment could be performed. The eyeball should be covered with a square flume filled with ultrasonic coupling gel for the sake of imaging during the experiment. The Maximal Information Coefficient algorithm could be applied to correct the measured results before post-processing calculation. The results indicated that feasible injection strategy of fluorescent particles and the correction strategy for image acquisition are critical to obtain nice experiment effects for the in vivo PIV measurement of anterior chamber flow field in the rabbit with acute intraocular hypertension.

Melatonin Alleviates Pyroptosis of Retinal Neurons Following Acute Intraocular Hypertension.

Glaucoma is a multifactorial optic neuropathy progressively characterized by structural loss of Retinal Ganglion Cells (RGCs) and irreversible loss of vision. High Intraocular Pressure (HIOP) is a high-risk factor for glaucoma. It has been reported that the mechanisms of the loss of RGCs are explored in-depth after acute HIOP injury, such as apoptosis, autophagy, and necrosis. However, pyroptosis, a novel type of pro-inflammatory cell programmed necrosis, is rarely reported after HIOP injury. Research studies also showed that melatonin (MT) possesses substantial anti-inflammatory properties. However, whether melatonin could alleviate retinal neuronal death, especially pyroptosis, by HIOP injury is still unclear. This study explored pyroptosis of retinal neurons and the effects of melatonin in preventing retinal neurons from pyroptosis after acute HIOP injury. An acute HIOP model of rats was established by increasing the IOP followed by reperfusion. Western Blot (WB) was adopted to detect molecules related to pyroptosis at the protein level, such as GSDMD, GASMDp32, Caspase-1, and caspase-1 p20, and the products of inflammatory reactions, such as IL -18 and IL-1β. At the same time, immunofluorescence (IF) was used to co-localize caspase-1 with retinal neurons to determine the position of caspase-1 expression. Morphologically, ethidium homodimer III staining, a method commonly used to evaluate cell death, was carried out to stain dead cells. Subsequently, Lactate Dehydrogenase (LDH) cytotoxicity assay kit was used to quantitatively analyze the LDH released after cell disruption. The results suggested that pyroptosis played a vital role in retinal neuronal death, especially in the Ganglion Cell Layer, by acute HIOP injury and peaked at 6h after HIOP injury. Furthermore, it was found that melatonin (MT) might prevent retinal neurons of pyroptosis via NF-κ B/NLRP3 axis after HIOP injury in rats. Melatonin treatment might be considered a new strategy for protecting retinal neurons against pyroptosis following acute HIOP injury.

Marine-Steroid Derivative 5α-Androst-3β, 5α, 6β-triol Protects Retinal Ganglion Cells from Ischemia⁻Reperfusion Injury by Activating Nrf2 Pathway.

High intraocular pressure (IOP)-induced retinal ischemia leads to acute glaucoma, which is one of the leading causes of irreversible visual-field loss, characterized by loss of retinal ganglion cells (RGCs) and axonal injury in optic nerves (ONs). Oxidative stress and the inflammatory response play an important role in the ischemic injury of retinal and optic nerves. We focus on 5α-androst-3β, 5α, 6β-triol (TRIOL), a synthetic neuroactive derivative of natural marine steroids 24-methylene-cholest-3β, 5α, 6β, 19-tetrol and cholestane-3β, 5α, 6β-triol, which are two neuroactive polyhydroxysterols isolated from the soft coral Nephthea brassica and the gorgonian Menella kanisa, respectively. We previously demonstrated that TRIOL was a neuroprotective steroid with anti-inflammatory and antioxidative activities. However, the potential role of TRIOL on acute glaucoma and its underlying mechanisms remains unclear. Here, we report TRIOL as a promising neuroprotectant that can protect RGCs and their axons/dendrites from ischemic–reperfusion (I/R) injury in an acute intraocular hypertension (AIH) model. Intravitreal injection of TRIOL significantly alleviated the loss of RGCs and the damage of axons and dendrites in rats and mice with acute glaucoma. As NF-E2-related factor 2 (Nrf2) is one of the most critical regulators in oxidative and inflammatory injury, we further evaluated the effect of TRIOL on Nrf2 knockout mice, and the neuroprotective role of TRIOL on retinal ischemia was not observed in Nrf2 knockout mice, indicating that activation of Nrf2 is responsible for the neuroprotection of TRIOL. Further experiments demonstrated that TRIOL can activate and upregulate Nrf2, along with its downstream hemeoxygenase-1 (HO-1), by negative regulation of Kelch-like ECH (Enoyl-CoA Hydratase) associated Protein-1 (Keap1). In conclusion, our study shed new light on the neuroprotective therapy of retinal ischemia and proposed a promising marine drug candidate, TRIOL, for the therapeutics of acute glaucoma.

A Novel Synthetic Steroid of 2β,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia.

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that β,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs’ reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury.

Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins.

PurposeThis study was designed to develop and characterize a laser-induced model of acute intraocular hypertension that permits the study of the anterior segment of the eye.MethodsCD1 mice aged 5 and 8 weeks were examined for elevation of IOP induced by laser photocoagulation. We compared between occlusion of episcleral veins alone and when combined with 270° limbal vessel occlusion. Anterior chamber angle, corneal thickness, and retinal nerve fiber layer (RNFL) thickness were evaluated by anterior- and posterior-segment optical coherence tomography (OCT). Additionally, at day 7 post-procedure, the anterior segment was evaluated for inflammatory cellular presentation by histologic analysis and OCT, and limbal vessels and whole-mount retina were immunostained for CD31 and Brn3a, respectively. Brn3a-positive retinal ganglion cells (RGCs) were quantified with ImageJ software.ResultsAfter single or combined laser treatment in mice aged 5 or 8 weeks, IOP was significantly elevated for 5 to 6 days before returning to the baseline by day 7 post-procedure. Anterior segment assessment indicated less synechiae in the anterior chamber angle and better preserved limbal vessels with single versus combined laser treatment. Corneal thickness was significantly increased after single or combined treatment. No inflammatory cells were detected in the anterior chamber. The thickness of the RNFL and the density of RGCs were both significantly reduced after single or combined treatment.ConclusionsLaser photocoagulation of episcleral veins alone in CD1 mice aged 5 to 8 weeks may be used to induce ocular hypertension resulting in RNFL thinning and ganglion cell loss. This model permits the study of the anterior as well as the posterior segment of the eye.

Protective effect of curcumin for retinal ganglion cells in adult rabbits with acute intraocular hypertension

Protective effect of curcumin for retinal ganglion cells in adult rabbits with acute intraocular hypertension

Acute intraocular pressure after intravitreal injections, what is the mecanism?

AbstractPurpose To evaluate the mechanism of acute intraocular hypertension after intravitreal injections (IVI) of anti‐VEGF therapies.Methods A prospective study was performed to evaluate the IOP increase immediately after IVI of 0,05ml ranibizumab in 50 patients. We have also studied the correlation between IOP immediately after IVI and axial length, then with lens status. Moreover we have analysed the anterior chamber anatomic changes (anterior chamber volume and irido corneal angle), measures were taken before and 5mn after IVI by scheimpflug camera from Oculyzer® (Alcon).Results The IOP peak immediately after IVI was higher than 45 mmHg in 67,3% of patients. It was transient, decreasing after 15mn and returning to baseline in all patient after 45 mn. We found no statistically significant difference between pseudophakic eyes (n=30) and phakic eyes (n=20, p=0.80). No correlation was found between the axial length and the IOP spike (r=0.042, p=0,85). The mean change for the anterior chamber volume (ACV) is mild (0,33 mm3).The ACV increased in pseudophakic eyes (+15,64 mm3, +7,7%), but decreased in the phakic eyes (‐7,24 mm3, ‐4,4%). The mean change for irido corneal angle (ICA) is not significant (‐1,61°), it decreases in phakic eyes (‐2,97°, ‐7,2%) versus a quite neutral effect in pseudophakic eyes (+0,78°, + 1,5%).Conclusion The IOP spike is not correlated either with axial lengh or with lens status. ACV and ICA variations are different according to the lens status but remains mild. These results enhance the importance of the scleral biomechanical properties, and highlight an unpredictable peak. This could be an argument to propose a systematic prophylactic hypotensive treatment before IVI.

Detection of early neuron degeneration and accompanying glial responses in the visual pathway in a rat model of acute intraocular hypertension

Transsynaptic degeneration has been implicated in patients with primary open angle glaucoma (POAG) and animal models of chronic intraocular hypertension. Whether the sustained intraocular pressure (IOP) elevation is necessary for the induction of transsynaptic changes in the brain remains unclear. The aim of this study is to characterize the effects of acute and transient intraocular hypertension on the visual pathway of rats. Acute intraocular hypertension was induced in the right eye by anterior chamber perfusion. At 1 day, 3 days, 1 week, 2 weeks and 4 weeks after the operation, neuronal degeneration and glial responses in the retina, dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) were assessed using Nissl staining and immunohistochemistry. TUNEL staining was also performed to detect the neuronal apoptosis in the brain. At the first day after the operation, no obvious neuronal changes were detected in the retina or the brain. At 3 days, 46% of the retinal ganglion cells (RGCs) were lost. Atrophy of the contralateral optic tract was also observed. Meanwhile, the cross-sectional area of neurons in the contralateral dLGN and SC was decreased, while cell density in the same regions was increased. Glial activation in the retina occurred much earlier than the RGC loss. Co-expression of glial fibrillary acid protein (GFAP) and glutamine synthetase (GS) was observed in the end-feet and processes of Müller cells at 1 day after the operation. GFAP immunoreactivity was remarkably increased in the contralateral dLGN and SC at 3 days. It also showed a good co-localization with GS. All of aforementioned changes gradually progressed and persisted for the whole observation period. No TUNEL-positive cells were detected in the dLGN and SC at any post-operative time point. Taken together, these results illustrate that acute and transient intraocular hypertension is able to induce early onset and long-lasting neurodegenerative changes and the accompanying glial activation in the visual pathway. Brain changes may occur in parallel with the RGC loss. Reactive glial cells in the brain may participate in the clearance of aberrantly released glutamate and may serve as a sensitive marker of neuronal injury. Neuroprotection of the entire visual pathway and glia-target therapies may bring new insights into the glaucoma treatment.

Expression of glutamine synthetase mRNA in rat retina following acute intraocular hypertension

目的 观察急性高眼压后大鼠视网膜谷氨酰胺合成酶(GS)mRNA的表达变化.方法 前房灌注加压至110 mmHg,维持60 min.提取视网膜总RNA,以RT-PCR半定量GSmRNA.结果 大鼠前房加压解除后4 h,GSmRNA的表达较对照眼开始升高(P＜0.05),至24 h达高峰(P＜0.01),36 h降低(P＜0.05),72 h(P＞0.05)恢复至正常水平.结论 急性高眼压后大鼠视网膜GSmRNA的表达呈现明显升高过程,可能引起GS表达上调,促进谷氨酸转化为谷氨酰胺,从而减轻视网膜神经节细胞(RGCs)的损伤。

Hyperbaric oxygen treatment for experimental intraocular hypertension in rats: An lectroretinogram detection

Background Hyperbaric oxygen (HBO) is used for treating glaucoma, and affirmative curative effect has been obtained. HBO can sensitively reflect the obviously heightened b wave of electroretinogram (ERG) of injured tissue. Objective To observe the effect of HBO treatment on retinal function of rats with acute experimental intraocular hypertension with ERG. Design Randomized controlled experiment. Setting Department of Ophthalmology, Third Xiangya Hospital, Central South University; Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University; Department of Anatomy, Xiangya Hospital, Central South University. Materials Eighteen adult healthy Wistar rats, of either gender, weighing from 150 to 250 g, were provided by the Animal Room of Central South University. Type YLCO. 5/?A baby hyperbaric oxygen chamber, type LMS-2A two-channel physiological recorder, type BG-1 retina exposure system, Jiangwan type ?stereotaxis instrument. Methods This experiment was carried out in the Central South University between March and September 2006. Eighteen healthy Wistar rats were made into models of acute experimental intraocular hypertension. Then, they were divided into two groups: model group and HBO treatment group, with 9 in each group. Following 7 days of HBO treatment, the rats in HBO treatment group were placed in Type YLCO. 5/?A baby hyperbaric oxygen chamber, which was pressurized with pure oxygen (volume fraction 0.825±0.025). The treatment pressure was 0.2 MPa. The rats in HBO treatment group daily inhaled HBO for 80 minutes within 7 days; Rats in the model group were untouched. The performance of eyes was observed under the status of intraocular hypertension. ERG was recorded before, during and 7 days after modeling, meanwhile, the recovery rate of b wave from ERG was calculated. Recovery rate of b wave from ERG=(amplitude of b wave 7 days after modeling/amplitude of b wave before modeling)×100%. Main outcome measures ▪ Performance of eyes under the status of intraocular hypertension. ▪ Recovery rate of b wave of ERG. Results All the 18 rats were involved in the final analysis. ▪ Performance of eyes under the status of intraocular hypertension.: When intraocular pressure increased until b wave of ERG disappeared, two eyes of rats with corneal opacity, dilated pupils, pale iris and stiffened eyeballs were found. ▪ Recovery rate of b wave of ERG in the HBO treatment group was significantly higher than that in the model group [(60.04±19.33)% vs. (41.85±13.20)%, t =3.298, P < 0.01]. Conclusion HBO treatment can obviously promote the recovery of retinal function following acute intraocular hypertension.

Complications of posterior capsulotomy with the Nd:YAG laser. Study of 226 cases

Severe complications are classically described after capsulotomy: ocular hypertension, cystoid macular edema and secondary retinal detachment. A series of 226 patients having sustained Nd:YAG laser (PC). Posterior capsulotomy has been studied retrospectively in order to determine the rate of early complications (24 hours after PC) and late complications (up to 6 months after the PC). Fifteen patients (6.6%) presented acute temporary intraocular hypertension, 2 patients (0.9%) a retinal detachment, 2 patients (0.9%) a cystoid macular edema (CME). A total number of complications of 8.4% was observed, 1.8% were heavy. Transient rise of intraocular pressure is seen. Prophylactic treatment with acetazolamide 500 mg (Diamox) and timolol (Timoptic) is necessary.

Aqueous humor analysis after Nd:YAG laser capsulotomy with the laser flare-cell meter

Using the laser flare-cell meter (Kowa FC-1000), we conducted a prospective study analyzing the effect of Nd:YAG posterior capsulotomy on the quantity of aqueous particles, aqueous flare, and intraocular pressure in 65 eyes (58 patients). Aqueous particles increased at six hours, followed by flare rise which was significant at 18 hours after capsulotomy. Only 22 eyes (34%) had a significant flare rise over prelaser values. Anti-inflammatory therapy was necessary in only one patient. The mean intraocular pressure value did not rise significantly after capsulotomy. Acute intraocular hypertension (AIOHT) (> 7 mm Hg increase) occurred between three and six hours after laser therapy in 12 patients (19%), was related in time to particle rise, and always responded to a single dose of acetazolamide. Acute intraocular hypertension was strongly correlated with elevated aqueous particles (P < .0001) and somewhat correlated with flare rise (P <.036), but was not correlated with the intraocular lens position (bag or sulcus fixation). Our findings strongly suggest that trabecular meshwork clogging by debris generated by the cap-sulotomy is the mechanism at the origin of AIOHT.