Nuclear proteins and diabetic retinopathy: a review.

Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.

Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture.

BACKGROUND: Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. METHODS: Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. RESULTS: Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. CONCLUSION: Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.

RKI-1447, a Rho kinase inhibitor, causes ocular hypotension, actin stress fiber disruption, and increased phagocytosis.

PURPOSE: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. METHODS: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/ml for 48 h before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. RESULT: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 h. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 h (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. CONCLUSION: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.

Impact of pigment dispersion on trabecular meshwork cells.

PURPOSE: Dysfunction of the trabecular meshwork (TM) in pigmentary glaucoma contributes to increased aqueous humor outflow resistance and intraocular pressure. In this study, we investigated the effect of pigment dispersion on trabecular meshwork cells. METHODS: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then, analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose migrate, and contraction was quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. RESULTS: Stress fiber formation was increased in the pigment dispersion group (P) (60.1 ± 0.3%, n = 10) compared to control (C) (38.4 ± 2.5%, n = 11, p < 0.001). Phagocytosis declined (number of cells with microspheres in P = 37.0 ± 1.1% and in C = 68.7 ± 1.3%, n = 3, p < 0.001) and migration was reduced after 6 h (cells within the visual field over 6 h in P = 28.0.1 ± 2.3 (n = 12) and in C = 40.6 ± 3.3 (n = 13), p < 0.01). Pigment induced contraction at 24 h onwards (p < 0.01). Microarray analysis revealed that Rho signaling was central to these responses. CONCLUSION: Exposure of TM cells to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

Outflow enhancement by three different ab interno trabeculectomy procedures in a porcine anterior segment model.

PURPOSE: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. METHODS: In perfused porcine anterior segments, 90° of trabecular meshwork (TM) was ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 h, additional 90° of TM was removed. Intraocular pressure (IOP) and outflow facility were measured at 5 and 10 µl/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. RESULTS: At 5 µl/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90° of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µl/min compared with G and K (first ablation, 3.41 times increase versus 1.95 and 1.87; second ablation, 4.60 versus 2.50 and 1.74) with similar results at 10 µl/min (first ablation, 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation, 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. CONCLUSIONS: T, G, and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

Gene transfer to the outflow tract.

Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15-20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-ß and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

Stratification of phaco-trabectome surgery results using a glaucoma severity index in a retrospective analysis.

BACKGROUND: To stratify the outcomes of phacoemulsification combined with trabectome surgery using a new glaucoma severity index. METHODS: This is a retrospective, observational cohort study that included open angle glaucoma patients with visually significant cataract that had phacoemulsification combined with trabectome surgery. Exclusion criteria were follow-up less than 12 months, any other surgeries or diagnosis of neovascular or active uveitic glaucoma. Patients were stratified into four groups according to the Glaucoma Index (GI) that incorporated preoperative intraocular pressure (IOP), number of medications and visual field status. The primary outcome measures were IOP reduction and the success rate at 12 months. We examined the relationship between GI group and IOP and medications at one year with a linear regression analysis and survival with log-rank testing. RESULTS: Of 1374 patients, a total of 498 cases with 12 month follow-up were included in the study after applying the exclusion criteria. At one year, IOP of GI groups 1 through 4 was reduced by 2.9 ± 4.4, 3.6 ± 5.0, 3.9 ± 5.3, and 9.2 ± 7.6 mmHg for. Individuals in the next higher GI group had a 1.69 ± 0.2 mmHg larger IOP decrease. The success rate was 98%, 93%, 96% and 88% at one year for GI groups 1 to 4 (p < 0.05). CONCLUSIONS: A substantial IOP reduction was seen in subjects with more advanced glaucoma suggesting that the trabecular meshwork is the primary impediment to outflow and its ablation benefits those eyes relatively more than in mild glaucoma. A larger IOP reduction can be expected in individuals with a higher GI group that indicates a clinically more challenging glaucoma.

Steroid-induced glaucoma treated with trabecular ablation in a matched comparison with primary open-angle glaucoma.

BACKGROUND: To evaluate the outcomes of trabectome-mediated ab interno trabeculectomy in patients with steroid-induced glaucoma (SIG). DESIGN: A retrospective, observational cohort study performed in the Department of Ophthalmology, University of Pittsburgh Medical Center. PARTICIPANTS: The data of 60 patients with SIG and 484 controls with primary open-angle glaucoma (POAG) matched by age, gender and glaucoma index were collected from the Trabectome Study Group database. METHODS: Reduction of intraocular pressure (IOP) and medications were compared between POAG and SIG by multivariate regression. Kaplan-Meier was used for survival analysis. Success was defined as IOP ≤21 mmHg and at least 20% IOP reduction from baseline for any two consecutive visits after 3 months without secondary glaucoma surgery. Postoperative IOP and number of medications were compared with baseline in the SIG subgroups by the Wilcoxon test. MAIN OUTCOME MEASURES: Intraocular pressure reduction and 1-year success rate. RESULTS: Patients with SIG had a higher baseline IOP (31.4 ± 10.4 vs. 24.1 ± 7.6 mmHg, P < 0.01) and obtained a greater IOP reduction than controls with POAG (48.4% vs. 31.5%, P < 0.01). Multivariate regression showed that patients with SIG had an IOP reduction of 6.7 ± 1.1 mmHg more than those with POAG. Survival rates at 12 months were comparable at 86% in the SIG group and 85% in the POAG group (P = 0.47). Patients with SIG with a high baseline IOP, younger age and advanced glaucoma experienced a larger IOP drop. CONCLUSION: Trabectome appears to be an effective surgical treatment in reducing IOP for patients with SIG.

Effects of low-level laser irradiation on proliferation and functional protein expression in human RPE cells.

Low-level laser irradiation (LLLI) modulates a set of biological effects in many cell types such as fibroblasts, keratinocytes, and stem cells. However, no study to date has reported the effects of LLLI on retinal pigment epithelia (RPE) cells. The aim of this study was to investigate whether LLLI could enhance the proliferation of RPE cells and increase the expression of RPE functional genes/proteins. Human ARPE-19 cells were seeded overnight and treated with 8 J/cm(2) of LLLI. Cell proliferation was measured by CCK8 assay and cell cycle distribution was evaluated by FACS. The transcription of cell cycle-specific genes and RPE functional genes was quantified by RT-PCR. Moreover, the expression of ZO-1 and CRALBP were evaluated by immunostaining. A dose of 8 J/cm(2) of LLLI significantly increased proliferation and promoted cell cycle progression while upregulating the transcription of CDK4 and CCND1 and decreasing the transcription of CDKN2A, CDKN2C, and CDKN1B in human ARPE-19 cells. Additionally, LLLI enhanced the expression of ZO-1 and CRALBP in human ARPE-19 cells. In conclusion, LLLI could enhance the proliferative ability of human ARPE-19 cells by modulating cyclin D1, CDK4, and a group of cyclin-dependent kinase inhibitors. It also could increase the expression of RPE-specific proteins. Thus, LLLI may be a potential approach for the treatment of RPE degenerative diseases.

The Recent Advances in the Function and Mechanism of Caveolin-1 in Retinal Neovascularization.

Retinal neovascularization diseases have relatively high rates of evitable blindness. Abnormal retinal neovascularization is their main hallmark, which can damage the structure and function of the eye and lead to impaired vision. Caveolin-1 is a membrane protein that is expressed in many types of retinal cells and is involved in retinal neovascularization. This review presents a comprehensive analysis of global research on specific functions of caveolin-1 in retinal neovascularization. We believe that the mechanism of action of caveolin-1 might be related to the regulation of relevant signal pathways and looked ahead the application prospects of modulating caveolin- 1 in retinal neovascularization diseases.

Combination Therapy with Anti-VEGF and Intravitreal Dexamethasone Implant for Macular Edema Secondary to Retinal Vein Occlusion.

PURPOSE: To compare the safety and efficacy of intravitreal injection of ranibizumab alone or ranibizumab combined with dexamethasone intravitreal implant in the treatment of macular edema secondary to retinal vein occlusion. STUDY DESIGN: A single center, case-controlled, prospective cohort study (Clinical Trail Registration Number: ChiCTR2400080048). METHODS: A total of 44 patients were enrolled and randomized into the ranibizumab group (n = 23) and the combination group (ranibizumab combined with dexamethasone intravitreal implant) (n = 21). All patients received ranibizumab intravitreal injections in the first three months as the initial treatment. For the ranibizumab group, patients might receive repeat injections in case of the recurrence of macular edema; For the combination group, patients received an intravitreal injection of dexamethasone implant after the first injection of ranibizumab at the day 15. The main outcome was best-corrected visual acuity (BCVA) and reduction of central macular thickness. The secondary outcome were the numbers of recurrence, the average injection interval, and the numbers of injection. Adverse events were also recorded. RESULTS: The BCVAs in both groups were significantly improved compared with the baselines (all p < 0.001), but more increment in BCVA was noticed at the 3-month in the combination group (p = 0.022). Both groups showed a reduction of central macular thickness at all time points (p < 0.05). However, the combination group did not exhibit higher central macular thickness-reducing effects than the ranibizumab group (p > 0.05). Compared with the combination group, the ranibizumab group suffered a higher number of recurrences of macular edema (p < 0.001), a lower interval of injection (p = 0.050), and a higher number of injection (p < 0.011). The incidence of adverse events was not significant between the two groups (p = 0.944). CONCLUSIONS: Ranibizumab combined with dexamethasone injection sustainably improved the BCVA of retinal vein occlusion patients with a good safety profile.

Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma.

Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by progressive optic nerve degeneration and loss of visual field. Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway. Additionally, they also have neuroprotective and anti-scarring effects that can might increase the success rate of glaucoma filtration surgery. This review aims to summarize the current concept of Rho kinase inhibitors in the treatment of glaucoma from beach to bedside.

Assessment of macular and peripapillary choroidal thickness in non-arteritic anterior ischemic optic neuropathy: A meta-analysis.

BACKGROUND: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common optic neuropathy in adults aged ≥ 50 years. Transient non-perfusion or hypoperfusion of the optic nerve head circulation is believed to be the underlying cause of NAION. It has been suggested that peripapillary choroidal thickness (PCT) is altered after ischemic disorders of the optic nerve head, but the results have not always been consistent. To address this issue and provide evidence for the pathogenesis of NAION, we performed a meta-analysis to systematically evaluate macular choroidal thickness (MCT) and PCT in patients with NAION. METHODS: A comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases was performed until August 31, 2022. The main inclusion criterion was a case-control study in which MCT and PCT were measured using optical coherence tomography in patients with NAION. Mean difference (MD) and 95% confidence interval were calculated for continuous estimates. The Review Manager (V5.40) was used for the analysis. RESULTS: Nine studies comprising 663 eyes (283 NAION eyes and 380 healthy control eyes) were included (Newcastle-Ottawa Scale score ≥ 5). MCT and PCT were higher in eyes with chronic NAION (MD = 19.16, P = .04; MD = 35.36, P < .00001) and NAION fellow eyes (MD = 30.35, P = .0006; MD = 29.86, P = .04) than in healthy controls. No difference was noted in the MCT between eyes with acute NAION and healthy controls (MD = 2.99, P = .87). CONCLUSION: Increased MCT and PCT may be important anatomical and physiological features of the eyes in patients with NAION.

Rho-Kinase Inhibitors as Emerging Targets for Glaucoma Therapy.

Glaucoma, the leading cause of irreversible blindness worldwide, is a chronic and progressive optic neuropathy characterized by damage to the optic and retinal nerve fiber layers, which can lead to permanent loss of peripheral or central vision. Reduction of intraocular pressure (IOP) is the only known modifiable risk factor for preventing and treating glaucoma. Rho kinase (ROCK) inhibitors are a new class of glaucoma drugs with a novel mechanism of action and good safety profile. They exert neuroprotective effects, act on the trabecular tissue, increase the outflow of aqueous humor, and reduce intraocular pressure. However, they also cause local adverse reactions, including common conjunctival congestion and subconjunctival bleeding; however, most are self-limiting and temporary. Netarsudil (0.02%), a ROCK inhibitor, relaxes the trabecular meshwork, increases the outflow of aqueous humor, reduces scleral venous pressure, and directly decreases IOP. Conjunctival congestion can be reduced if netarsudil is administered at night. The combination of these medications is always more effective than the single drug. Ripasudil (0.4%), another ROCK inhibitor, also lowers IOP; however, conjunctival hyperemia is the most common adverse drug reaction. The purpose of this review is to summarize the effects and adverse reactions of ROCK inhibitors in the experimental trial stage and in clinical treatment in recent years, providing suggestions for future clinical drug use, and research and development to reduce the side effects of these drugs, maximize the potential for reducing IOP, and improve the therapeutic effect.

Bilateral malignant glaucoma with bullous keratopathy: A case report.

BACKGROUND: Malignant glaucoma, caused by aqueous misdirection, is a challenging post-surgical complication presented with normal/high intraocular pressure and shallowing of the central and peripheral anterior chambers. Its incidence is about 0.6%-4.0%. It can be secondary to filtering surgeries, laser iridotomy, and cataract surgery. Short axial length and a history of angle closure glaucoma are its main risk factors. Here, we report a bilateral malignant glaucoma with bullous keratopathy in the patient's left eye. CASE SUMMARY: We present a case of bilateral malignant glaucoma. The cause of malignant glaucoma for each eye of this patient was different. Hence, the management strategy and selection of surgical methods were also different. However, the normal anterior chamber was ultimately maintained, and maximum visual function was preserved. Even though the left eye received multiple surgeries and corneal endothelial decompensation occurred, the formation of a retroendothelial fibrous membrane partially compensated for the function of the corneal endothelium. CONCLUSION: The formation of a retroendothelial fibrous membrane partially compensated for the function of the corneal endothelium.

Role of Oxidative Stress in Retinal Disease and the Early Intervention Strategies: A Review.

The retina, owing to its cellular anatomy and physical location, is susceptible to generating reactive oxygen species (ROS), which are associated with several major retinal diseases. When ROS exceeds the body's natural antioxidants, the retina is in a state of oxidative stress, which is recognized as the pathogenesis of retinal diseases. The early stage of the pathogenic process is an adaptive change in which oxidative stress and endogenous defense mechanisms occur. If no treatment is applied, the retinal diseases will progress to the pathological stage with neuronal and vascular dysfunction or damage and even blindness. This review summarizes the role of oxidative stress in several common retinal diseases, including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. In addition, we discuss the early intervention strategies for these diseases. An outline is provided to identify potential intervention targets for further research. Early intervention for retinal diseases is necessary and urgent and may offer hope to improve patients' quality of life through functional vision.

Giant Intracranial Xanthoma with Cloudy Vision as the First Symptom: A Case Report and Literature Review.

A 31-year-old male with mild dizziness complained of cloudy vision in his right eye for 5 days. The visual acuity of both eyes was normal, while the visual contrast sensitivity of both eyes slightly reduced. Fundus examination showed the swollen and radial superficial hemorrhage of his both optic nerves. Brain MRI scan indicated a huge tumor in the right temporal lobe with clear boundary, close to the skull. The midline structure shifted to the left. Blood tests indicated no hyperlipidemia or lipid disorders. The patient then received tumor resection. The size of the tumor was 5.6 cm × 7.5 cm × 10.1 cm. Histology suggested many foam cell accumulations and the tumor was positive for CD34, CD99, Vimentin, ß-Catenin and CD68, but negative for EMA, GFAP, IDH-1, Oliga-2, PR, S-100, and CD1a. Three months after surgery, MRI showed the midline structure was back to normal. The swollen and radial superficial hemorrhage of optic nerves had disappeared. The visual acuity and visual field remained normal.

Ripasudil in a Model of Pigmentary Glaucoma.

Purpose: To investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma. Methods: In vitro trabecular meshwork (TM) cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115. Results: The percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8% ± 2.9%; PK115: 11.6% ± 3.3%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7% ± 2.1%, PK115: 33.4% ± 0.8%, P <0.01). Migration recuperated at 12 hours with K-115 treatment (P: 19.1 ± 4.6 cells/high-power field, PK115: 42.5 ± 1.6 cells/high-power field, P < 0.001). Ex vivo, eyes became hypertensive from pigment dispersion but were normotensive after treatment with K-115 (P: 20.3 ± 1.2 mm Hg, PK115: 8.9 ± 1.7 mm Hg; P < 0.005). Conclusions: In vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure. Translational Relevance: This ex vivo pigmentary glaucoma model provides a readily available basis to investigate new drugs such as the rho-kinase inhibitor studied here.

Intraocular pressure reduction in a pigmentary glaucoma model by Goniotome Ab interno trabeculectomy.

PURPOSE: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. METHODS: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. RESULTS: After the first 90° TM excision, IOP was significantly lower in G (10.2±2.4 mmHg, n = 7) than C (20.0±2.0mmHg, n = 8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n = 7) was significantly lower than C (20.3±1.7 mmHg, n = 8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n = 7) was higher than C (0.16±0.01 µl/min/mmHg, n = 8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P = 0.20) or outflow facility (P = 0.17) further. CONCLUSIONS: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility.

Gypenosides attenuate lipopolysaccharide-induced optic neuritis in rats.

PURPOSE: To evaluate the effect of gypenosides (GPs) on lipopolysaccharide (LPS)-induced optic neuritis rats. METHODS: Optic neuritis was induced by a single microinjection of LPS into the optic nerve of Sprague Dawley rats. GPs (400 mg/kg) was administrated by gavage for 21 days. The optic nerve structure changes and demyelination were observed after hematoxylin & eosin and Luxol-fast blue staining. Apoptosis of retinal ganglion cells (RGCs) was evaluated using Brn3a-TUNEL double staining. Expression of CD68 and glial fibrillary acidic protein (GFAP) were detected using immunofluorescence staining. The mRNA levels of inflammatory factors were measured using quantitative real-time PCR. The protein expression levels in the signal transducer and activator of transcription (STAT) and nuclear factor-κB (NF-κB) pathways were detected using Western blot. RESULTS: GPs treatment prevented the optic nerve structure changes and demyelination in the rats with optic neuritis. GPs treatment downregulated LPS-induced overexpressions of CD68, GFAP and pro-inflammatory factors. GPs treatment inhibited STAT1 and 3 phosphorylation and NF-κB nuclear translocation in the optic nerve and retina of rats with optic neuritis. CONCLUSION: GPs attenuate LPS-induced inflammation, demyelination and optic nerve damage which may be associated with the inhibition of the NF-κB and STAT pathways.