The Effects of ROCK Inhibitor on Prevention of Dexamethasone-Induced Glaucoma Phenotype in Human Trabecular Meshwork Cells.

Purpose: This study investigated the effects of dexamethasone (Dex) on human trabecular meshwork (TM) cells, a model of glucocorticoid-induced glaucoma, and evaluated the impact of ripasudil (Rip) as a co-delivery or sequential dosing strategy. Methods: In vitro experiments were conducted to assess the effects of Dex and Rip on TM cells. Confocal microscopy was used to evaluate the impact of Dex and Rip on F-actin staining signals. Contractility of the TM cells upon Dex and Rip treatment mimicking co-delivery and sequential delivery was quantified using collagen gel contraction assay. Transepithelial electrical resistance (TEER) values and fluorescein isothiocyanate (FITC)-dextran permeability were also measured to assess the impact of Dex and Rip on TM cells. Results: Dex and Rip did not exhibit cytotoxicity at the maximum tested concentration (20 µM). Dex-treated TM cells exhibited higher F-actin staining signals compared to controls, which were reduced when co-treated with Rip. Rip inhibited Dex-induced collagen gel contraction activity in both co-delivery and sequential treatments. Dex resulted in increased TEER values as the dose increased, whereas TEER values were maintained when co-treated with Rip. Conclusions: Co-delivery of Rip has the potential to prevent glaucoma symptoms when patients are treated with Dex. This study highlights the importance of identifying strategies to reduce the side effects of prolonged use of glucocorticoids, such as Dex, in the treatment of various diseases. Translational Relevance: This study demonstrates the potential of co-delivering ripasudil with dexamethasone to mitigate glucocorticoid-induced ocular hypertension and a secondary glaucoma that resembles primary open-angle glaucoma, providing insights for the development of novel preventive strategies in clinical care.

The Mediterranean Diet and Age-Related Eye Diseases: A Systematic Review.

The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and dry eye syndrome (DES). In this study, we systematically reviewed studies in the literature that had reported associations between adherence to the MD and the five above-mentioned AREDs. Randomized controlled trials as well as prospective and retrospective observational studies were included; 1164 studies were identified, of which 1, 2, 9, 2 and 4 studies met our eligibility criteria for cataract, glaucoma, AMD, DR, and DES, respectively. According to these studies, higher MD adherence was associated with reduced risks of incident DR, incident AMD and progression to late AMD, but whether early and neovascular AMD could be alleviated remained to be debated. The results regarding the effects of the MD on DES were mixed, with three studies reporting an associations between MD and decreased severity or incidence of DES, whereas one study reported the opposite. No significant associations were observed between the MD and cataract or glaucoma. Generally, convincing evidence suggested a protective effect of the MD against AMD and DR. However, the evidence for cataract, glaucoma, and DES was less conclusive, and high-quality studies are needed for comprehensive evaluations of the potential benefits of MD on these eye diseases.

Associations Between Niacin Intake and Glaucoma in the National Health and Nutrition Examination Survey.

PRCIS: This study examined the association between dietary niacin intake and glaucoma in the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Increased niacin intake was associated with lower odds of glaucoma overall and among women. PURPOSE: To examine the association between dietary niacin intake and glaucoma in the 2005-2008 NHANES. MATERIALS AND METHODS: This cross-sectional study included adult participants of the 2005-2008 NHANES. The exposure was dietary niacin intake, which was examined as a continuous and categorical variable. The outcome was glaucoma as defined by regraded disc images. Covariates included age, sex, race/ethnicity, education level, income, body mass index, smoking status, alcohol use, cardiovascular disease, diabetes mellitus, daily energy intake, vitamin B2 and B6 consumption, and macular degeneration. Adjusting for all covariates, logistic regression was performed to examine the association between niacin intake and glaucoma in the overall population and stratified by sex. RESULTS: The weighted population included 5371 individuals (109,734,124 weighted), of whom 55 (1.0%) had glaucoma. Each 1 mg increase in niacin intake was associated with a 6% decreased odds of glaucoma odds [adjusted odds ratio (aOR) = 0.94, 95% CI = 0.90, 0.98]. Among women, increased niacin intake was associated with decreased odds of glaucoma both with niacin as a continuous (aOR = 0.89, 95% CI = 0.80, 0.99 per 1 mg increase in niacin intake) and binary variable (aOR = 0.35, 95% CI = 0.14, 0.90 for higher vs lower niacin intake). CONCLUSIONS: In the 2005-2008 NHANES population, higher levels of niacin intake were associated with decreased odds of glaucoma overall and in women. Further studies are needed to examine the potential protective effects of niacin on glaucoma risk.

From bench to behaviour: The role of lifestyle factors on intraocular pressure, neuroprotection, and disease progression in glaucoma.

Current glaucoma management centres on intraocular pressure (IOP) reduction through pharmacological and surgical therapy. Despite broad interest in active management of glaucoma through lifestyle modifications, such recommendations have yet to be incorporated into standards of treatment. In this review, noteworthy preclinical studies and their translations in clinical populations are discussed to evaluate the roles of lifestyle factors in lowering IOP, offering neuroprotection, and/or slowing disease progression in those with open-angle glaucoma. Current literature suggests that aerobic exercise may be associated with neuroprotection and decreased disease progression. Mindfulness is associated with IOP reductions and neuroprotection. Caffeine is associated with mild, transient IOP elevations of uncertain significance. Nicotinamide supplementation is associated with neuroprotection and short-term visual function improvement. This review also highlights knowledge gaps regarding these factors and opportunities to strengthen our understanding of their role in glaucoma, including future preclinical studies that elucidate underlying mechanisms and clinical studies with additional functional endpoints and longer follow-up.

AAV2-Mediated Expression of HspB1 in RGCs Prevents Somal Damage and Axonal Transport Deficits in a Mouse Model of Ocular Hypertension.

Purpose: Ocular hypertension is a significant risk factor for vision loss in glaucoma caused by the death of retinal ganglion cells (RGCs). We investigated whether small heat shock proteins (sHsps) expressed in RGCs protect those cells against ocular hypertension in mice. Methods: AAV2 vectors encoding genes for one of the following four human sHsps: HSPB1, HSPB4, HSPB5, or HSPB6 were constructed for RGC-specific expression. Ischemia/reperfusion was induced by elevating the intraocular pressure (IOP) to 120 mm Hg for one hour, followed by a rapid return to normal IOP. Microbeads (MB) were injected into the anterior chamber of mice to induce ocular hypertension. RGC death and glial activation were assessed by immunostaining for Brn3a, RBPMS, Iba1, and glial fibrillary acid protein in retinal flat mounts. RGC axonal defects were evaluated by anterograde transport of intravitreally injected cholera toxin-B. RGC function was assessed by pattern electroretinography. Results: Among the sHsps, HspB1 offered the best protection against RGC death from ischemia/reperfusion injury in the mouse retina. Intravitreal administration of AAV2-HSPB1 either two weeks before or one week after instituting ocular hypertension resulted in significant prevention of RGC loss. The MB-injected mice showed RGC axonal transportation defects, but AAV2-HSPB1 administration significantly inhibited this defect. AAV2-HSPB1 prevented glial activation caused by ocular hypertension. More importantly, a single injection of AAV2-HSPB1 protected RGCs long-term in MB-injected eyes. Conclusions: The administration of AAV2-HSPB1 inhibited RGC death and axonal transport defects and reduced glial activation in a mouse model of ocular hypertension. Translational Relevance: Our results suggested that the intravitreal delivery of AAV2-HSPB1 could be developed as a gene therapy to prevent vision loss on a long-term basis in glaucoma patients.

Repurposing Antihypertensive Drugs for the Prevention of Glaucoma: A Mendelian Randomization Study.

Purpose: Several antihypertensive drugs have been used for the treatment of glaucoma. However, the effect of hypertension and antihypertensive drugs on glaucoma is still unclear. Methods: Leveraging large-scale genome-wide association study summary statistics for glaucoma (Ncase = 4737, Ncontrol = 458,196), blood pressure (BP) (N = 422,771), and intraocular pressure (IOP) (N = 31,269), the genetic correlation and causal relationship of genetically assessed IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 12 types of antihypertensive drugs with glaucoma were evaluated using linkage disequilibrium score (LDSC) regression, univariate mendelian randomization (MR), and multivariable MR. Results: LDSC results showed a suggestive association of glaucoma with SBP (Rg = 0.12, P = 0.0076) and DBP (Rg = 0.17, P = 0.02). In univariate MR, genetically elevated BP in participants was not identified to lead to an increased glaucoma risk (SBP: odds ratio [OR], 1.05 [95% confidence interval {CI}, 0.91-1.21]; P = 0.52; DBP: OR, 1.07 [95% CI, 0.93-1.23]; P = 0.34). The results of univariate MR were replicated in multivariable MR (SBP: OR, 0.95 [95% CI, 0.71-1.29]; P = 0.75; DBP: OR, 1.13 [95% CI, 0.85-1.51]; P = 0.41). Furthermore, there was insufficient evidence to suggest that antihypertensive drugs were associated with glaucoma. Conclusions: Together, controlling BP may not help prevent and treat glaucoma, and antihypertensive drugs may neither treat nor worsen glaucoma. Translational Relevance: Treating with antihypertensive drugs should not be used as an intervention for patients with glaucoma.

Healthy Lifestyle Score and Incidence of Glaucoma: The Sun Project.

BACKGROUND: The relationship between modifiable risk factors, such as diet and lifestyle, and glaucoma remains controversial. We analyse the effect of the Mediterranean lifestyle (ML) on glaucoma incidence in the "Seguimiento Universidad de Navarra" (SUN) Project. METHODS: The SUN Healthy Lifestyle Score (SHLS) includes 10 healthy habits: never having smoked, moderate to high physical activity, Mediterranean diet adherence, moderate alcohol consumption, low television exposure, no binge drinking, short afternoon napping, meeting up with friends, working at least 40 h/wk, and low body mass index. The information was collected biennially through self-reported questionnaires. The relationship between new glaucoma cases and the SHLS was assessed by Cox regression using hazard ratios. Crude, multi-adjusted, and sensitivity analyses were performed. RESULTS: During a median of 12 years of follow-up, 261 (1.42%) new cases of glaucoma were identified among 18,420 participants. After adjusting for potential confounders, participants in the healthiest SHLS category showed a significantly reduced risk of glaucoma compared to those in the lowest SHLS category (adjusted HR = 0.51, 95% CI = 0.28-0.93). For each point added to the SHLS, the risk of glaucoma relatively dropped 5%. CONCLUSIONS: Higher adherence to a ML, measured by the SHLS, was significantly associated with a lower risk of developing glaucoma. Based on our study, the ML is a protective factor for glaucoma incidence.

Nutritional supplementation in the prevention and treatment of glaucoma.

Glaucoma is a chronic optic neuropathy that creates a significant burden on public health. Oxidative stress is hypothesized to play a role to glaucoma progression, and its reduction is being analyzed as a therapeutic target. Dietary antioxidants play a crucial role in helping provide insight into this hypothesis. We reviewed 71 trials, interventional, in-vivo and Iin vitro, including 11 randomized controlled trials, to determine if adjunctive nutritional supplementation could lead to a reduction in oxidative stress and prevent glaucomatous progression. Many laboratory findings show that vitamins and natural compounds contain an abundance of intrinsic antioxidative, neuroprotective and vasoprotective properties that show promise in the treatment and prevention of glaucoma. Although there is encouraging early evidence, most clinical findings are inconclusive. The group of B vitamins appear to have the greatest amount of evidence. Other compounds such as flavonoids, carotenoids, curcumin, saffron, CoQ10, gingko biloba, and resveratrol however warrant further investigation in glaucoma patients. Studies of these antioxidants and other nutrients could create adjunctive or alternative preventative and treatment modalities for glaucoma to those currently available.

[Role of the Blood-Retinal Barrier Transporters: Antiaging in Retina].

Since the retina continuously receives light to enable vision, reactive oxygen species (ROS) are easily generated in neural retina. The oxidative stress induced by ROS may be involved in the onset and progression of blinding aging diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Although supply of antioxidants to the retina is important to maintain the redox homeostasis in neural retina, the blood-retinal barrier (BRB) is created by complex tight-junctions of retinal capillary endothelial cells and retinal pigment epithelial cells to prevent the free diffusion of substances. The BRB is equipped with several membrane transporters to supply nutrients and essential molecules including antioxidants and drugs which exhibit antiaging effect to the retina from the circulating blood. In this review, the transporter-mediated retinal distribution of key endogenous compounds and drugs, such as vitamin C, l-cystine and gabapentin, is introduced for antiaging of the retina.

Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma.

Optic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.

Reported evidence of vitamin E protection against cataract and glaucoma.

Cataract and glaucoma are the major causes of severe visual loss and blindness in older adults. This review article describes the currently available basic and clinical evidence regarding vitamin E protection against these eye diseases in the chronologic order of the publications. Experimental evidence has suggested both that oxidative stress due to the accumulation of free radicals plays a role in the pathogenesis of cataracts and glaucoma and that the process can be prevented or ameliorated by vitamin E. The results of observational studies have been inconsistent regarding the association between blood vitamin E levels and the risk of age-related cataract or glaucoma. Despite the encouraging effects of vitamin E from case series, case-control studies, and cross-sectional studies in humans, the effects on cataract formation and/or progression have not been consistent among prospective and randomized control studies; few randomized control studies have tested the effects of supplemental vitamin E on glaucoma development or progression. Given the high prevalence of cataract and glaucoma in the elderly population, even a modest reduction in the risk for these eye diseases would potentially have a substantial public health impact; however, the potential benefits of vitamin E on cataract or glaucoma remain inconclusive and need to be carefully considered.

1α,25-dihydroxyvitamin D3 protects retinal ganglion cells in glaucomatous mice.

BACKGROUND: Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice). METHODS: DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA. RESULTS: DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF. CONCLUSIONS: 1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.

Presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino / Preoperative intraocular pressure for the control of primary angle closure treated with clear lens extraction

Introducción: la extracción del cristalino transparente en pacientes con cierre angular primario se plantea si existe presión intraocular mayor o igual que 30 mm Hg o daño por glaucoma. En ojos con elevación moderada de la presión intraocular se desconocen los resultados. Objetivo: evaluar la influencia de la presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino transparente. Material y Métodos: se realizó un estudio pre-experimental, entre enero de 2013 y enero de 2020, incluyó 78 ojos de 78 pacientes con cierre angular primario tratados con extracción del cristalino transparente; divididos en dos grupos según presión intraocular preoperatoria. Para el análisis estadístico se empleó chi cuadrado de independencia, probabilidad exacta de Fisher, prueba t para muestras independientes y análisis de varianza de medidas repetidas; con significación estadística del 95 por ciento. Resultados: hubo diferencias significativas entre ambos grupos para longitud axial (p=0,003), grosor del cristalino (p<0,001) y espesor corneal central (p=0,016). La presión intraocular y número de colirios, variaron de forma muy significativa (p<0,001) entre el pre y posoperatorio, y entre ambos grupos en los diferentes momentos analizados. En el grupo A el 94,4 por ciento de los ojos mostró control absoluto posoperatorio invariable en el tiempo, en el grupo B la mayoría de los ojos tuvo control relativo con diferencias muy significativas (p<0,001) entre ambos. Conclusiones: la presión intraocular preoperatoria influye en el control del cierre angular primario tratado con extracción del cristalino transparente; valores previos menores que 30 mm Hg, propician mejor control posoperatorio(AU)

Introduction: Clear lens extraction is considered in patients older than 50 years with primary angle closure and intraocular pressure greater than or equal to 30 mm Hg or damage due to glaucoma. The results are unknown in eyes with a moderate elevation of intraocular pressure. Objective: To evaluate the influence of preoperative intraocular pressure in the control of the primary angle closure treated with clear lens extraction. Material and Methods: A pre-experimental study was conducted between January 2013 and January 2020. It included a total of 78 eyes of 78 patients with primary angle closure treated with clear lens extraction. They were divided into two groups according to preoperative intraocular pressure. For statistical analysis, Chi-square test, Fisher's exact probability test, and t test were used for independent samples and analysis of variance with repeated measurements; with 95 percent statistical significance. Results: There were significant differences in axial length (p=0,003), lens thickness (p<0,001) and central corneal thickness (p=0,016) between both groups. Intraocular pressure and the number of eye drops varied very significantly (p<0,001) between the pre-and postoperative periods and between both groups at the different moments analyzed. In group A, 94,4 percent of the eyes showed absolute postoperative control, which remained unchanged over time. In group B, most eyes had relative control. There were very significant differences (p<0,001) between both groups. Conclusions: Preoperative intraocular pressure influences the control of primary angle closure treated with clear lens extraction; previous values less than 30 mm Hg favor better postoperative control(AU)

Neuroprotection of the Inner Retina Also Prevents Secondary Outer Retinal Pathology in a Mouse Model of Glaucoma.

Purpose: We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also prevents outer retinal changes. Methods: We used an established microbead occlusion model of glaucoma whereby intraocular pressure (IOP) was elevated. Specific antibodies were used to label rod and cone bipolar cells (BCs), horizontal cells (HCs), and retinal ganglion cells (RGCs), as well as synaptic components in control and glaucomatous eyes, to assess structural damage and cell loss. ERG recordings were made to assess outer retina function. Results: We found structural and functional damage of BCs, including significant cell loss and dendritic/axonal remodeling of HCs, following IOP elevation. The first significant loss of both BCs occurred at 4 to 5 weeks after microbead injection. However, early changes in the dendritic structure of RGCs were observed at 3 weeks, but significant changes in the rod BC axon terminal structure were not seen until 4 weeks. We found that protection of inner retinal neurons in glaucomatous eyes by pharmacological blockade of gap junctions or genetic ablation of connexin 36 largely prevented outer retinal damage. Conclusions: Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.

Influence of Trace Elements on Neurodegenerative Diseases of The Eye-The Glaucoma Model.

Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated. In this review, we aimed to summarize the current evidence on the role of trace elements in the pathogenesis and prevention of glaucomatous diseases. Special attention is also paid to the genetic background associated with glaucoma-related abnormalities of physiological processes that regulate or involve the ions of elements considered as trace elements necessary for the functioning of the cells.

Melatonin Prevents Non-image-Forming Visual System Alterations Induced by Experimental Glaucoma in Rats.

Glaucoma is a blindness-causing disease that involves selective damage to retinal ganglion cells (RGCs) and their axons. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system functions, such as pupillary light reflex and circadian rhythms. We analyzed the effect of melatonin on the non-image-forming visual system alterations induced by experimental glaucoma. For this purpose, male Wistar rats were weekly injected with vehicle or chondroitin sulfate into the eye anterior chamber. The non-image-forming visual system was analyzed in terms of (1) melanopsin-expressing RGC number, (2) anterograde transport from the retina to the olivary pretectal nucleus and the suprachiasmatic nuclei, (3) blue- and white light-induced pupillary light reflex, (4) light-induced c-Fos expression in the suprachiasmatic nuclei, (5) daily rhythm of locomotor activity, and (6) mitochondria in melanopsin-expressing RGC cells. Melatonin prevented the effect of experimental glaucoma on melanopsin-expressing RGC number, blue- and white light-induced pupil constriction, retina-olivary pretectal nucleus, and retina- suprachiasmatic nuclei communication, light-induced c-Fos expression in the suprachiasmatic nuclei, and alterations in the locomotor activity daily rhythm. In addition, melatonin prevented the effect of glaucoma on melanopsin-expressing RGC mitochondrial alterations. These results support that melatonin protected the non-image-forming visual system against glaucoma, probably through a mitochondrial protective mechanism.

Protection of retinal ganglion cells in glaucoma: Current status and future.

Glaucoma is a neuropathic disease that causes optic nerve damage, loss of retinal ganglion cells (RGCs), and visual field defects. Most glaucoma patients have no early signs or symptoms. Conventional pharmacological glaucoma medications and surgeries that focus on lowering intraocular pressure are not sufficient; RGCs continue to die, and the patient's vision continues to decline. Recent evidence has demonstrated that neuroprotective approaches could be a promising strategy for protecting against glaucoma. In the case of glaucoma, neuroprotection aims to prevent or slow down disease progression by mitigating RGCs death and optic nerve degeneration. Notably, new pharmacologic medications such as antiglaucomatous agents, antibiotics, dietary supplementation, novel neuroprotective molecules, neurotrophic factors, translational methods such as gene therapy and cell therapy, and electrical stimulation-based physiotherapy are emerging to attenuate the death of RGCs, or to make RGCs resilient to attacks. Understanding the roles of these interventions in RGC protection may offer benefits over traditional pharmacological medications and surgeries. In this review, we summarize the recent neuroprotective strategy for glaucoma, both in clinical trials and in laboratory research.

Long Non-coding RNA MALAT1 Alleviates the Elevated Intraocular Pressure (Eiop)-induced Glaucoma Progression via Sponging miR-149-5p.

Background: Glaucoma is an optic neuropathic disease and contributed to the irreversible blindness caused by the slow death of retinal ganglion cells (RGCs). Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be aberrantly expressed in diverse diseases, including glaucoma. However, the mechanism of MALAT1 in glaucoma was still undefined.Methods: The levels of MALAT1, microRNA-149-5p (miR-149-5p) in RGCs cultured under elevated pressure were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The putative target of MALAT1 was predicted by starBase v2.0 online database, and dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were performed to verify this interaction. The cell viability of RGCs was measured by Cell Counting Kit-8 (CCK-8) assay. The apoptotic rate was evaluated via flow cytometry. The protein levels of apoptosis-related proteins (Bax, B-cell lymphoma 2 (Bcl-2)) and Cleaved caspase 3 were assessed by Western blot.Results: The level of MALAT1 was significantly down-regulated, and the level of miR-149-5p was distinctly up-regulated in RGCs under pressure in a dose-dependent manner. Functionally, MALAT1 overexpression or miR-149-5p inhibitor alleviated the inhibitory effect on cell viability and the promoted effect on apoptotic rate of RGCs in EIOP. The interaction between MALAT1 and miR-149-5p was predicted by starBase v2.0 online database, and dual luciferase reporter assay, RIP assay and RNA pull-down assay validated the interaction. Combined with the loss and gain experiment results, miR-149-5p was negatively interacted with MALAT1. Furthermore, miR-149-5p mimics mitigated the promoted impact on cell viability and the suppressive impact on apoptotic rate by targeting MALAT1.Conclusion: MALAT1 promoted cell proliferation and inhibited cell apoptosis of RGCs via targeting miR-149-5p in glaucoma in vitro, which might shed light on the mechanism of glaucoma pathogenesis.

Prophylactic anti-glaucoma therapy in dogs with primary glaucoma: A practitioner survey of current medical protocols.

AIM: To examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians. METHODS: A survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection. RESULTS: Responses from 199 veterinary ophthalmology clinicians were evaluated. While a large variety of topical anti-hypertensive drugs and protocols were used, the most commonly used medications were aqueous humor production suppressors such as dorzolamide 2.0% ophthalmic solution, timolol 0.5% ophthalmic solution, and a combination product containing both drugs. Latanoprost 0.005% ophthalmic solution was used infrequently for prophylaxis by comparison. The majority of respondents do not use concurrent anti-inflammatory medications (61.22%), although a sizeable minority used prednisolone acetate, dexamethasone, or ketorolac as prophylactic treatment. Systemically administered ocular anti-hypertensive agents were rarely used. Only 40% of respondents used neuroprotectant agents; the most commonly prescribed were the calcium channel blocker amlodipine and the nutraceutical Ocu-Glo™. Recommended intervals between re-examination by the clinician ranged from one month to one year, with most re-evaluations occurring every 3 to 6 months. The majority of respondents recommended more frequent assessments of IOP at intervals between once monthly and once every 3 months. CONCLUSIONS: Data analysis of medical therapy for the normotensive fellow eye of dogs previously diagnosed with primary glaucoma suggests that there is a great need for well-designed, prospective, controlled, multi-center studies to determine which protocols have the greatest efficacy in delaying an overt attack in the previously normotensive eye in dogs with a genetic predisposition to glaucoma. Prospective studies utilizing a carbonic anhydrase inhibitor such as dorzolamide and a prostaglandin analogue such as latanoprost would be reasonable as these two drugs are widely used in the treatment of overt glaucoma and would allow for an exploration of the impact of different mechanisms of action of lowering IOP on the pathophysiology of primary glaucoma.