scholarly journals Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head

2021 ◽  
Vol 15 ◽  
Author(s):  
Jing Hong Loo ◽  
Ying Shi Lee ◽  
Chang Yi Woon ◽  
Victor H. K. Yong ◽  
Bingyao Tan ◽  
...  

Glaucoma is a neurodegenerative disease, which results in characteristic visual field defects. Intraocular pressure (IOP) remains the main risk factor for this leading cause of blindness. Recent studies suggest that disturbances in neurovascular coupling (NVC) may be associated with glaucoma. The resultant imbalance between vascular perfusion and neuronal stimulation in the eye may precede retinal ganglion cell (RGC) loss and increase the susceptibility of the eye to raised IOP and glaucomatous degeneration. Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found abundantly in retinal glial and vascular tissues, with possible involvement in regulating the neurovascular coupling response. Mutations in Cav-1 have been identified as a major genetic risk factor for glaucoma. Therefore, we aim to evaluate the effects of Cav-1 depletion on neurovascular coupling, retinal vessel characteristics, RGC density and the positive scotopic threshold response (pSTR) in Cav-1 knockout (KO) versus wild type C57/Bl6 mice (WT). Following light flicker stimulation of the retina, Cav-1 KO mice showed a smaller increase in perfusion at the optic nerve head and peripapillary arteries, suggesting defective neurovascular coupling. Evaluation of the superficial capillary plexus in Cav-1 KO mice also revealed significant differences in vascular morphology with higher vessel density, junction density and decreased average vessel length. Cav-1 KO mice exhibited higher IOP and lower pSTR amplitude. However, there was no significant difference in RGC density between Cav-1 KO and wild type mice. These findings highlight the role of Cav-1 in regulating neurovascular coupling and IOP and suggest that the loss of Cav-1 may predispose to vascular dysfunction and decreased RGC signaling in the absence of structural loss. Current treatment for glaucoma relies heavily on IOP-lowering drugs, however, there is an immense potential for new therapeutic strategies that increase Cav-1 expression or augment its downstream signaling in order to avert vascular dysfunction and glaucomatous change.

2016 ◽  
Vol 61 (2) ◽  
pp. 164-186 ◽  
Author(s):  
Daniele Prada ◽  
Alon Harris ◽  
Giovanna Guidoboni ◽  
Brent Siesky ◽  
Amelia M. Huang ◽  
...  

2021 ◽  
Vol 7 (2) ◽  
pp. 195-199
Author(s):  
Helen Rosita J ◽  
Gnanaselvan J ◽  
Amudhavadivu S ◽  
Anna Kurian Mullasseril

Glaucoma is the leading cause of irreversible blindness, one of the risk factor recognised being high myopia. Intra ocular pressure may be normal in myopic patients, with optic nerve head glaucoma characteristics. Eye ball elongation and optic nerve head tilting may be present in patients with high myopia that will represent field defects mimicking glaucoma. Treating patients with myopia having suspected aspects of glaucoma may be a challenge but even more challenging is the diagnosis of glaucoma in myopic patients.: To evaluate the association of glaucoma features with myopia. To create the awareness regarding the long term follow up.: Patients in the age group of 15 to 45 years who had attended our institution over a period of one year who fulfilled the inclusion and exclusion criteria were subjected for this study. Fifty four patients who were diagnosed to have moderate or high degree myopia were selected for this analytical study. They were subjected to vision, ocular examination, tonometry and results obtained were analysed.: In our study moderate myopes constituted 55.5% and high myopes were 44.5%. The mean Intra ocular pressure and the mean corrected Intra ocular pressure in high myopes were observed to be higher than in moderate myopia. It was observed that higher prevalence of glaucoma was observed in high myopes.: There is a clinically as well as statistically significant difference between mean Intra ocular pressure and mean corrected Intra ocular pressure. So mean corrected Intra ocular pressure should be measured .From our study, there is a clear indication that there is increased prevalence of glaucoma in high myopes.


2021 ◽  
Author(s):  
Sophie Pilkinton ◽  
T.J. Hollingsworth ◽  
Brian Jerkins ◽  
Monica M. Jablonski

Glaucoma is a multifactorial, polygenetic disease with a shared outcome of loss of retinal ganglion cells and their axons, which ultimately results in blindness. The most common risk factor of this disease is elevated intraocular pressure (IOP), although many glaucoma patients have IOPs within the normal physiological range. Throughout disease progression, glial cells in the optic nerve head respond to glaucomatous changes, resulting in glial scar formation as a reaction to injury. This chapter overviews glaucoma as it affects humans and the quest to generate animal models of glaucoma so that we can better understand the pathophysiology of this disease and develop targeted therapies to slow or reverse glaucomatous damage. This chapter then reviews treatment modalities of glaucoma. Revealed herein is the lack of non-IOP-related modalities in the treatment of glaucoma. This finding supports the use of animal models in understanding the development of glaucoma pathophysiology and treatments.


2017 ◽  
Vol 27 (4) ◽  
pp. 485-490 ◽  
Author(s):  
Antonio Longo ◽  
Teresio Avitabile ◽  
Maurizio G. Uva ◽  
Vincenza Bonfiglio ◽  
Andrea Russo ◽  
...  

Purpose To evaluate the morphology of optic nerve head by spectral-domain optical coherence tomography (SD-OCT) in patients with unilateral central retinal vein occlusion (CRVO). Methods In 39 consecutive patients with unilateral CRVO and 39 healthy controls, morphologic parameters of optic nerve head were assessed in both eyes by Spectralis SD-OCT using a custom radial B-scan pattern. The length of Bruch membrane opening (BMO) was measured in OCT scans, and optic disc diameters (DD) were assessed in infrared fundus photographs. Axial length was determined by IOLMaster. Results The BMO length was measured in all eyes with CRVO, while DD was not assessed in 9 eyes (27.3%) that had undefined disc margins. Compared to healthy controls (mean BMO length 1,511 ± 79 μm, mean disc diameter 1,521 ± 77 μm), in eyes with CRVO with defined disc margins (n = 28 [71.8%]), no significant difference was found in BMO length and DD (1,473 ± 118 μm and 1,516 ± 104 μm, respectively). Eyes with CRVO with undefined disc margins had lower BMO length (1,289 ± 61 μm [-14.7%], p = 0.001); also, in fellow eyes, these patients had lower BMO length and DD. In all groups, no significant difference was seen between BMO and DD. A correlation was found between axial length and BMO length and disc diameter (both p<0.001) Conclusions Most of the eyes with CRVO had normal optic disc diameter, but about 25% of patients with CRVO have reduced optic disc dimensions.


2021 ◽  
Vol 13 ◽  
pp. 251584142199538
Author(s):  
Hilal Kılınç Hekimsoy ◽  
Ali Mehmet Şekeroğlu ◽  
Ali Mert Koçer ◽  
Vedat Hekimsoy ◽  
Ali Akdoğan

Objectives: To investigate the optical coherence tomography angiography (OCTA) parameters of the optic nerve head and peripapillary retina and to assess macular and peripapillary retinal nerve fiber layer (RNFL) thickness by using spectral-domain optical coherence tomography (SD-OCT) in patients with limited scleroderma and to compare these results with those of healthy control subjects. Materials and Methods: 42 patients with a confirmed diagnosis of limited scleroderma and 32 age- and sex-matched healthy control subjects were included in the study. OCTA was performed for the radial peripapillary capillary plexus (RPCP) whole image, inside disc, and peripapillary vessel densities in all participants with XR Avanti AngioVue OCTA (Optovue, Fremont, California, USA). OCT images were obtained with Spectralis OCT with eye-tracking dual-beam technology (Heidelberg Engineering GmbH, Heidelberg, Germany), and peripapillary RNFL thickness was evaluated with circle program. The data from the right eyes of all participants were used for statistical analysis. Results: No significant difference was found between the radial RPCP whole image, inside disc, and peripapillary vessel density values or the RNFL parameters of the scleroderma patients when compared with the controls ( p > 0.05 for all). Conclusion: Decreased peripapillary vessel density on OCTA, which can be an early sign of glaucoma, could not be observed in scleroderma patients in this study. However, further long-term studies are still needed to identify glaucoma tendency in patients with scleroderma before clinically detectable glaucoma.


2000 ◽  
Vol 279 (3) ◽  
pp. H970-H975 ◽  
Author(s):  
Steven R. Lentz ◽  
Rochelle A. Erger ◽  
Sanjana Dayal ◽  
Nobuyo Maeda ◽  
M. René Malinow ◽  
...  

Hyperhomocysteinemia is a risk factor for stroke, myocardial infarction, and venous thrombosis. Moderate hyperhomocysteinemia is associated with impaired endothelial function, but the mechanisms responsible for endothelial dysfunction in hyperhomocysteinemia are poorly understood. We have used genetic and dietary approaches to produce hyperhomocysteinemia in mice. Heterozygous cystathionine β-synthase-deficient mice (CBS +/−), which have a selective defect in homocysteine transsulfuration, and wild-type (CBS +/+) littermates were fed either a control diet or a diet that is relatively deficient in folic acid for 6 wk. Plasma total homocysteine was 5.3 ± 0.7 μM in CBS +/+ mice and 6.4 ± 0.6 μM in CBS +/− mice ( P = 0.3) given the control diet. Plasma total homocysteine was 11.6 ± 4.5 μM in CBS +/+ mice and 25.1 ± 3.2 μM in CBS +/− mice ( P = 0.004) given a low-folate diet. In mice fed the control diet, relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine did not differ significantly between CBS +/+ mice and CBS +/− mice. In contrast, in mice fed a low-folate diet, maximal relaxation to acetylcholine was markedly impaired in CBS +/− mice (58 ± 9%) compared with CBS +/+ mice (84 ± 4%) ( P = 0.01). No differences in relaxation to the endothelium-independent vasodilator sodium nitroprusside were observed among the four groups of mice. These data indicate that CBS-deficient mice are predisposed to hyperhomocysteinemia during dietary folate deficiency, and moderate hyperhomocysteinemia is associated with marked impairment of endothelial function in mice.


2021 ◽  
Author(s):  
Thanadet Chuangsuwanich ◽  
Tin Aung Tun ◽  
Xiaofei Wang ◽  
Zhi Yun Chin ◽  
Satish Kumar Panda ◽  
...  

Purpose: To assess optic nerve head (ONH) deformations and strains during adduction, abduction, and intraocular pressure (IOP) elevation in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Design: Clinic-based cross-sectional study. Participants: 114 HTG subjects and 114 NTG subjects. Methods. We recruited 228 subjects (114 subjects with HTG [pre-treatment IOP > 21mmHg] and 114 with NTG [pre-treatment IOP < 21mmHg]). For each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degree adduction, (3) 20 degree abduction, and (4) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the prelaminar tissue (PLT), the choroid, the sclera and the lamina cribrosa (LC) using a deep learning algorithm. We also digitally aligned the OCT volumes obtained from (2)-(4) to the primary gaze volume (1) before performing digital volume correlation (DVC) analysis to quantify IOP- and gaze-induced ONH tissues three-dimensional displacements and effective strain (a local measure of tissue deformation) for all scenarios. Main Outcome Measures: Three-dimensional ONH displacements and strains. Results: Across all subjects, adduction generated high effective strain (4.2 +- 1.4%) in the ONH tissues with no significant difference (p>0.05) with those induced by IOP elevation (4.5 +- 1.5%); while abduction generated significantly lower (p = 0.014) effective strain (3.8 +- 1.1%). Interestingly, the LC of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG:4.6 +- 1.7% vs NTG:4.1 +- 1.5%, p = 0.047). Conversely, the LC tissue of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9 +- 1.9% vs HTG: 4.0 +- 1.4%, p = 0.041). Conclusion: We found that adduction produced comparable strains and displacements as IOP elevation. We also found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects - and that these differences were most pronounced in the LC tissue.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Nauphar ◽  
T M Pratamawati ◽  
M E Sanif

Abstract Introduction Rheumatic heart disease (RHD) is a chronic condition causing damage in cardiac valvular tissues due to acute rheumatic fever (ARF) post Streptococcus pyogenes or Group A β hemolytic Streptococcus (GABHS) infection. The damage to the valve tissue within the heart can lead to congestive heart failure, strokes, endocarditis, and death. However, only 3–6% of post-streptococcal infection individuals develop ARF, suggesting host susceptibility in the pathogenesis of ARF. Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) may be linked to the genetic susceptibility of the host that results in abnormal autoimmune response to the infection. Purpose This study aims to look at MTHFR A1298C polymorphism as a risk factor for rheumatic heart disease in Indonesian population. Methods This was an observational analytical study with case control approach. Blood samples were obtained from 36 Indonesian RHD patients with confirmed diagnosis of RHD using echocardiography and 36 healthy controls. Patients DNA were isolated and then amplified using polymerase chain reaction followed by restriction fragment length polymorphism analysis using MboII restriction enzyme. Results We observed a significant difference between genotypic distribution between cases and controls (OR = 4.6, 95% CI = 1.697–12.469, p=0.002). The genotype frequency of MTHFR A1298C AA (wild type) was 36.1%, heterozygous AC was 47.2%, and 16.7% of CC in the cases group. In the control group, the genotype frequency of the wild type AA was 72.2%, AC was 27.8%, and homozygous CC was 2.8%. Conclusion Compared with the CC frequency in the control population, the frequency of MTHFR CC was 5 times higher in individuals with rheumatic heart disease (p=0.002), suggesting that MTHFR A1298C gene variant may contribute to the pathogenesis of RHD. Individuals with MTHFR 1298C have a risk of 4.6 times higher to develop ARF post streptococcal infection.


2018 ◽  
Vol 103 (3) ◽  
pp. 374-378 ◽  
Author(s):  
Masoud Aghsaei Fard ◽  
Sasan Moghimi ◽  
Alireza Sahraian ◽  
Robert Ritch

BackgroundEnlargement of optic disc cupping is seen both in glaucoma and in neurological disorders. We used enhanced depth imaging with spectral-domain optical coherence tomography to differentiate glaucoma from non-glaucomatous optic neuropathy.MethodsThe optic discs were scanned in this prospective comparative study, and the lamina cribrosa (LC) thickness and anterior laminar depth (ALD) in the central, superior and inferior optic nerve head, and peripapillary choroidal thicknesses, were measured.ResultsThere were 31 eyes of 31 patients with severe glaucoma and 33 eyes of 19 patients with non-glaucomatous cupping. Eyes of 29 healthy controls were also enrolled. There was no significant difference in the cup-to-disc ratio and in the average peripapillary nerve fibre layer thickness between the glaucoma and non-glaucomatous cupping groups (p>0.99). The average peripapillary choroidal thickness was thinner in glaucoma eyes than in the control eyes after adjusting for age and axial length. Glaucomatous and non-glaucomatous eyes had greater ALD and thinner LC than the control eyes (p<0.001 for both). ALDs of glaucoma eyes were deeper than non-glaucomatous eyes (p=0.01 for central ALD) when age, axial length and peripapillary choroidal thickness were included in the linear mixed model. Prelaminar thickness and LC thickness of glaucoma eyes were not different from non-glaucomatous eyes after adjusting.ConclusionDeeper ALD was observed in glaucoma than non-glaucomatous cupping after adjusting for choroidal thickness.


2021 ◽  
Author(s):  
Ozge SARAC ◽  
Yelda Y TASCI ◽  
Nilufer YESILIRMAK ◽  
Ozlem UNAL ◽  
Semih ONER ◽  
...  

Abstract Purpose: The purpose of the study is to evaluate the efficacy of ultrasound elastography (USE) in differentiating optic disc drusen (ODD) from optic disc edema (ODE) and to investigate the relationship between corneal biomechanics and optic nerve elasticity. Methods: This prospective, clinical study included 28 eyes of 16 ODD patients (Group 1), 23 eyes of 18 ODE patients (Group 2) and 30 eyes of 15 healthy controls (Group 3). Best corrected distance visual acuity (BDVA), corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), Goldmann-correlated IOP (IOPg) and optic nerve head (ONH)-elasticity were measured. Results: The mean BDVA value was significantly lower in Group 2 compared to Groups 1 and 3 (p<0.001), there was no significant difference between Groups 1 and 3 (p=0.089). The mean intraconal fat to ONH ratio was significantly higher in Group 1 compared to Group 2 (p=0.008) and 3 (p=0.002), there was no significant difference between Group 2 and 3 (p=0.182). The receiver operating characteristic curve areas for ONH-elasticity in differentiating group 1 and group 2 was 0.728 (p=0.008) with 80% sensitivity and 60% specificity when the cut-off point was set at 2.29. Corneal biomechanics (CH, CRF, IOPcc, IOPg) were not different between the three groups (p>0.05), however there was a significant correlation between corneal and ONH biomechanics in drusen group (p<0.05). Conclusion: The evaluation of the ONH with USE seems to provide useful data in differentiating ODD from ODE. Significant correlation was revealed between corneal and ONH biomechanics in drusen group.


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