Background: Retinal endothelial cells are very active and contribute to the integrity of the neurovascular unit. Vascular dysfunction has been proposed to contribute to the pathogenesis of glaucoma. Here, we evaluated the hypothesis that ocular hypertension triggers mitochondrial alterations in endothelial cells impairing the integrity of the blood retinal barrier (BRB).
Methods: Ocular hypertension was induced by injection of magnetic microbeads into the anterior chamber of EndoMito-EGFP mice, a strain expressing green fluorescent protein selectively in the mitochondria of endothelial cells. Capillary density, mitochondrial volume, and the number of mitochondrial components were quantified in 3D-reconstructed images from whole-mounted retinas using Imaris software. Dynamin-related protein (DRP-1), mitofusin-2 (MFN-2) and optic atrophy-1 (OPA-1) expression were assessed by western blot analysis of enriched endothelial cells. Mitochondrial structure was evaluated by transmission electron microscopy (TEM) and oxygen consumption rate was monitored by Seahorse analysis. The integrity of the BRB was evaluated by quantifying Evans blue leakage.
Results: Our data demonstrate that two and three weeks after ocular hypertension induction, the total mitochondria volume in endothelial cells decreased from 0.140±0.002 μm3 from non-injured retinas to 0.108±0.005 and 0.093±0.007 μm3, respectively in glaucomatous eyes (mean ± S.E.M, ANOVA, P<0.001; N=6/group). Frequency distribution showed a substantial increase of smaller mitochondria complexes (<0.5 μm3) in endothelial cells from glaucomatous retinas. Significant upregulation of DRP-1 was found in vessels isolated from glaucomatous retinas compared to the intact retinas, while MFN-2 and OPA-1 expression was not affected. Structural alteration in endothelial cell mitochondria was confirmed by TEM, which were accompanied by a 1.93-fold reduction in the oxygen consumption rate as well as 2.6-fold increase in vasculature leakage in glaucomatous retinas (n=3–6/group). In addition, this model did not trigger changes in the density of the vascular network, suggesting that mitochondrial fragmentation was not due to endothelial cell loss.
Conclusions: This study shows that ocular hypertension leads to early alterations in the dynamic of endothelial cell mitochondria, contributing to vascular dysfunction in glaucoma.
Background: Pericytes are contractile cells that wrap along the walls of capillaries. In the brain, pericytes play a crucial role in the regulation of capillary diameter and vascular blood flow in response to metabolic demand. The contribution of pericytes to microvascular deficits in glaucoma is currently unknown. To address this, we used two-photon excitation microscopy for longitudinal monitoring of retinal pericytes and capillaries in a mouse glaucoma model.
Methods: Ocular hypertension was induced by injection of magnetic microbeads into the anterior chamber of albino mice expressing red fluorescent protein selectively in pericytes (NG2-DsRed). Minimally invasive, multiphoton imaging through the sclera of live NG2-DsRed mice was used to visualize pericytes and capillary diameter at one, two and three weeks after glaucoma induction. In vivo fluctuations in pericyte intracellular calcium were monitored with the calcium indicator Fluo-4. Ex vivo stereological analysis of retinal tissue prior to and after injection of microbeads was used to confirm our in vivo findings.
Results: Live two-photon imaging of NG2-DsRed retinas demonstrated that ocular hypertension induced progressive accumulation of intracellular calcium in pericytes. Calcium uptake correlated directly with the narrowing of capillaries in the superficial, inner, and outer vascular plexuses (capillary diameter: na?ve control =4.7±0.1 μm, glaucoma =4.0±0.1 μm, n=5–6 mice/group, Student’s t-test P<0.05). Frequency distribution analysis showed a substantial increase in the number of small-diameter capillaries (≤3 μm) and a decrease in larger-diameter microvessels (≥5–9 μm) at three weeks after induction of ocular hypertension (n=5–6 mice/group, Student’s t-test P<0.05).
Conclusions: Our data support two main conclusions. First, two-photon excitation microscopy is an effective strategy to monitor longitudinal changes in retinal pericytes and capillaries in live animals at glaucoma onset and progression. Second, ocular hypertension triggers rapid intracellular calcium increase in retinal pericytes leading to substantial capillary constriction. This study identifies retinal pericytes as important mediators of early microvascular dysfunction in glaucoma.
Abstract: Complications of myopia have become an important public health issue with serious socio-economic burdens. Prevention and treatment are both important. The Taiwan Student Vision Care Program (TSVCP) promoted by Ministry of Education (MOE) has been carried out for 3 decades in Taiwan. The myopia prevalence has increased rapidly to a high level and therefore myopia prevention has continued to be the most important item in the program. Therefore, TSVCP aims to decrease the prevalence of myopia, in order to decrease the high myopia related blindness in the future. Recently, outdoor activity has been found to be an important protective factor for myopia and was implemented in TSVCP since 2010. Afterwards, the nationwide vision impairment rate (uncorrected vision 20/25 or less) of elementary school students declined unprecedentedly and continuously in recent years. Evidence-based protective and risk factors for myopia are now clearer. Widespread acknowledgement of myopic disease, preventing the onset of myopia, prompt diagnosis, and early treatment to control progression are all important.
Abstract: Pathologic myopia is the major cause of the loss of the best-corrected visual acuity (BCVA) worldwide, especially in East Asian countries. The loss of BCVA is caused by the development of myopic macula patchy, myopic traction macula patchy, and myopic optic neuropathy (or glaucoma). The development of such vision-threatening complications is caused by eye deformity, characterized by a formation of posterior staphyloma. The recent advance in ocular imaging has greatly facilitated the clarification of pathologies and pathogenesis of pathological myopia and myopia-related complications. These technologies include ultra-wide field fundus imaging, swept-source optical coherence tomography, and 3D MRI. In addition, the new treatments such as anti-VEGF therapies for myopic choroid all neovascularization have improved the outcome of the patients. Swept-source OCT showed that some of the lesions of myopic maculopathy were not simply chorioretinal atrophy but were Bruch’s membrane holes. Features of myopic traction maculopathy have been analyzed extensively by using OCT. The understanding the pathophysiology of complications of pathologic myopia is considered useful for better management of this blinding eye disease.
Abstract: Corneal blindness represents one of the world’s three major causes of blindness, and the fundamental problem of corneal transplantation is a severe shortage of donor tissues worldwide, resulting in approximately 1.5 million new cases of blindness annually. To address the growing need for corneal transplants two main approaches are being pursued: allogenic and bioengineering cornea. Bioengineering corneas are constructed by naturally generating an extracellular matrix (ECM) component as the scaffold structure with or without corneal cells. It is well established that the scaffold structure directs the fate of cells, therefore, the fabrication of the correct scaffold structure components could produce an ideal corneal substitute, able to mimic the native corneal function. Another key factor in the construction of tissue engineering cornea is seed cells. However, unlike the epithelium and stroma cells, human cornea endothelium cells (HCECs) are notorious for having a limited proliferative capacity in vivo because of the mitotic block at the G1 phase of the cell cycle due to “contact-inhibition”. This review will focus on the main concepts of recent progress towards the scaffold and seed cells, especially endothelial cells for bioengineering cornea, along with future perspectives.
Abstract: The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.
Background: To investigate and analyze the hospitalization costs of inpatients with primary acute angle closure glaucoma (PACG), and to explores the influencing factors of hospitalization cost and to provide reference for specialized hospitals to carry out clinical pathways.
Methods: The first page diagnostic data of PACG patients’ medical records were collected, and an Excel database was established according to the International Classification of Diseases (ICD-10) code. Statistical analysis of hospitalization data was performed using SPSS 17.0 software.
Results: Hospitalization days and clinical pathway which affect the change of the hospitalization cost (P<0.001).
Conclusions: Hospitalization day is an important factor affecting the hospitalization cost, reducing unnecessary hospitalization time can control the increase of hospitalization cost.
Abstract: Contrast is the differential luminance between one object and another. Contrast sensitivity (CS) quantifies the ability to detect this difference: estimating contrast threshold provides information about the quality of vision and helps diagnose and monitor eye diseases. High contrast visual acuity assessment is traditionally performed in the eye care practice, whereas the estimate of the discrimination of low contrast targets, an important complementary task for the perception of details, is far less employed. An example is driving when the contrast between vehicles, obstacles, pedestrians, and the background is reduced by fog. Many conditions can selectively degrade CS, while visual acuity remains intact. In addition to spatial CS, “temporal” CS is defined as the ability to discriminate luminance differences in the temporal domain, i.e., to discriminate information that reaches the visual cortex as a function of time. Likewise, temporal sensitivity of the visual system can be investigated in terms of critical fusion frequency (CFF), an indicator of the integrity of the magnocellular system that is responsible for the perception of transient stimulations. As a matter of fact, temporal resolution can be abnormal in neuro-ophthalmological clinical conditions. This paper aims at considering CS and its application to the clinical practice.
