Diabetic mice have retinal and choroidal blood flow deficits and electroretinogram deficits with impaired responses to hypercapnia

Purpose The purpose of this study was to investigate neuronal and vascular functional deficits in the retina and their association in a diabetic mouse model. We measured electroretinography (ERG) responses and choroidal and retinal blood flow (ChBF, RBF) with magnetic resonance imaging (MRI) in healthy and diabetic mice under basal conditions and under hypercapnic challenge. Methods Ins2Akita diabetic (Diab, n = 8) and age-matched, wild-type C57BL/6J mice (Ctrl, n = 8) were studied under room air and moderate hypercapnia (5% CO2). Dark-adapted ERG a-wave, b-wave, and oscillatory potentials (OPs) were measured for a series of flashes. Regional ChBF and RBF under air and hypercapnia were measured using MRI in the same mice. Results Under room air, Diab mice had compromised ERG b-wave and OPs (e.g., b-wave amplitude was 422.2±10.7 μV in Diab vs. 600.1±13.9 μV in Ctrl, p < 0.001). Under hypercapnia, OPs and b-wave amplitudes were significantly reduced in Diab (OPs by 30.3±3.0% in Diab vs. -3.0±3.6% in Ctrl, b-wave by 17.9±1.4% in Diab vs. 1.3±0.5% in Ctrl). Both ChBF and RBF had significant differences in regional blood flow, with Diab mice having substantially lower blood flow in the nasal region (ChBF was 5.4±1.0 ml/g/min in Diab vs. 8.6±1.0 ml/g/min in Ctrl, RBF was 0.91±0.10 ml/g/min in Diab vs. 1.52±0.24 ml/g/min in Ctrl). Under hypercapnia, ChBF increased in both Ctrl and Diab without significant group difference (31±7% in Diab vs. 17±7% in Ctrl, p > 0.05), but an increase in RBF was not detected for either group. Conclusions Inner retinal neuronal function and both retinal and choroidal blood flow were impaired in Diab mice. Hypercapnia further compromised inner retinal neuronal function in diabetes, while the blood flow response was not affected, suggesting that the diabetic retina has difficulty adapting to metabolic challenges due to factors other than impaired blood flow regulation.

Choroidal thickness and choriocapillaris vascular density in myopic anisometropia

Background This study aims to examine interocular differences in the choroidal thickness and vascular density of the choriocapillaris in anisometropic myopes and to further explore the relationship between choroidal blood flow and myopia. Methods The sample comprised 44 participants with anisometropic myopia, aged 9 to 18 years, with normal best-corrected visual acuity. All participants underwent a series of examinations, including spherical equivalent refraction (SER) and axial length (AL), measured by a Lenstar optical biometer and optical coherence tomography angiography (OCTA) scanner. OCT measured the choroidal thickness, vascular density, and flow voids of the choriocapillaris, and a customized algorithm was implemented in MATLAB R2017a with the post-correction of AL. The choroidal thickness was measured at the fovea and 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm nasally, temporally, inferiorly, and superiorly to the fovea. The vascular density and the flow voids of the choriocapillaris were measured at a 0.6-mm-diameter central circle, and the 0.6–2.5 mm diameter circle in the nasal, temporal, inferior, and superior regions. Repeated-measured ANOVAs were used to analyze the interocular differences. Partial correlations with the K value and age adjustments were used to study the relationships between the choroidal thickness, the choriocapillaris vascular density and flow voids, the SER and AL. Results The choroidal thickness of the more myopic eyes was significantly thinner than less myopic eyes (P ≤ 0.001), and the flow voids in the more myopic eyes were more than less myopic eyes (P = 0.002). There was no significant difference in the vascular density of the choriocapillaris between the more and less myopic eyes (P = 0.525). However, when anisometropia was more than 1.50 D, the vascular density of choriocapillaris in the more myopic eyes was significantly less than the less myopic eyes (P = 0.026). The interocular difference of the choroidal thickness was significantly correlated with the interocular difference in SER and AL in the center, superior, and inferior regions but not in the nasal or temporal regions. The interocular differences of the vascular density and the flow voids of the choriocapillaris were not correlated with the interocular difference of SER and AL. Conclusions The choroidal thickness is thinner in the more myopic eyes. The flow void is increased, and the vascular density of the choriocapillaris is reduced in the more myopic eyes of children with anisometropia exceeding 1.50 D.

Effect of Dual Endothelin Receptor Antagonist on a Retinal Degeneration Animal Model by Regulating Choroidal Microvascular Morphology

Objective. Clinical studies have found that increasing levels of plasma endothelin-1 (ET-1) might inhibit choroidal blood flow (BF) and promote choroidal vasoconstriction. This study was designed to investigate ET-1 levels and its effect on choroidal microvascular morphology in a retinitis pigmentosa (RP) animal model. Methods. Mice with retinal degeneration (rd10) were intragastrically administered bosentan, a dual endothelin receptor antagonist. We detected plasma ET-1 levels using an enzyme-linked immunosorbent assay (ELISA) kit at P14, P21, and P28 and evaluated ET-1 expression in RPE/choroid/sclera complexes using western blot and whole mount immunofluorescence staining at P28. Retinal thickness was measured using hematoxylin and eosin (H&E) staining at P28. At the same time, we also estimated choroidal microvascular densities using vascular luminal casting with a scanning electron microscope (SEM). Results. Plasma ET-1 levels were increased significantly in rd10 mice at P21 (65.48 ± 24.83 pg/ml) and P28 (85.89 ± 20.23 pg/ml) compared with C57BL/6J mice at P21 (33.52 ± 16.33 pg/ml) and P28 (42.38 ± 17.53 pg/ml); the expression of ET-1 was also upregulated in RPE/choroid/sclera complexes at P28. Bosentan inhibited ET-1 expression in plasma ( P < 0.05 ) and RPE/choroid/sclera complexes at P28 in rd10 mice. Choroidal microvascular densities were decreased in rd10 mice, and bosentan could weaken these changes. Conclusion. Plasma and local ET-1 was elevated in an animal model of RP, suggesting that it likely participates in the pathological progression of retinal degeneration and may thus provide a new intervention target. ET-1 blockade might exert its protective effect by elevating choroidal microvascular density via inhibition of ET-1.

Ischemic Choroidal Diseases

Introduction Ischemic choroidal diseases are an underdiagnosed entity. The clinical pattern varies according to the size and the localisation of the affected vascular structure. Clinical Presentation In eyes with occlusion of the long posterior ciliary arteries, characteristic triangular patches of choroidal ischemia (Amalric sign) are seen, which in the course of time merge into well-defined areas of atrophy of the retinal pigment epithelium. Above the non-perfused choroidal areas, hyperpigmented, grouped lines appear (Siegrist streaks). Circumscribed ischemia of smaller choroidal arterioles and capillary vessels appears as multifocal, yellowish lesions in the posterior fundus (Elschnig spots). Vortex vein occlusion becomes manifest as exudative haemorrhagic choroidal swelling in the periphery. Causes of Choroidal Ischemia Apart from arterial hypertension as a major risk factor, some immunological disorders such as giant cell arteritis and systemic lupus erythematosus and haematological pathologies also affect choroidal perfusion. Furthermore, choroidal ischemia occurs due to local inflammation, as found in eyes with acute multifocal posterior placoid pigment epitheliopathy (APMPPE). Rarely, choroidal infarction is of iatrogenic origin or drug-induced. Recent advances in imaging, such as the introduction of enhanced depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A), have improved the visualisation of the choroidal vasculature and complement the classical angiographic procedures. In patients with age-related macular degeneration (AMD) and diabetes, some changes in choroidal blood flow and vascular structure have also been noted. While in AMD the choroidal pathologies correlate with the disease progression and the functional prognosis, the pathophysiological relationship between diabetic choroidopathy and retinopathy is currently unclear. Management and Conclusion With regard to the limited therapeutic options for choroidal ischemia, optimisation of the cardiovascular risk profile and the management of accompanying ocular and systemic diseases are essential.

Correlation of choriocapillaris hemodynamic data from dynamic indocyanine green and optical coherence tomography angiography

To investigate the correlation between posterior pole choroidal blood flow evaluated with digital subtraction indocyanine green angiography and enface optical coherence tomography angiography (OCTA). Imaging in animal study. The anatomy of 2 cynomogulus monkeys was studied. Each monkey was given a 0.75 mg/kg injection of indocyanine green in the saphenous vein. The dynamic angiographic filling sequence was recorded at 15 frames per second using the Heidelberg Spectralis. After image registration, sequential frame subtraction was used to image the dye front moving through the choroid. The OCTA was obtained by frame averaging nine separate choriocapillaris slab flow images obtained from the Zeiss Plex Elite 9000. Posterior pole choriocapillaris filling pattern in relation to the choriocapillaris anatomy as imaged by OCTA. In the posterior pole, the choriocapillaris fills in the pattern of discrete units with variable sizes and shapes. The cycle of dye filling begins in the peripapillary area and progresses toward the periphery in a wavelike manner. This filling pattern repeats in a cyclical manner, consistent with the cardiac cycle. OCTA shows a uniform mesh of vessels. While OCTA shows a uniform meshwork appearance of the choriocapillaris, the dynamic dye angiography suggests an irregular configuration of functional units partitioned by pressure gradients as opposed to structural boundaries. Disturbance of local perfusion pressure within choroidal vasculature may result in abnormal flow patterns, which could be evaluated in the clinic using commercially available equipment.

Ocular Blood Flow Abnormalities and Their Correlation with Body Mass Index in Obese Patients

PurposeTo evaluate the effects of obesity on ocular blood flow including choroidal thickness and retrobulbar blood flow values in comparison with healthy subjectsMethodsThe 102 eyes of 102 female patients were included in this prospective study.Color Doppler ultrasonography (CDU) was used to evaluate the retrobulber vessels.Choroidal thickness was measured by using the optical coherence tomography (OCT). ResultsThere was a significant difference in IOP values within the groups with the highest values in group 3 and the lowest in group 1.There was also a positive correlation between BMI and IOP. The CT was found to be statistically significantly lower in group 2 and group 3 than in the control group at all measurement points. The choroidal thickness was also statistically significantly lower in group 3 than in group 2 at the subfoveal, nasal 500 µm, and the temporal 500 and 1000 µm measurement points.The mean CRA PSV and EDV values were lower in group 2 and group 3 than in group 1, while group 3 had the lowest mean CRA PSV value among the groups. When compared to group 1, the OA EDV value was lower only in group 3 while the OA PSV value was statistically significantly lower in group 3 than in both group 2 and group 1. There was no significant difference between the groups in terms of RI and PI.ConclusionsObesity can create a predisposition to ocular pathologies both by increasing the IOP and decreasing the retrobulbar and choroidal blood flow.

Nitric Oxide Interaction with the Eye

Nitric oxide (NO) is acknowledged as a vital intercellular messenger in multiple systems in the body. Medicine has focused on its functions and therapeutic applications for decades, especially in cardiovascular and nervous systems, and its role in immunological responses. This review was composed to demonstrate the prevalence of NO in components of the ocular system, including corneal cells and multiple cells in the retina. It discussed NO’s assistance during the immune, inflammation and wound-healing processes. NO is identified as a vascular endothelial relaxant that can alter the choroidal blood flow and prompt or suppress vascular changes in age-related macular degeneration and diabetes, as well as the blood supply to the optic nerve, possibly influencing the progression of glaucoma. It will provide a deeper understanding of the role of NO in ocular homeostasis, the delicate balance between overproduction or underproduction and the effect on the processes from aqueous outflow and subsequent intraocular pressure to axial elongation and the development of myopia. This review also recognized the research and investigation of therapies being developed to target the NO complex and treat various ocular diseases.