Assessment of Retinal Blood Flow in Diabetic Retinopathy Using Doppler Fourier-Domain Optical Coherence Tomography

Srinivas, Sowmya; Tan, Ou; Nittala, Muneeswar Gupta; Wu, Jennifer L.; Fawzi, Amani A.; Huang, David; Sadda, Srinivas R.

doi:10.1097/iae.0000000000001479

Cited by 29 publications

(30 citation statements)

References 33 publications

(62 reference statements)

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“…In our experiments with the retina of diabetic mice, cellular coupling, vasomotor response and blood flow were impaired. This is consistent with reduced flicker response and abnormal blood flow in the retina of diabetic patients 53–55 . As we showed in a mouse model of diabetic retinopathy, expression of the Cx43 GJ along the vascular relay is preferentially downregulated 6, 13 .…”

Section: Discussionsupporting

confidence: 83%

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Dynamic connectivity maps of pericytes and endothelial cells mediate neurovascular coupling in health and disease

Kovács-Öller

Ivanova

Bianchimano

et al. 2019

Preprint

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21 22 Highlights 24 25  Within a structurally symmetric mosaic, pericytes form discriminatory connections 26 27  Pericyte connectome tunes with a precision matching a neuronal receptive field 28 29  Focal but not global input evokes a vasomotor response by strengthening the gap-junction 30 mediated signaling towards a feeding vascular branch 31 32  Disrupted functional connectivity map triggers loss of the functional hyperemia in diabetic 33 neuropathy 34 3 Summary 35 36Functional hyperemia, or matching blood flow to activity, is spatially accurate to direct the oxygen and 37 nutrients to regionally firing neurons. The underlying signaling mechanisms of neurovascular coupling 38 remain unclear, but are critical for brain function and establish the diagnostic power of BOLD-fMRI. 39Here, we described a mosaic of pericytes, the vasomotor capillary cells in the living retina. We then 40 tested if this symmetric net of pericytes and surrounding neuroglia predicted a connectivity map in 41 response to sensory stimuli. Surprisingly, we found that these connections were not only discriminatory 42 across cell types, but also highly asymmetric spatially. First, pericytes connected predominantly to other 43 neighboring pericytes and endothelial cells, and less to arteriolar smooth muscle cells, and not to 44 surrounding neurons or glia. Second, focal, but not global stimulation evoked a directional vasomotor 45 response by strengthening connections along the feeding vascular branch. This activity required local 46 NO signaling and occurred by means of direct coupling via gap-junctions. By contrast, bath application 47 of NO or diabetes, a common microvascular pathology, not only weakened the vascular signaling but 48 also abolished its directionality. We conclude that the discriminatory nature of neurovascular 49 interactions may thus establish spatial accuracy of blood delivery with the precision of the neuronal 50 receptive field size, and is disrupted early in microvascular disease. 51 52 53 56 57 Local changes in neural activity evoke a vascular response that is spatially restricted to the activated 58 region. The ubiquitous nature of the microvasculature and the diversity of routes through which blood 59 can be distributed make this task challenging. Furthermore, blood perfusion must be shifted or 60 expanded to accommodate for changing activity patterns. To accomplish changes in demand, 61 functional hyperemia must involve at least three events with a spatial precision that enables 62 discrimination of the active site from its resting neighbor: 1) sensing local changes, 2) transmission of 63 vasoactive signals along the supplying vascular branch, culminating in 3) vasomotor response that 64 directs blood to the active region. The mechanisms responsible for this spatial accuracy are not clear, 65 but are critical for brain function and establish the diagnostic power and precision of BOLD-fMRI 1 . 66 67The strategic location of capillaries within synaptic layers where neurotransmitters are released, 68 supports thei...

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Section: Discussionsupporting

confidence: 83%

“…In diabetes, vascular pathology is associated with high glucose, causing activation of protein kinase C pathway 49–51 and reduced activity of Cx43 6, 12, 27, 52, 53 . In our experiments with the retina of diabetic mice, cellular coupling, vasomotor response and blood flow were impaired.…”

Section: Discussionmentioning

confidence: 99%

Dynamic connectivity maps of pericytes and endothelial cells mediate neurovascular coupling in health and disease

Kovács-Öller

Ivanova

Bianchimano

et al. 2019

Preprint

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“…Doppler OCT provides information about the three-dimensional anatomy of the retina and also Doppler shift of reflected light from vascular structures, which is used to evaluate BF. [ 5 51 ]…”

Section: Doppler Fourier-domain Optical Coherence Tomographymentioning

confidence: 99%

“…[ 1 ] Vascular impairment contributes to the development of various ophthalmic diseases including age-related macular degeneration, diabetic retinopathy (DR), and glaucoma. [ 2 3 4 5 6 ] As a result, there have been continuous efforts to develop reliable and reproducible methods for assessing BF. Due to the challenge involved in quantifying BF in various tissues of the eye, many techniques have been devised for the evaluation of ocular hemodynamics.…”

mentioning

confidence: 99%

Evaluating ocular blood flow

Maram

Srinivas

Sadda

2017

Indian J Ophthalmol

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Studies have shown that vascular impairment plays an important role in the etiology and pathogenesis of various ocular diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal venous occlusive disease. Thus, qualitative and quantitative assessment of ocular blood flow (BF) is a topic of interest for early disease detection, diagnosis, and management. Owing to the rapid improvement in technology, there are several invasive and noninvasive techniques available for evaluating ocular BF, with each of these techniques having their own limitations and advantages. This article reviews these important techniques, with a particular focus on Doppler Fourier domain optical coherence tomography (OCT) and OCT-angiography.

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“…With regard to DR, vascular relay physiological drivers are particularly sensitive to hyperglycemia, leading to detectable changes in very early stages of disease onset. Indeed, early DR has been implicated in the abnormal activation of Protein Kinase C (Lee et al, 1989;Williams & Schrier, 1993;Shibata et al, 2019) and the reduced connectivity of Cx43 gap-junctions (Oku et al, 2001;Sato et al, 2002;Bobbie et al, 2010;Srinivas et al, 2017).…”

Section: Role For Pericytes In Drmentioning

confidence: 99%

Of neurons and pericytes: The neuro-vascular approach to diabetic retinopathy

2020

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Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus and an increasingly common cause of visual impairment. Blood vessel damage occurs as the disease progresses, leading to ischemia, neovascularization, blood–retina barrier (BRB) failure and eventual blindness. Although detection and treatment strategies have improved considerably over the past years, there is room for a better understanding of the pathophysiology of the diabetic retina. Indeed, it has been increasingly realized that DR is in fact a disease of the retina’s neurovascular unit (NVU), the multi-cellular framework underlying functional hyperemia, coupling neuronal computations to blood flow. The accumulating evidence reveals that both neurochemical (synapses) and electrical (gap junctions) means of communications between retinal cells are affected at the onset of hyperglycemia, warranting a global assessment of cellular interactions and their role in DR. This is further supported by the recent data showing down-regulation of connexin 43 gap junctions along the vascular relay from capillary to feeding arteriole as one of the earliest indicators of experimental DR, with rippling consequences to the anatomical and physiological integrity of the retina. Here, recent advancements in our knowledge of mechanisms controlling the retinal neurovascular unit will be assessed, along with their implications for future treatment and diagnosis of DR.

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Assessment of Retinal Blood Flow in Diabetic Retinopathy Using Doppler Fourier-Domain Optical Coherence Tomography

Abstract: Total retinal blood flow was significantly lower in eyes with severe NPDR and PDR compared with normal eyes. Retinal blood flow determined by Doppler OCT may be a useful parameter for evaluating patients with DR.

Cited by 29 publications

References 33 publications

Dynamic connectivity maps of pericytes and endothelial cells mediate neurovascular coupling in health and disease

Dynamic connectivity maps of pericytes and endothelial cells mediate neurovascular coupling in health and disease

Evaluating ocular blood flow

Of neurons and pericytes: The neuro-vascular approach to diabetic retinopathy

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