Development Of Retinal Vascular Diseases Research Articles

Does SarsCoV-2 infection really cause damage to retinal microcirculation in mild cases of COVID-19?

Aim To evaluate changes of retinal microcirculation in mild cases of recovered COVID-19 patients at least three months after the infection by optical coherence tomography angiography (OCTA) non-invasive method. Methods In this prospective cross-sectional study, 50 right eyes of 50 recovered COVID-19 patients were compared with 50 right eyes of age and gender-matched healthy controls. After the complete ophthalmological examination, all participants underwent OCTA measurements (RTVue XR Avanti, Optovue, Fremont, CA, USA). Results The time between the initial onset of symptoms, and ophthalmologic examination was 479.20 ±197.10 (126-754) days. Findings of ophthalmic examination of all eyes of the recovered COVID-19 patients were within normal range. Significantly reduced superficial (p=0.046) and deep (p=0.044) macular vessel density (VD) in foveal region in the eyes of the recovered COVID-19 patients was found compared with healthy controls. Significantly enlarged foveal avascular zone (FAZ) area and perimeter in the eyes of the recovered COVID-19 patients (p<0.001) were found too. Conclusion Recovered COVID-19 patients have impaired retinal microcirculation, which can be a cause of the development of retinal vascular diseases.

IL-17 signaling induces iNOS+ microglia activation in retinal vascular diseases.

Activation of microglia and inflammation-mediated vascular damages are suggested to play a decisive role in the pathogenesis of various retinopathies. The inducible nitric oxide synthase (iNOS) was required for activated microglia-mediated injuries. However, the induction mechanism of microglia activation during retinal vascular diseases is still elusive. Here we showed that IL-17 induced microglia activation with high expression of iNOS and promoted the development of retinal vascular diseases. IL-17-dependent activation of the STAT3-iNOS pathway was essentially required for microglia activation, which promoted endothelial cell growth and accelerated vascular leakage and leukostasis via IL-6 in vitro and in vivo. Taken together, our data provide novel mechanistic insights on microglia activation-mediated retinopathy, unveil the specific role of IL-17 on microglia, and define novel therapeutic targets for treating retinal vascular diseases.

Photoreceptor responses to light in the pathogenesis of diabetic retinopathy.

Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of retinal illumination on photoreceptor metabolism, effects of light modulation on the severity of diabetic retinopathy, and recent clinical trials testing the treatment of diabetic retinopathy with interventions that impact photoreceptor metabolism. Finally, we introduce several possible mechanisms that could link photoreceptor responses to light and the development of retinal vascular disease in diabetes. Collectively, these concepts form the basis for a growing body of investigative efforts aimed at developing novel pharmacologic and nonpharmacologic tools that target photoreceptor physiology to treat a very common cause of blindness across the world.

Предикторы формирования сосудистой ретинальной патологии у женщин после преэклампсии

Предикторы формирования сосудистой ретинальной патологии у женщин после преэклампсии

Do photoreceptor cells cause the development of retinal vascular disease?

The retinal vasculature is affected in a number of clinically important retinopathies, including diabetic retinopathy. There has been a considerable amount of research into the pathogenesis of retinal microvascular diseases, but the potential contribution of the most abundant cell population in the retina, photoreceptor cells, has been largely overlooked. This review summarizes ongoing research suggesting that photoreceptor cells play a critical role in the development of retinal vascular disease in diabetic retinopathy and other retinopathies.

Ocular Manifestations of Systemic Diseases: The Eyes are the Windows of the Body

An ocular manifestation of a systemic disease is an eye condition that directly or indirectly results from a disease process originating from another part of the body. There are many diseases known to cause ocular or visual changes as a result of systemic disease. Diabetes, for example, is the leading cause of new cases of blindness in those aged 20-74, with ocular manifestations such as diabetic retinopathy and macular edema affecting up to 80% of those who have had the disease for 15 years or more. Other diseases such as acquired immunodeficiency syndrome (AIDS) and hypertension are commonly found to have associated ocular symptoms. Physicians need to consider that systemic disease can involve the eyes and it is important for ophthalmologists to understand that they may be the first to suggest a diagnosis due to underlying systemic disease. According to the quote “The eyes are the windows of the soul”, ophthalmologists should view the eyes as not only windows of the soul but also a window to the physical state of the entire body. Systemic hypertension is a major risk factor for the development of retinal vascular diseases including hypertensive retinopathy, retinal vein or artery occlusion, and embolic events. High blood pressure also increases the risk for the development and progression of diabetic retinopathy. Signs of hypertensive retinopathy are predictive of target-organ damage including cardiovascular and cerebrovascular diseases [1]. High blood pressure affects the heart, kidney, brain, large arteries, and also the eyes. Retinal, choroidal, and optic nerve circulations undergo pathophysiological changes resulting in clinical signs referred to as hypertensive retinopathy, hypertensive choroidopathy, and hypertensive optic neuropathy. Systemic hypertension also increases the risk for the development of retinal vein and artery occlusion, retinal-arteriolar emboli, and diabetic retinopathy. Diabetic retinopathy is one of the common causes of blindness. It is an ocular manifestation of diabetes, which affects up to 80 percent of all patients who have had diabetes for 20 years or more. Diabetic macular edema is the most common cause of visual dimness in patients with diabetic retinopathy. Dr. Lee will discuss the challenges and current treatments to prevent the visual disturbance related to diabetic macular edema [2]. Systemic lupus erythematosus (SLE) is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body. SLE is a potentially life-threatening multisystem disease that is commonly associated with ocular manifestations. The purpose of this review is to outline the ocular manifestations of SLE and treatments [3]. Ocular complications have been reported in up to one-third of patients with SLE. Ocular manifestations can be associated with significant morbidity and eye issues may play a role as a marker for systemic disease activity. Keratoconjunctivitis sicca is the most common ocular problem in patients with SLE. When ophthalmologists see patients complaining of dry eye symptoms, determining the underlying reason as to why these patients are suffering from dry eye symptoms is important. The hypo-secretion of tears is one cause of dry eye symptoms.

Homocysteine Inhibition of Endothelium-Dependent Nitric Oxide-Mediated Dilation of Porcine Retinal Arterioles via Enhanced Superoxide Production

Elevated plasma concentration of homocysteine, a sulfur-containing amino acid, is an emerging risk factor for cardiovascular diseases. Recent epidemiologic studies have confirmed that elevated homocysteine levels are associated with ocular vascular diseases; however, the direct effect of homocysteine on ocular microvascular reactivity remains unknown. We investigated whether homocysteine affects endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the homocysteine-mediated effect. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Diameter changes were recorded using videomicroscopy techniques. Intraluminal treatment with homocysteine (1 mM, 180 minutes) significantly attenuated arteriolar dilation in response to the endothelium-dependent NO-mediated agonists bradykinin and A23187 but not in response to the endothelium-independent NO donor sodium nitroprusside. In the presence of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the nicotinamide adenine dinucleotide phosphate-oxidase (NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, and peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone, the detrimental effect of homocysteine on bradykinin-induced dilation was prevented; however, neither the xanthine oxidase inhibitor allopurinol, the JNK inhibitor SP600125, or pioglitazone with PPAR-γ inhibitor GW9662 had that effect. Homocysteine inhibits endothelium-dependent NO-mediated dilation in the retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase. By impairing endothelium-dependent NO-mediated vasoreactivity, homocysteine potentially facilitates development of retinal vascular diseases. In addition, pioglitazone can prevent homocysteine-induced endothelial dysfunction possibly by activating PPAR-γ.

C-Reactive Protein Inhibits Endothelium-Dependent Nitric Oxide-Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production

Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, clinical studies have implicated that elevated CRP is an independent risk factor for diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP on ocular microvascular reactivity remains unknown. The authors examined whether CRP can affect endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the CRP-mediated effect. Porcine retinal arterioles (internal diameter, 71 +/- 2 microm) were isolated and pressurized without flow for in vitro study. Diameter changes were recorded using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production. Intraluminal treatment with a clinically relevant concentration of CRP (7 microg/mL, 60 minutes) significantly attenuated arteriolar dilation to endothelium-dependent NO-mediated agonists bradykinin and A23187 but not to endothelium-independent NO donor sodium nitroprusside. In the presence of superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, simvastatin, or Rho-kinase inhibitor Y-27632, the detrimental effect of CRP on bradykinin-induced dilation was prevented. DHE staining showed that CRP produced TEMPOL-sensitive superoxide production in the arteriolar endothelium. CRP inhibits endothelium-dependent NO-mediated dilation in retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase and RhoA/Rho-kinase activation. By impairing endothelium-dependent NO-mediated vasoreactivity, CRP can potentially facilitate the development of retinal vascular diseases. In addition, statins are beneficial by preserving endothelial function, possibly through inactivation of the RhoA/Rho-kinase pathway.

Microvascular metabolism in diabetes

Hyperglycemia has been implicated in the development of retinal vascular disease. Consequently, the effects of excessive hexose concentration on cells of the vascular wall are receiving increasing attention. Techniques for isolating metabolically active microvessels from tissues such as those from the retina and cerebral cortex are providing new opportunities for the study of the uptake and metabolism of hexose by microvessels. Such studies indicate that hexose uptake by microvessels is not insulin dependent and that microvessels are capable of metabolizing hexose by pathways common to many diverse tissues, including anaerobic and aerobic glycolysis, pentose phosphate shunt, and glycogenogenesis. Microvessels isolated from diabetic animals metabolize glucose at a subnormal rate. Hexitol production and accumulation has been implicated in the pathogenesis of diabetic complications in a variety of tissues and might also play a role in the development of diabetic microvascular disease. We have quantitated hexitol-producing metabolic activity of retinal and cerebral microvessels isolated from dogs, a species known to develop a retinopathy similar to that seen in diabetic patients. Erythrocytes were removed by perfusion prior to microvessel isolation because they are known to have hexitol-producing activity. Both retinal and cerebral microvessels produce galactitol from galactose, and this activity is inhibited in the presence of the aldose reductase inhibitor sorbinil. The presence of hexitol-producing activity within microvessels is consistent with a possible role of polyol production in the etiology of diabetic microvascular disease. Nevertheless, it is not even clear that the primary defect leading to vascular disease in diabetes resides in the vasculature itself; nonvascular cells such as erythrocytes, platelets, and glial cells have been postulated to play a role in the development of the vascular lesions. The steps linking diabetic retinopathy to hyperglycemia await clarification.