Association of Skin Intrinsic Fluorescence with Retinal Microvascular Complications of Long Term Type 1 Diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy

Klein, Barbara E. K.; Horak, Kayla; Maynard, John; Lee, Kristine E.

doi:10.1080/09286586.2016.1269934

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…35% of the Joslin Medalists and 16% of participants in the Canadian Study of Longevity in Type 1 Diabetes) [30,82]. The role of long-term excess glycaemic exposure (and the formation of AGEs) has been clear from multiple experimental sources [83], including the Joslin Medalist Study that found higher levels of plasma carboxyethyl lysine and pentosidine but not traditional markers of glycaemic exposure (discussed above in the context of renal injury) also associated with the presence of retinopathy [30]. In that same study, individuals free of retinopathy appeared to be at minimal risk of progression [30]; the forces of selection may explain this so it is important that clinicians consider the appropriate risk factor modification for prevention of incidence and progression of complications at any age or duration.…”

Section: Retinopathy and Macular Oedemamentioning

confidence: 99%

Discoveries from the study of longstanding type 1 diabetes

et al. 2021

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Award programmes that acknowledge the remarkable accomplishments of long-term survivors with type 1 diabetes have naturally evolved into research programmes to determine the factors associated with survivorship and resistance to chronic complications. In this review, we present an overview of the methodological sources of selection bias inherent in survivorship research (selection of those with early-onset diabetes, incidence-prevalence bias and bias from losses to follow-up in cohort studies) and the breadth and depth of literature focusing on this special study population. We focus on the learnings from the study of longstanding type 1 diabetes on discoveries about the natural history of insulin production loss and microvascular complications, and mechanisms associated with them that may in future offer therapeutic targets. We detail descriptive findings about the prevalence of preserved insulin production and resistance to complications, and the putative mechanisms associated with such resistance. To date, findings imply that the following mechanisms exist: strategies to maintain or recover beta cells and their function; activation of specific glycolytic enzymes such as pyruvate kinase M2; modification of AGE production and processing; novel mechanisms for modification of renin-angiotensin-aldosterone system activation, in particular those that may normalise afferent rather than efferent renal arteriolar resistance; and activation and modification of processes such as retinol binding and DNA damage checkpoint proteins. Among the many clinical and public health insights, research into this special study population has identified putative mechanisms that may in future serve as therapeutic targets, knowledge that likely could not have been gained without studying long-term survivors.

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Section: Retinopathy and Macular Oedemamentioning

confidence: 99%

Discoveries from the study of longstanding type 1 diabetes

et al. 2021

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“…DR mainly causes vision loss and blindness in adults worldwide (Chong et al, 2017;Klein, 2007;Cheung et al, 2010). The incidence of DR has been increasing annually worldwide (Wang et al, 2012;Klein et al, 2017). Laser photocoagulation treatment shows no significant improvement in visual acuity in the long term (Liu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

MiR-542-5p regulates the progression of diabetic retinopathy by targeting CARM1

Guo

Nulahou

et al. 2020

Acta Biochim Pol

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Diabetic retinopathy (DR), as the most frequent microvascular complication of diabetes mellitus (DM), causes vision loss and blindness in adults worldwide with increasing incidence. MicroRNAs (miRNAs) are involved in the regulation of DR. However, the role of miR-542-5p is still unknown. Here, we demonstrate that miR-542-5p is down-regulated in patients with DR and in high-glucose (HG)-treated retinal pigment epithelial cells. Moreover, miR-542-5p overexpression inhibits apoptosis in retinal pigment epithelial cells exposed to HG. The interaction between miR-542-5p and co-activator-associated arginine methyltransferase 1 (CARM1) is confirmed. MiR-542-5p mimics decrease the CARM1 level and miR-542-5p inhibitor increases the CARM1 level. Additionally, CARM1 overexpression promotes the miR-542-5p-mediated apoptosis in HG-treated retinal pigment epithelial cells. In summary, the data suggest that miR-542-5p may suppress apoptosis in retinal pigment epithelial cells via targeting CARM1, which provides a new therapeutic target for the treatment of patients with DR.

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“…Diabetic retinopathy (DR) is considered to be among the most severe causes of vision impairment and loss in the working-aged and elderly population [1], and the incidence of DR increases annually worldwide [2][3][4][5]. Due to the complex etiology of DR and other factors, the pathogenesis of DR is not entirely clear [6].…”

Section: Introductionmentioning

confidence: 99%

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Fan

Zhang

et al. 2019

IJMS

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The aim of the study was to demonstrate how transthyretin (TTR) could affect long non-coding RNA (lncRNA) of maternally expressed gene 3 (MEG3) and play important roles in diabetic retinopathy (DR). A DR model in C57BL/6 mice was established after intraperitoneal injection of streptozotocin (STZ). After intravitreal injection with TTR pAAV vector, MEG3 short hairpin RNA (shRNA), scrambled shRNA, or MEG3, retinal imaging, retinal trypsin digestion, and fundus vascular permeability tests were performed. Cell counting kit-8 (CCK8), transwell, and Matrigel assays were employed to detect the proliferation and migration of human retinal microvascular endothelial cells (hRECs). The binding between long non-coding RNA of maternally expressed gene 3 (lncRNA-MEG3) and microRNA-223-3p (miR-223-3p) was observed by using luciferase reporter assays, while co-immunoprecipitation (co-IP) was employed to confirm the interaction between TTR and the target. In the DR mice model, retinal vascular leakage and angiogenesis were repressed by overexpressing TTR. In vitro, the added TTR promoted the level of lncRNA-MEG3 by interacting with poly (A) binding protein cytoplasmic 1 (PABPC1), and then repressed proliferation and angiogenesis of hRECs. In vivo, silencing or overexpressing lncRNA-MEG3 significantly affected retinal vascular phenotypes. Additionally, the interaction between lncRNA-MEG3 and miR-223-3p was confirmed, and silencing of miR-223-3p revealed similar effects on hRECs as overexpression of lncRNA-MEG3. In summary, in the DR environment, TTR might affect the lncRNA MEG3/miR-223-3p axis by the direct binding with PABPC1, and finally repress retinal vessel proliferation.Keywords: diabetic retinopathy (DR); transthyretin (TTR); long non-coding RNA (lncRNA); maternally expressed gene 3 (MEG3); polyadenylate-binding protein cytoplasmic 1 (PABPC1) Int.In the eyes, transthyretin (TTR) is mainly expressed in human retinal pigment epithelial cells (hRPECs) and the choroid [7], and it usually works as the carrier of thyroxine (T4) and retinol [8,9]. As previously reported, TTR should be correlated with diabetes-associated diseases, e.g., type I diabetes patients showed lower serum TTR levels [10]. In clinical investigations, myopia was revealed to protect diabetic patients from suffering DR [11,12]. Our previous work has demonstrated that higher vitreous TTR content of high myopia patient [13] might help to prevent the progression of DR [14]. The serum and vitreous TTR levels in DR patients were associated with DR progression [15]; TTR suppressed angiogenesis by affecting the angiopoietin-Tie signaling pathway in hyperglycemia [16], and enhanced the apoptosis of hRECs through a hypoxia-associated 78-kDa glucose-regulated protein (GRP78)-dependent pathway [17]. Still, the regulatory mechanisms involving TTR in DR are not entirely clear.Long non-coding RNAs (lncRNAs) regulate targeted mRNA expression via the microRNA (miRNA) response element known as competing endogenous RNA (ceRNA) [18,19]. LncRNAs are known to play vital roles in oc...

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Association of Skin Intrinsic Fluorescence with Retinal Microvascular Complications of Long Term Type 1 Diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy

Cited by 9 publications

References 27 publications

Discoveries from the study of longstanding type 1 diabetes

Discoveries from the study of longstanding type 1 diabetes

MiR-542-5p regulates the progression of diabetic retinopathy by targeting CARM1

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

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