Angiopoietin-2-related modulation of retinal angiogenesis – A new model for diabetic retinopathy

Abstract Introduction: Angiopoietin-2 (ANGPT-2) is a member of a growth factor family that binds to the endothelial receptor tyrosine kinase 2 and regulates vascular development and function. Under hyperglycemic conditions, ANGPT-2 is upregulated and leads to vascular destabilization, pericyte dropout, and aggravation of inflammation. In this context, studies have reported the involvement of ANGPT-2 in the pathogenesis of diabetic retinopathy (DR). Thus, polymorphisms in ANGPT-2 gene may be of interest in this field. Objective: To investigate the association between the rs2442598 polymorphism in the ANGPT-2 gene and DR. Methods: This case-control study comprised 107 patients with type 1 diabetes mellitus (T1DM) and DR (cases) and 129 patients with T1DM without DR (controls) and with ≥10 years of DM. The ANGPT-2 rs2442598 (G/A) polymorphism was genotyped by real-time PCR using TaqMan MGB probes. Results: Genotype distributions of this polymorphism were consistent with Hardy-Weinberg Equilibrium. Frequency of the rs2442598 A allele was higher in cases compared to controls (P= 0.011). Moreover, the A/A genotype was higher in cases than controls (P= 0.017) and was associated with risk for DR after adjustment for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and presence of hypertension (OR= 5.19, IC95% 1.21 - 22.27). This association was maintained under the recessive (OR= 4.78, IC95% 1.14 - 19.99) and additive (OR= 6.861, IC95% 1.45 - 32.38) inheritance models. Conclusion: Our data demonstrate, for the first time, the association of the ANGPT-2 rs2442598 A allele with risk for DR in T1DM patients from Southern Brazil.

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Deficiency in nucleoside diphosphate kinase B aggravates the development of diabetic retinopathy through up-regulation of angiopoietin-2

Diabetologie und Stoffwechsel ◽

10.1055/s-0034-1375096 ◽

2014 ◽

Vol 9 (S 01) ◽

Author(s):

Y Qiu ◽

D Zhao ◽

EY Skolnik ◽

HP Hammes ◽

T Wieland ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Nucleoside Diphosphate Kinase ◽

Nucleoside Diphosphate Kinase B ◽

Angiopoietin 2

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Combination Approaches Targeting Neurodegeneration, Oxidative stress and Inflammation in the Treatment of Diabetic Retinopathy

Current Drug Targets ◽

10.2174/1389450122666210319113136 ◽

2021 ◽

Vol 22 ◽

Author(s):

Siddhi Dilip Chalke ◽

Pravin Popatrao Kale

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Vision Loss ◽

Treatment Options ◽

Treatment Strategies ◽

Early Stages ◽

Advanced Stages ◽

Severe Vision Loss ◽

Angiopoietin 2 ◽

Endothelial Growth Factor

: Diabetic Retinopathy (DR) is one of the most severe ocular problems of diabetes. It is a microvascular complication that impairs the vision of diabetic individuals and can cause acquired blindness. Currently available treatment options like laser therapy, vitrectomy, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and glucocorticoids help to reduce vision loss at advanced stages. In spite of the available therapies, patients with severe vision loss face difficulty in achieving normal vision. There is a need for development of newer treatment strategies to address the condition from the early stages. Multiple factors owing to complex pathophysiological events are responsible for this long-term complication. Neurodegeneration, inflammation, and oxidative stress are the three important factors associated with the development of DR. Oxidative stress is a major contributor to the onset and progression of DR. Pathological events like retinal neurodegeneration and inflammation damage the retina right in the early stages of DR. Different combinations of treatments targeting these pathological events are discussed in the present review. The first combination discussed is citicoline and resveratrol. The second combination is duloxetine and N-acetyl cysteine (NAC). These combinations may help in the early stages of DR. CD5-2 and angiopoietin-2 inhibitors is the third combination. This combination may help to manage diabetic macular edema. The main purpose of this article is to discuss the link between these pathologies and the three combination approaches with the objective of consideration of newer therapeutic approaches in research related to DR treatment.

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Angiopoietin-2 plays an important role in retinal angiogenesis

Journal of Cellular Physiology ◽

10.1002/jcp.10128 ◽

2002 ◽

Vol 192 (2) ◽

pp. 182-187 ◽

Cited By ~ 119

Author(s):

Sean F. Hackett ◽

Stanley Wiegand ◽

George Yancopoulos ◽

Peter A. Campochiaro

Keyword(s):

Retinal Angiogenesis ◽

Angiopoietin 2

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Angiopoietin 2 induces astrocyte apoptosis via αvβ5-integrin signaling in diabetic retinopathy

Cell Death and Disease ◽

10.1038/cddis.2015.347 ◽

2016 ◽

Vol 7 (2) ◽

pp. e2101-e2101 ◽

Cited By ~ 24

Author(s):

J-H Yun ◽

S W Park ◽

J H Kim ◽

Y-J Park ◽

C-H Cho ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Integrin Signaling ◽

Angiopoietin 2

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Evaluation of a hospital-based integrated model of eye care for diabetic retinopathy assessment: a multimethod study

BMJ Open ◽

10.1136/bmjopen-2019-034699 ◽

2020 ◽

Vol 10 (4) ◽

pp. e034699

Author(s):

Janet C Long ◽

Brette Blakely ◽

Zeyad Mahmoud ◽

Angelica Ly ◽

Barbara Zangerl ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Hospital Staff ◽

Integrated Model ◽

Model Of Care ◽

New Model ◽

Good Communication ◽

Administrative Capacity ◽

Efficient Management ◽

Eye Health ◽

Diabetic Eye Disease

ObjectivesDiabetic eye disease is a leading cause of blindness but can be mitigated by regular eye assessment. A framework of issues, developed from the literature of barriers to eye assessment, was used to structure an examination of perceptions of a new model of care for diabetic retinopathy from the perspective of staff using the model, and health professionals referring patients to the new service.DesignMultimethod: interviews and focus groups, and a separate survey.SettingA new clinic based on an integrated model of care was established at a hospital in outer metropolitan Sydney, Australia in 2017. Funded jointly by Centre for Eye Health (CFEH) and the hospital, the clinic was equipped and staffed by optometrists who work alongside the ophthalmologists in the existing hospital eye clinic.ParticipantsFive (of seven) hospital staff working in the clinic (ophthalmologists and administrative officers) or referring to it from other departments (endocrinologists); nine optometrists from CFEH who developed or worked in the clinic; 10 community-based optometrists as potential referrers.ResultsThe new clinic was considered to have addressed known barriers to eye assessment, including access, assistance for patients unable/unwilling to organise eye checks and efficient management of human resources. The clinic optimised known drivers of this model of care: providing clear scope of practice and protocols for shared care between optometrists and ophthalmologists, good communication between referrers and eye professionals and a collegial approach promoting interprofessional trust. Remaining areas of concern were few referrals from general practitioners, fewer referrals from hospital endocrinologists than expected and issues with stretched administrative capacity. There were also perceived mismatches between the priorities of hospital management and aims of the clinic.ConclusionsThe new model was considered to have addressed many of the barriers to assessment. While there remain issues with the model, there were also unexpected benefits.

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