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1.
The Role of HIF1α-PFKFB3 Pathway in Diabetic Retinopathy.
Min, J, Zeng, T, Roux, M, Lazar, D, Chen, L, Tudzarova, S
The Journal of clinical endocrinology and metabolism. 2021;(9):2505-2519
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Abstract
Diabetic retinopathy (DR) is the leading cause of blindness for adults in developed countries. Both microvasculopathy and neurodegeneration are implicated in mechanisms of DR development, with neuronal impairment preceding microvascular abnormalities, which is often underappreciated in the clinic. Most current therapeutic strategies, including anti-vascular endothelial growth factor (anti-VEGF)-antibodies, aim at treating the advanced stages (diabetic macular edema and proliferative diabetic retinopathy) and fail to target the neuronal deterioration. Hence, new therapeutic approach(es) intended to address both vascular and neuronal impairment are urgently needed. The hypoxia-inducible factor 1α (HIF1α)-6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) pathway is critically implicated in the islet pathology of diabetes. Recent evidence highlighted the pathway relevance for pathologic angiogenesis and neurodegeneration, two key aspects in DR. PFKFB3 is key to the sprouting angiogenesis, along with VEGF, by determining the endothelial tip-cell competition. Also, PFKFB3-driven glycolysis compromises the antioxidative capacity of neurons leading to neuronal loss and reactive gliosis. Therefore, the HIF1α-PFKFB3 signaling pathway is unique as being a pervasive pathological component across multiple cell types in the retina in the early as well as late stages of DR. A metabolic point-of-intervention based on HIF1α-PFKFB3 targeting thus deserves further consideration in DR.
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Pyroptosis in the Retinal Neurovascular Unit: New Insights Into Diabetic Retinopathy.
Meng, C, Gu, C, He, S, Su, T, Lhamo, T, Draga, D, Qiu, Q
Frontiers in immunology. 2021;:763092
Abstract
Diabetic retinopathy (DR) is prevalent among people with long-term diabetes mellitus (DM) and remains the leading cause of visual impairment in working-aged people. DR is related to chronic low-level inflammatory reactions. Pyroptosis is an emerging type of inflammatory cell death mediated by gasdermin D (GSDMD), NOD-like receptors and inflammatory caspases that promote interleukin-1β (IL-1β) and IL-18 release. In addition, the retinal neurovascular unit (NVU) is the functional basis of the retina. Recent studies have shown that pyroptosis may participate in the destruction of retinal NVU cells in simulated hyperglycemic DR environments. In this review, we will clarify the importance of pyroptosis in the retinal NVU during the development of DR.
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Screening recommendations for diabetics.
Robin, A, Giovingo, M
Disease-a-month : DM. 2021;(5):101116
Abstract
Diabetes is one of the leading causes of morbidity and mortality in the United States. Patients with diabetes are at risk for multiple ophthalmologic complications including, but not limited to, cataracts, glaucoma, and retinopathy. Eye-exams are an important screening tool for patients with diabetes in order to prevent the more severe and vision-threatening sequela of disease. Early detection and treatment of diabetic retinopathy can result in a significant decrease in vision-loss. However, recent estimates demonstrate that few diabetic patients meet the recommended screening guidelines. Appropriate referral and follow-up is important for monitoring the ophthalmologic conditions associated with diabetes. Our purpose is to review current recommendations for ophthalmic screening for patients with diabetes in a clear and concise manor for primary care physicians.
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Correlation of OCT Angiography Vessel Densities and the Early Treatment Diabetic Retinopathy Study Grading Scale.
Mehta, NS, Lee, JG, Gupta, L, Zhou, DB, Andrade Romo, JS, Castanos, MV, Jansen, M, Ping Chui, TY, Rosen, RB
Ophthalmology. Retina. 2021;(7):714-715
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Clinical Role of Smartphone Fundus Imaging in Diabetic Retinopathy and Other Neuro-retinal Diseases.
Pujari, A, Saluja, G, Agarwal, D, Sinha, A, P R, A, Kumar, A, Sharma, N
Current eye research. 2021;(11):1605-1613
Abstract
Purpose: In today's life, many electronic gadgets have the potential to become invaluable health care devices in future. The gadgets in this category include smartphones, smartwatches, and others. Till now, smartphone role has been highlighted on many occasions in different areas, and they continue to possess immense role in clinical documentation, clinical consultation, and digitalization of ocular care. In last one decade, many treatable conditions including diabetic retinopathy, glaucoma, and other pediatric retinal diseases are being imaged using smartphones.Methods: To comprehend this cumulative knowledge, a detailed medical literature search was conducted on PubMed/Medline, Scopus, and Web of Science till February 2021.Results: The included literature revealed a definitive progress in posterior segment imaging. From simple torch light with smartphone examination to present day compact handy devices with artificial intelligence integrated software's have changed the very perspectives of ocular imaging in ophthalmology. The consistently reproducible results, constantly improving imaging techniques, and most importantly their affordable costs have renegotiated their role as effective screening devices in ophthalmology. Moreover, the obtained field of view, ocular safety, and their key utility in non-ophthalmic specialties are also growing.Conclusions: To conclude, smartphone imaging can now be considered as a quick, cost-effective, and digitalized tool for posterior segment screenings, however, their definite role in routine ophthalmic clinics is yet to be established.
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Imaging the eye and its relevance to diabetes care.
Quinn, N, Jenkins, A, Ryan, C, Januszewski, A, Peto, T, Brazionis, L
Journal of diabetes investigation. 2021;(6):897-908
Abstract
Diabetes is a major cause of vision loss globally, yet this devastating complication is largely preventable. Early detection and treatment of diabetic retinopathy necessitates screening. Ocular imaging is widely used clinically, both for the screening and management of diabetic retinopathy. Common eye conditions, such as glaucoma, cataracts and retinal vessel thrombosis, and signs of systemic conditions, such as hypertension, are frequently revealed. As well as imaging by a skilled clinician during an eye examination, non-ophthalmic clinicians, such as general practitioners, endocrinologists, nurses and trained health workers, can also can carry out diabetic eye screening. This process usually comprises local imaging with remote grading, mostly human grading. However, grading incorporating artificial intelligence is emerging. In a clinical research context, retinal vasculature analyses using semi-automated software in many populations have identified associations between retinal vessel geometry, such as vessel caliber, and the risk of diabetic retinopathy and other chronic complications of type 1 and type 2 diabetes. Similarly, evaluation of corneal nerves by corneal confocal microscopy is revealing diabetes-related abnormalities, and associations with and predictive power for other chronic diabetes complications. As yet, the value of retinal vessel geometry and corneal confocal microscopy measures at an individual level is uncertain. In this article, targeting non-ocular clinicians and researchers, we review existent and emerging ocular imaging and grading tools, including artificial intelligence, and their associations between ocular imaging findings and diabetes and its chronic complications.
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The Impact of Bariatric Surgery on Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
Yu, CW, Park, LJ, Pinto, A, Ma, ON, Lee, Y, Gupta, R, Chaudhary, V, Doumouras, AG, Hong, D
American journal of ophthalmology. 2021;:117-127
Abstract
OBJECTIVE While bariatric surgery induces remission of type 2 diabetes mellitus and reduces other microvascular complications, its impact on diabetic retinopathy (DR) is unclear. Some trials suggest early worsening of DR postsurgery because of rapid improvements in hyperglycemia. This meta-analysis sought to estimate the impact of bariatric surgery on DR for obese patients compared with medical treatment. DESIGN Systematic review and meta-analysis. METHODS The Medline, Embase, and PubMed Central databases were searched to March 2020. Primary studies comparing DR in patients undergoing bariatric surgery with those undergoing medical management were included. Results were meta-analyzed using a random-effects model. Primary outcomes included prevalence of all DR and sight-threatening DR after surgery. Secondary outcomes included worsening of DR within and beyond 12 months. RESULTS Overall, 14 studies comprised of 110,300 surgical patients and 252,289 control subjects were included. Surgical patients had a statistically significantly lower postoperative prevalence of all DR (relative risk [RR] 0.17 [95% confidence interval {CI} 0.13-0.22]) and sight-threatening DR (RR 0.47 [95% CI 0.27-0.82]). Early worsening of DR and progression to sight-threatening DR had occurred more often in those with more severe DR initially. However, beyond 12 months, bariatric surgery resulted in significantly fewer patients with worsened DR (RR 0.29 [95% CI 0.16-0.54]). The overall risk of bias was low; estimates of relative effects had low to moderate certainty of evidence. CONCLUSION While bariatric surgery was associated with fewer cases of all and sight-threatening DR, early worsening was more severe in patients with existing sight-threatening DR. These findings argue for frequent monitoring during the first postoperative year.
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13. Tractional retinal detachments.
Solinski, MA, Mylvaganam, H, Adenwalla, M, Ghadiali, Q
Disease-a-month : DM. 2021;(5):101142
Abstract
Tractional retinal detachments (TRD) occur as a consequence of various retinal pathologies but is most commonly associated with proliferative diabetic retinopathy (PDR). Monitoring for diabetic eye disease and early identification of TRD are crucial for preventing vision loss.
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Diabetic Retinopathy and Vascular Endothelial Growth Factor Gene Insertion/Deletion Polymorphism.
Khan, SZ, Ajmal, N, Shaikh, R
Canadian journal of diabetes. 2020;(3):287-291
Abstract
Diabetic retinopathy (DR) is a microvascular complication of the retina of the eye and represents a major cause of blindness worldwide. It is a complex disorder characterized by both genetic and environmental factors. The vascular endothelial growth factor (VEGF) gene is among the main candidate genes for DR, as it is also involved in several other diseases, such as microvascular complications of diabetes mellitus and cancer. The VEGF gene is extremely polymorphic. The 18-bp fragment (insertion/deletion) polymorphism at the -2549 position of the promoter region of the VEGF gene is of great importance. In this review, we highlight the DR and VEGF gene (insertion/deletion) polymorphism. In addition, we assess this association in various DR populations and in other microvascular complications, such as diabetic nephropathy, diabetic peripheral neuropathy and cancer.
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10.
αB-crystallin as a promising target in pathological conditions - A review.
Maksimiuk, M, Sobiborowicz, A, Tuzimek, A, Deptała, A, Czerw, A, Badowska-Kozakiewicz, AM
Annals of agricultural and environmental medicine : AAEM. 2020;(3):326-334
Abstract
INTRODUCTION AND OBJECTIVE αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. STATE OF KNOWLEDGE α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. CONCLUSIONS Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.