Review
Pharmacology & Pharmacy
Rafael Simo, Olga Simo-Servat, Patricia Bogdanov, Cristina Hernandez
Summary: The concept of diabetic retinopathy has evolved to consider neurovascular unit impairment as a main target for therapeutic strategies. While neurodegeneration may not always be the primary event in the progression of the disease, phenotyping to identify patients who could benefit from neuroprotective treatments is recommended. Recent research has tested numerous neuroprotective treatments, including drugs with dual activity, aiming to address the complex nature of diabetic retinopathy.
Review
Ophthalmology
Shen Nian, Amy C. Y. Lo, Yajing Mi, Kai Ren, Di Yang
Summary: Diabetic retinopathy is a complex neurovascular disease that affects both vascular structure and neural tissue of the retina. Deterioration of neural retina may precede microvascular abnormalities, leading to changes in the microvasculature.
Article
Plant Sciences
Lixia Chen, Yilan Zhen, Xuncui Wang, Jingji Wang, Guoqi Zhu
Summary: This review discusses the potential of herbal medicines in improving cognitive impairment from the perspective of the neurovascular glial unit (NVGU). The NVGU consists of various cells, and damage to these cells can lead to cognitive impairment by affecting the blood-brain barrier and cerebral blood flow. Herbal medicines have shown potential in improving blood-brain barrier function and increasing cerebral blood flow to prevent cognitive impairment.
Review
Biochemistry & Molecular Biology
Toshiyuki Oshitari
Summary: Diabetic retinopathy (DR) is a common complication of diabetes and a prominent cause of blindness globally. Recently, DR has been defined as a neurovascular disease that impairs the retinal neurovascular function in individuals with diabetes. Neurovascular cell death is the primary cause of this impairment, and protecting neurovascular cells offers a potential therapy for preventing DR progression. Various cell death pathways, including apoptosis, necroptosis, ferroptosis, and pyroptosis, are associated with neurovascular cell death in DR, and targeting these regulated cell death mechanisms may serve as therapies to ameliorate DR pathogenesis. This review focuses on these cell death mechanisms and presents potential therapies that protect against neurovascular cell death in the treatment of DR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Chunren Meng, Chufeng Gu, Shuai He, Tong Su, Thashi Lhamo, Deji Draga, Qinghua Qiu
Summary: Pyroptosis is an emerging type of inflammatory cell death that may play a crucial role in the development of diabetic retinopathy, potentially contributing to the destruction of retinal neurovascular unit cells in hyperglycemic conditions.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Chiara Simone Middel, Hans-Peter Hammes, Jens Kroll
Summary: Zebrafish have emerged as a valuable model organism for studying diabetic retinopathy, providing insights into the role of different cell types in the disease and allowing observation of hyperglycemia-induced retinal angiogenesis. Utilizing zebrafish for research on diabetic retinopathy has the potential to advance the field further and propose new investigations.
Article
Cell Biology
Tian Yuan, Lijie Dong, Elizabeth A. Pearsall, Kelu Zhou, Rui Cheng, Jian-Xing Ma
Summary: PPAR alpha plays a critical role in pathological microgliosis, neurodegeneration, and vascular damage in diabetic retinopathy; the study reveals the underlying molecular mechanisms of microgliosis, and suggests microglial PPAR alpha as a potential therapeutic target.
Review
Clinical Neurology
Golnoush Mirzahosseini, Justin Mark Adam, Sanaz Nasoohi, Azza B. El-Remessy, Tauheed Ishrat
Summary: The neurovascular unit is the functional unit of the brain and retina, and neurotrophins play an important role in neuronal differentiation, survival, and neurite outgrowth. Recent studies have shown that neurovascular dysfunction in the neurovascular unit is regulated by neurotrophins and their receptors.
Article
Ophthalmology
Rehna Rasheed, Gopal S. Pillai, Harish Kumar, Adish Thayyil Shajan, Natasha Radhakrishnan, Greeshma C. Ravindran
Summary: This study identified a significant association between DR and DPN, with risk factors including duration of DM, HbA1c levels, and serum creatinine. Additionally, significant thinning of GCIPL was observed in DR patients, highlighting the importance of a multidisciplinary approach in managing diabetes and its complications.
INDIAN JOURNAL OF OPHTHALMOLOGY
(2021)
Review
Endocrinology & Metabolism
Xiongyi Yang, Zexin Huang, Mei Xu, Yanxia Chen, Mingzhe Cao, Guoguo Yi, Min Fu
Summary: Diabetic retinopathy (DR) is a common retinal disorder that causes vision impairment in the productive age group. Autophagy, a critical intracellular mechanism, plays a significant role in DR by maintaining cellular homeostasis and regulating cell fate. The retinal neurovascular unit (NVU), as the retina's functional unit, is dependent on autophagy for normal structure and function.
JOURNAL OF DIABETES
(2023)
Article
Neurosciences
Maria H. Madeira, Ines P. Marques, Sonia Ferreira, Diana Tavares, Torcato Santos, Ana Rita Santos, Joao Figueira, Conceicao Lobo, Jose Cunha-Vaz
Summary: Diabetic retinopathy is not only a microvascular disease, but also involves neurodegeneration, with different phenotypes identified based on the characteristics of neurodegeneration. Understanding these phenotypes may offer insights for improved treatment and management of diabetic individuals with retinopathy.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Shengdan Pu, Yuxin Xu, Xin Li, Ziwei Yu, Yitong Zhang, Xuewei Tong, Yongyan Shan, Xinyuan Gao
Summary: Diabetic retinopathy (DR) is a neurovascular disease whose exact mechanism is still unclear. Long noncoding RNAs (lncRNAs) play a key regulatory role in various cellular components and show promise for targeted treatment of DR.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Liyang Ji, Hong Tian, Keith A. Webster, Wei Li
Summary: Diabetic retinopathy is the leading cause of vision loss in working adults in developed countries, now recognized as a neurovascular disorder. Disturbance of the neurovascular unit can lead to vision-threatening clinical manifestations. While VEGF inhibitors are widely used to treat DR, their limited efficacy suggests the involvement of other signaling molecules in the pathogenesis of the disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Medicine, General & Internal
Edoardo Midena, Tommaso Torresin, Evelyn Longhin, Giulia Midena, Elisabetta Pilotto, Luisa Frizziero
Summary: The study found early microvascular changes and alterations in oscillatory potentials in the retina of diabetic patients, regardless of the presence of diabetic retinopathy. The reduced oscillatory potentials suggest a precocious involvement of amacrine cells in diabetic eyes, and the correlation with vascular parameters emphasizes the importance of the crosstalk between retinal cells and blood vessels in the pathophysiology of this chronic disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Tam Thuy Lu Vo, Dain Shin, Eunyoung Ha, Ji Hae Seo
Summary: This review examines the harmful effects of drug abuse on the blood-brain barrier (BBB), with a focus on the mechanisms through which it damages the neurovascular unit (NVU). Understanding the relationships between drug abuse, BBB integrity, and NVU function may lead to the discovery of new therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Karis Little, Maria Llorian-Salvador, Sarah Scullion, Cristina Hernandez, Olga Simo-Servat, Angel del Marco, Esmeralda Bosma, Maria Vargas-Soria, Maria Jose Carranza-Naval, Tine Van Bergen, Silvia Galbiati, Ilaria Vigano, Clara Alice Musi, Reiner Schlingemann, Jean Feyen, Tiziana Borsello, Gianpaolo Zerbini, Ingeborg Klaassen, Monica Garcia-Alloza, Rafael Simo, Alan W. Stitt
Summary: Type 2 diabetes is associated with complications like diabetic retinopathy and cognitive decline, with chronic hyperglycemia and insulin resistance playing crucial roles. Understanding these common pathological mechanisms may help in identifying T2D patients at risk of cognitive decline.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Chemistry, Multidisciplinary
Ruben G. Barriada, Olga Simo-Servat, Alejandra Planas, Cristina Hernandez, Rafael Simo, David Masip
Summary: This study explores the use of deep learning models for predicting cardiovascular risk based on retina fundus imaging. The results show that combining image analysis with clinical data can provide a better assessment of cardiovascular disease risk.
APPLIED SCIENCES-BASEL
(2022)
Article
Biochemistry & Molecular Biology
Kevin Harkin, Josy Augustine, Alan W. Stitt, Heping Xu, Mei Chen
Summary: This study found that Wedelolactone (WD) can protect against N-methyl-N-nitrosourea (NMU) induced retinal neurodegeneration by suppressing the inflammasome-related pathway. The results showed that WD can attenuate the impairment of retinal function and structure caused by NMU and reduce the expression of inflammasome-related genes.
Review
Cell & Tissue Engineering
Judith Lechner, Reinhold J. Medina, Noemi Lois, Alan W. Stitt
Summary: Diabetic retinopathy, a complication of diabetes, is a leading cause of vision loss in working age adults. The loss of integrity of the retinal neurovascular unit is central to the disease pathogenesis. Current treatment options are limited to late-stages of the disease, and new treatments are needed to target early stages and prevent vision loss.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Pediatrics
Jessica A. Omand, Xuedi Li, Charles D. G. Keown-Stoneman, Cornelia M. Borkhoff, Eric Duku, Gerald Lebovic, Jonathon L. Maguire, Muhammad M. Mamdani, Patricia C. Parkin, Caroline Reid-Westoby, Janis Randall Simpson, Mark S. Tremblay, Magdalena Janus, Catherine S. Birken
Summary: This study investigates the association between body weight in early childhood and school readiness in young children. Being classified as overweight or with obesity was found to be associated with poor school readiness in year 2 of kindergarten. Early interventions to promote healthy growth before school entry may help promote development and school readiness in young children.
Article
Medicine, General & Internal
Courtney A. South, Charles D. G. Keown-Stoneman, Catherine S. Birken, Vasanti S. Malik, Stanley H. Zlotkin, Jonathon L. Maguire
Summary: This study examined the association between underweight in the first 2 years of life and growth in later childhood, and found that underweight in the first 2 years is associated with lower zBMI and HAZ in later childhood.
Article
Biochemistry & Molecular Biology
Hugo Ramos, Patricia Bogdanov, Rafael Simo, Anna Deas-Just, Cristina Hernandez
Summary: Synaptic dysfunction and neuronal damage are closely associated with diabetic retinopathy (DR). This study explored the effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on retinal expression patterns in an experimental model of DR. Transcriptome analysis revealed that sitagliptin eye drops significantly affected retinal expression patterns, with neurotransmission being the most enriched biological process. The study suggests that topical administration of sitagliptin improves abnormalities in presynaptic and postsynaptic signal transmission during DR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Jose Raul Herance, Andreea Ciudin, Ruben Lamas-Domingo, Carolina Aparicio-Gomez, Cristina Hernandez, Rafael Simo, Martina Palomino-Schatzlein
Summary: The prevalence of diabetes type 1 (T1D) is increasing worldwide. This study aimed to find new biomarkers of T1D in red blood cells (RBCs), which have not been explored before. The metabolomic and lipidomic profiles of RBCs from T1D patients and healthy controls were analyzed using NMR spectroscopy. Significant changes were observed in amino acids, organic acids, creatine, phosphocreatine, lipid length, and choline derivatives. These changes indicate alterations in glycolysis, BCAA metabolism, and phospholipid metabolism. The study concluded that the metabolic and lipidomic profile of RBCs can be used as biomarker candidates for the earlier diagnosis and monitoring of T1D patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Hugo Ramos, Cristina Hernandez, Rafael Simo, Olga Simo-Servat
Summary: The etiology of diabetic retinopathy (DR) involves multiple factors and affects the retinal neurovascular unit (NVU). DR has a chronic low-grade inflammatory component, and understanding its mechanisms allows the development of new therapeutic strategies. This review article summarizes the latest research on the role of inflammation in DR and discusses the efficacy of current anti-inflammatory treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Queralt Martin-Saladich, Rafael Simo, Santiago Aguade-Bruix, Olga Simo-Servat, Carolina Aparicio-Gomez, Cristina Hernandez, Clara Ramirez-Serra, Maria Nazarena Pizzi, Albert Roque, Miguel A. Gonzalez A. Ballester, Jose Raul Herance
Summary: In this study, the myocardial dynamics in insulin-sensitive (mIS) and insulin-resistant (mIR) type 2 diabetes (T2D) patients were investigated for the first time. The results suggest that there are different risk indicators for mIS and highly calcified subjects, and personalized approaches to assess T2D may lead to more efficient treatments and risk-prevention strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Nuria Alcubierre, Minerva Granado-Casas, Patricia Bogdanov, Cristina Hernandez, Hugo Ramos, Esmeralda Castelblanco, Jordi Real, Esther Rubinat-Arnaldo, Alicia Traveset, Marta Hernandez, Carmen Jurjo, Jesus Vioque, Eva Maria Navarrete-Munoz, Rafael Simo, Didac Mauricio
Summary: The study evaluated the potential benefits of caffeine intake in preventing the development of diabetic retinopathy (DR) in patients with type 2 diabetes (T2D). The cross-sectional study showed a protective effect of moderate and high caffeine intake on DR. However, the experimental model did not demonstrate any improvement in reactive gliosis or retinal vascular permeability with caffeine administration.
Article
Cell Biology
Josy Augustine, Sofia Pavlou, Kevin Harkin, Alan W. Stitt, Heping Xu, Mei Chen
Summary: Diabetic retinopathy (DR) leads to visual impairment and blindness due to dysfunction and inflammation of Mu'' ller cells. Interleukin-33 (IL-33) plays a crucial immunomodulatory role in DR, and its absence promotes inflammation, neurodegeneration, and decreased neurotrophin secretion.
DISEASE MODELS & MECHANISMS
(2023)
Article
Multidisciplinary Sciences
Sara G. Romeo, Ilaria Secco, Edoardo Schneider, Christina M. Reumiller, Celio X. C. Santos, Anna Zoccarato, Vishal Musale, Aman Pooni, Xiaoke Yin, Konstantinos Theofilatos, Silvia Cellone Trevelin, Lingfang Zeng, Giovanni E. Mann, Varun Pathak, Kevin Harkin, Alan W. Stitt, Reinhold J. Medina, Andriana Margariti, Manuel Mayr, Ajay M. Shah, Mauro Giacca, Anna Zampetaki
Summary: The microvasculature is critical for the delivery of oxygen and metabolites throughout tissues. In this study, human blood vessel organoids (BVOs) were used to show that CTGF is a critical paracrine regulator of microvascular integrity that can restore pericyte coverage and vessel structure.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Angel Ortiz-Zuniga, Olga Simo-Servat, Judit Amigo, Monica Sanchez, Carla Morer, Josep Franch-Nadal, Regina Mayor, Tim Snel, Rafael Simo, Cristina Hernandez
Summary: This study evaluated the efficacy of self-management of insulin titration based on information received by the Short Message Service (SMS). The results showed that SMS-guided titration improved glycemic control and significantly improved psychological aspects related to insulin treatment.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Betina Biagetti, Irene Valenzuela, Ariadna Campos-Martorell, Berta Campos, Sara Hernandez, Marina Giralt, Noelia Diaz-Troyano, Emilio Iniesta-Serrano, Diego Yeste, Rafael Simo
Summary: This report describes a case of short stature in an adult patient with homozygous variants in the ADAMTS17 and GHS-R genes. The patient exhibited severe short stature, small hands and feet, and eye disturbances. Genetic testing revealed compound homozygosity for ADAMTS17, responsible for Weill-Marchesani-like syndrome, as well as homozygous variants in the GHS-R gene. Dynamic stimulation tests showed a normal GH response to insulin tolerance test but a flattened response to macimorelin stimulus. The findings provide insights into the clinical spectrum, associated co-morbidities, implications in dynamic tests, genetic counseling, and treatment options for both the index case and her relatives.