Diabetic retinopathy (DR), a leading cause of vision loss and blindness worldwide, is caused by retinal neurovascular unit dysfunction, and its cellular pathology involves at least nine kinds of retinal cells, including photoreceptors, horizontal and bipolar cells, amacrine cells, retinal ganglion cells, glial cells (Müller cells, astrocytes, and microglia), endothelial cells, pericytes, and retinal pigment epithelial cells. Its mechanism is complicated and involves loss of cells, inflammatory factor production, neovascularization, and BRB impairment. However, the mechanism has not been completely elucidated. Drug treatment for DR has been gradually advancing recently. Research on potential drug targets relies upon clear information on pathogenesis and effective biomarkers. Therefore, we reviewed the recent literature on the cellular pathology and the diagnostic and prognostic biomarkers of DR in terms of blood, protein, and clinical and preclinical drug therapy (including synthesized molecules and natural molecules). This review may provide a theoretical basis for further DR research.

/pdf/diabetic-retinopathy-involved-cells-biomarkers-and-5legpzy8.pdf

Diabetic retinopathy: Involved cells, biomarkers, and treatments

Deciphering the pathogenesis of retinopathy associated with carnitine palmitoyltransferase I deficiency in zebrafish model.

Diabetic retinopathy causes progressive and irreversible damage to the retina through activation of inflammatory processes, overproduction of oxidative species, and glial reactivity, leading to changes in neuronal function and finally ischemia, edema, and hemorrhages. Current treatments are invasive and mostly applied at advanced stages, stressing the need for alternatives. To this end, we tested two unconventional and potentially complementary non-invasive treatment options: Photobiomodulation, the stimulation with near-infrared light, has shown promising results in ameliorating retinal pathologies and insults in several studies but remains controversial. Boldine, on the other hand, is a potent natural antioxidant and potentially useful to prevent free radical-induced oxidative stress. To establish a baseline, we first evaluated the effects of diabetic conditions on the retina with immunofluorescence, histological, and ultrastructural analysis in two diabetes model systems, obese LepRdb/db mice and organotypic retinal explants, and then tested the potential benefits of photobiomodulation and boldine treatment in vitro on retinal explants subjected to high glucose concentrations, mimicking diabetic conditions. Our results suggest that the principal subcellular structures affected by these conditions were mitochondria in the inner segment of photoreceptors, which displayed morphological changes in both model systems. In retinal explants, lactate metabolism, assayed as an indicator of mitochondrial function, was altered, and decreased photoreceptor viability was observed, presumably as a consequence of increased oxidative-nitrosative stress. The latter was reduced by boldine treatment in vitro, while photobiomodulation improved mitochondrial metabolism but was insufficient to prevent retinal structural damage caused by high glucose. These results warrant further research into alternative and complementary treatment options for diabetic retinopathy.

Evaluation of Photobiomodulation and Boldine as Alternative Treatment Options in Two Diabetic Retinopathy Models

The retina consumes massive amounts of energy, yet its metabolism remains poorly understood. Here, we manipulated retinal energy metabolism under entirely controlled conditions and utilised 1H-NMR metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experiments resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected. Notably, rod photoreceptors relied strongly on oxidative phosphorylation, but only mildly on glycolysis. Conversely, cone photoreceptors were highly dependent on glycolysis but insensitive to electron transport chain decoupling. Moreover, photoreceptors uncouple glycolytic and Krebs-cycle metabolism via three different pathways: 1) the mini-Krebs cycle, fuelled by glutamine and branched chain amino acids, generating N-acetylaspartate; 2) the alanine-generating Cahill cycle; 3) the lactate-releasing Cori cycle. These findings forward the understanding of retinal physiology and pathology, and shed new light on neuronal energy homeostasis and the pathogenesis of neurodegenerative diseases. Graphical abstract Retinal photoreceptors employ both glucose and anaplerotic substrates as fuels. While rod photoreceptors rely strongly on oxidative phosporylation and the N-acetylaspartate producing mini Krebs-cycle, cone photoreceptors rely much more on the lacate-producing Cori-cycle and the oxidative, alanine-producing Cahill-cycle.

/pdf/retinal-energy-metabolism-photoreceptors-switch-between-cori-2508lek9.pdf

Retinal energy metabolism: Photoreceptors switch between Cori, Cahill, and mini-Krebs cycles to uncouple glycolysis from mitochondrial respiration

Hypertension and diabetes mellitus are among the most prevalent diseases affecting people from all walks of life. Medicinal herbs have garnered interest as potential agents for the prevention and treatment of diabetes mellitus and hypertension due to their multiple beneficial effects. Piper sarmentosum Roxb. (PS) is an edible medicinal plant that has been traditionally used in Asia for treating hypertension and diabetes mellitus. This review is aimed to provide comprehensive information from the literature on the effects of PS on hypertension and diabetes mellitus. A computerized database search was performed on Scopus, PubMed and Web of Science databases with the following set of keywords: Piper sarmentosum AND diabetes mellitus OR diabetic OR diabetes OR hyperglyc*emia OR blood glucose OR HbA1c OR glycated h*emoglobin OR h*emoglobin A1c OR hyperten* OR blood pressure. A total of 47 articles were screened and 14 articles published between the years 1998 until 2021 were included for data extraction, comprising of six articles on antihypertensive and eight articles on antidiabetic effects of PS. These studies consist of two in vitro studies and eleven in vivo animal studies. Meta-analysis of three studies on hypertension showed that PS versus no treatment significantly lowered the systolic blood pressure with mean difference (MD) −39.84 mmHg (95% confidence interval (CI) −45.05, −34.62; p < 0.01), diastolic blood pressure with MD −26.68 mmHg (95% CI −31.48, −21.88; p < 0.01), and mean arterial pressure with MD −30.56 mmHg (95% CI −34.49, −26.63; p < 0.01). Most of the studies revealed positive effects of PS against hypertension and diabetes mellitus, suggesting the potential of PS as a natural source of antidiabetic and antihypertensive agents.

Effects of Piper sarmentosum Roxb. on hypertension and diabetes mellitus: A systematic review and meta-analysis

The retina has the highest relative energy consumption of any tissue, depending on a steady supply of glucose from the bloodstream. Glucose uptake is mediated by specific transporters whose regulation and expression are critical for the pathogenesis of many diseases, including diabetes and diabetic retinopathy. Here, we used immunofluorescence to show that glucose transporter-2 (GLUT2) is expressed in horizontal cells of the mouse neuroretina in proximity to inner retinal capillaries. To study the function of GLUT2 in the murine retina, we used organotypic retinal explants, cultivated under entirely controlled, serum free conditions, and exposed them to streptozotocin, a cytotoxic drug transported exclusively by GLUT2. Contrary to our expectations, streptozotocin did not measurably affect horizontal cell viability, while it ablated rod and cone photoreceptors in a concentration-dependent manner. Staining for poly-ADP-ribose (PAR) indicated that the detrimental effect of streptozotocin on photoreceptors may be associated with DNA-damage. The negative effect of streptozotocin on the viability of rod photoreceptors was counteracted by co-administration of either the inhibitor of connexin-formed hemi-channels meclofenamic acid or the blocker of clathrin-mediated endocytosis dynasore. Remarkably, cone photoreceptors were not protected from streptozotocin induced degeneration by neither of the two drugs. Overall, these data suggests the existence of a GLUT2-dependent glucose transport shuttle, from horizontal cells into photoreceptor synapses. Moreover, our study points at different glucose uptake mechanisms in rod and cone photoreceptors.

Expression of glucose transporter-2 in murine retina: Evidence for glucose transport from horizontal cells to photoreceptor synapses.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Ming Yang

Author Tools

Chat about Author

Papers

Expression of glucose transporter-2 in murine retina: Evidence for glucose transport from horizontal cells to photoreceptor synapses.