Diabetic Retinopathy and NADPH Oxidase-2: A Sweet Slippery Road
Diabetic retinopathy remains the leading cause of vision loss in working-age adults. The multi-factorial nature of the disease, along with the complex structure of the retina, have hindered in elucidating the exact molecular mechanism(s) of this blinding disease. Oxidative stress appears to play a s...
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| description | Diabetic retinopathy remains the leading cause of vision loss in working-age adults. The multi-factorial nature of the disease, along with the complex structure of the retina, have hindered in elucidating the exact molecular mechanism(s) of this blinding disease. Oxidative stress appears to play a significant role in its development and experimental models have shown that an increase in cytosolic Reacttive Oxygen Speies (ROS) due to the activation of NADPH oxidase 2 (Nox2), is an early event, which damages the mitochondria, accelerating loss of capillary cells. One of the integral proteins in the assembly of Nox2 holoenzyme, Rac1, is also activated in diabetes, and due to epigenetic modifications its gene transcripts are upregulated. Moreover, addition of hyperlipidemia in a hyperglycemic milieu (type 2 diabetes) further exacerbates Rac1-Nox2-ROS activation, and with time, this accelerates and worsens the mitochondrial damage, ultimately leading to the accelerated capillary cell loss and the development of diabetic retinopathy. Nox2, a multicomponent enzyme, is a good candidate to target for therapeutic interventions, and the inhibitors of Nox2 and Rac1 (and its regulators) are in experimental or clinical trials for other diseases; their possible use to prevent/halt retinopathy will be a welcoming sign for diabetic patients. |
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The multi-factorial nature of the disease, along with the complex structure of the retina, have hindered in elucidating the exact molecular mechanism(s) of this blinding disease. Oxidative stress appears to play a significant role in its development and experimental models have shown that an increase in cytosolic Reacttive Oxygen Speies (ROS) due to the activation of NADPH oxidase 2 (Nox2), is an early event, which damages the mitochondria, accelerating loss of capillary cells. One of the integral proteins in the assembly of Nox2 holoenzyme, Rac1, is also activated in diabetes, and due to epigenetic modifications its gene transcripts are upregulated. Moreover, addition of hyperlipidemia in a hyperglycemic milieu (type 2 diabetes) further exacerbates Rac1-Nox2-ROS activation, and with time, this accelerates and worsens the mitochondrial damage, ultimately leading to the accelerated capillary cell loss and the development of diabetic retinopathy. Nox2, a multicomponent enzyme, is a good candidate to target for therapeutic interventions, and the inhibitors of Nox2 and Rac1 (and its regulators) are in experimental or clinical trials for other diseases; their possible use to prevent/halt retinopathy will be a welcoming sign for diabetic patients.</description><identifier>ISSN: 2076-3921</identifier><identifier>EISSN: 2076-3921</identifier><identifier>DOI: 10.3390/antiox10050783</identifier><identifier>PMID: 34063353</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Apoptosis ; Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Clinical trials ; CYBB protein ; Cytochrome ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetic retinopathy ; Enzymes ; Epigenetics ; Food Science & Technology ; Free radicals ; Glucose ; Hyperglycemia ; Hyperlipidemia ; Kinases ; Life Sciences & Biomedicine ; Metabolism ; Mitochondria ; NAD(P)H oxidase ; NADPH oxidase ; Oxidative stress ; Pathogenesis ; Patients ; Pharmacology & Pharmacy ; Proteins ; Rac1 protein ; Reactive oxygen species ; Retina ; Retinopathy ; Review ; Science & Technology ; Therapeutic applications ; Vascular endothelial growth factor</subject><ispartof>Antioxidants, 2021-05, Vol.10 (5), p.783, Article 783</ispartof><rights>2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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The multi-factorial nature of the disease, along with the complex structure of the retina, have hindered in elucidating the exact molecular mechanism(s) of this blinding disease. Oxidative stress appears to play a significant role in its development and experimental models have shown that an increase in cytosolic Reacttive Oxygen Speies (ROS) due to the activation of NADPH oxidase 2 (Nox2), is an early event, which damages the mitochondria, accelerating loss of capillary cells. One of the integral proteins in the assembly of Nox2 holoenzyme, Rac1, is also activated in diabetes, and due to epigenetic modifications its gene transcripts are upregulated. Moreover, addition of hyperlipidemia in a hyperglycemic milieu (type 2 diabetes) further exacerbates Rac1-Nox2-ROS activation, and with time, this accelerates and worsens the mitochondrial damage, ultimately leading to the accelerated capillary cell loss and the development of diabetic retinopathy. Nox2, a multicomponent enzyme, is a good candidate to target for therapeutic interventions, and the inhibitors of Nox2 and Rac1 (and its regulators) are in experimental or clinical trials for other diseases; their possible use to prevent/halt retinopathy will be a welcoming sign for diabetic patients.</description><subject>Apoptosis</subject><subject>Biochemistry & Molecular Biology</subject><subject>Chemistry, Medicinal</subject><subject>Clinical trials</subject><subject>CYBB protein</subject><subject>Cytochrome</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetic retinopathy</subject><subject>Enzymes</subject><subject>Epigenetics</subject><subject>Food Science & Technology</subject><subject>Free radicals</subject><subject>Glucose</subject><subject>Hyperglycemia</subject><subject>Hyperlipidemia</subject><subject>Kinases</subject><subject>Life Sciences & Biomedicine</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>NAD(P)H oxidase</subject><subject>NADPH oxidase</subject><subject>Oxidative stress</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Pharmacology & Pharmacy</subject><subject>Proteins</subject><subject>Rac1 protein</subject><subject>Reactive oxygen species</subject><subject>Retina</subject><subject>Retinopathy</subject><subject>Review</subject><subject>Science & Technology</subject><subject>Therapeutic applications</subject><subject>Vascular endothelial growth 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A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-13c74f1118b5be4d5f0c6a32da25cc02e063d35f051d721ab2ff861500a20c5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis</topic><topic>Biochemistry & Molecular Biology</topic><topic>Chemistry, Medicinal</topic><topic>Clinical trials</topic><topic>CYBB protein</topic><topic>Cytochrome</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetic retinopathy</topic><topic>Enzymes</topic><topic>Epigenetics</topic><topic>Food Science & Technology</topic><topic>Free radicals</topic><topic>Glucose</topic><topic>Hyperglycemia</topic><topic>Hyperlipidemia</topic><topic>Kinases</topic><topic>Life Sciences & Biomedicine</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>NAD(P)H oxidase</topic><topic>NADPH oxidase</topic><topic>Oxidative stress</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Pharmacology & Pharmacy</topic><topic>Proteins</topic><topic>Rac1 protein</topic><topic>Reactive oxygen species</topic><topic>Retina</topic><topic>Retinopathy</topic><topic>Review</topic><topic>Science & Technology</topic><topic>Therapeutic applications</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kowluru, Renu A.</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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The multi-factorial nature of the disease, along with the complex structure of the retina, have hindered in elucidating the exact molecular mechanism(s) of this blinding disease. Oxidative stress appears to play a significant role in its development and experimental models have shown that an increase in cytosolic Reacttive Oxygen Speies (ROS) due to the activation of NADPH oxidase 2 (Nox2), is an early event, which damages the mitochondria, accelerating loss of capillary cells. One of the integral proteins in the assembly of Nox2 holoenzyme, Rac1, is also activated in diabetes, and due to epigenetic modifications its gene transcripts are upregulated. Moreover, addition of hyperlipidemia in a hyperglycemic milieu (type 2 diabetes) further exacerbates Rac1-Nox2-ROS activation, and with time, this accelerates and worsens the mitochondrial damage, ultimately leading to the accelerated capillary cell loss and the development of diabetic retinopathy. Nox2, a multicomponent enzyme, is a good candidate to target for therapeutic interventions, and the inhibitors of Nox2 and Rac1 (and its regulators) are in experimental or clinical trials for other diseases; their possible use to prevent/halt retinopathy will be a welcoming sign for diabetic patients.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>34063353</pmid><doi>10.3390/antiox10050783</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-3309-4942</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Biochemistry & Molecular Biology Chemistry, Medicinal Clinical trials CYBB protein Cytochrome Diabetes Diabetes mellitus (non-insulin dependent) Diabetic retinopathy Enzymes Epigenetics Food Science & Technology Free radicals Glucose Hyperglycemia Hyperlipidemia Kinases Life Sciences & Biomedicine Metabolism Mitochondria NAD(P)H oxidase NADPH oxidase Oxidative stress Pathogenesis Patients Pharmacology & Pharmacy Proteins Rac1 protein Reactive oxygen species Retina Retinopathy Review Science & Technology Therapeutic applications Vascular endothelial growth factor |
| title | Diabetic Retinopathy and NADPH Oxidase-2: A Sweet Slippery Road |
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