ArticleProceedings of the National Academy of Sciences of the United States of America2017
Protective effects of agonists of growth hormone-releasing hormone (GHRH) in early experimental diabetic retinopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Growth hormone-releasing hormone attenuates amyloid deposition and neuroinflammation in Alzheimer's disease models.Cell death & disease · 2026Article
- Role of Growth Hormone (GH) and Other Somatotropic Axis Elements in Retinal Neuroprotection.Current issues in molecular biology · 2026Review
- Inhibiting the uPAR/FPR1 interactions reduces blood-retinal barrier breakdown and improves retinal function in a rat model of diabetes.Frontiers in neuroscience · 2026Article
- Therapeutic potential of growth hormone-releasing hormone analogues in cardiovascular and cerebrovascular diseases: mechanisms and preclinical evidence.Frontiers in pharmacology · 2026Review
- Growth hormone-releasing hormone in retinal disorders and uveitis: an updated review.International journal of ophthalmology · 2026Review
- GHRH in diabetes and metabolism.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone receptor (GHRH-R) and its signaling.Reviews in endocrine & metabolic disorders · 2025Review
- Effects of GHRH and its analogues on the Vascular System.Reviews in endocrine & metabolic disorders · 2025Review
- GHRH and reproductive systems: Mechanisms, functions, and clinical implications.Reviews in endocrine & metabolic disorders · 2025Review
- Oral 8-aminoguanine against age-related retinal degeneration.Communications biology · 2025Article
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- Renoprotective effects of GHRH agonist MR409 is associated with reduced oxidative stress and ferroptosis in diabetic mice.Frontiers in pharmacology · 2025Article
- GHRH agonist MR-409 protects β-cells from streptozotocin-induced diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.Nature communications · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Agonist of growth hormone-releasing hormone improves the disease features of spinal muscular atrophy mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Growth hormone-releasing hormone agonist attenuates vascular calcification in diabetic db/db mice.Frontiers in cardiovascular medicine · 2023Article
- Growth hormone-releasing hormone receptor signaling in experimental ocular inflammation and neuroprotection.Neural regeneration research · 2022Review
- Retinal Gene Expression of Selective Genes and Histological Stages of Embryonic and Post-Hatch Chickens (Genes · 2022Article
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11 authors at 3 institutions in 1 country.
Funding
Abstract
The potential therapeutic effects of agonistic analogs of growth hormone-releasing hormone (GHRH) and their mechanism of action were investigated in diabetic retinopathy (DR). Streptozotocin-induced diabetic rats (STZ-rats) were treated with 15 μg/kg GHRH agonist, MR-409, or GHRH antagonist, MIA-602. At the end of treatment, morphological and biochemical analyses assessed the effects of these compounds on retinal neurovascular injury induced by hyperglycemia. The expression levels of GHRH and its receptor (GHRH-R) measured by qPCR and Western blotting were significantly down-regulated in retinas of STZ-rats and in human diabetic retinas (postmortem) compared with their respective controls. Treatment of STZ-rats with the GHRH agonist, MR-409, prevented retinal morphological alteration induced by hyperglycemia, particularly preserving survival of retinal ganglion cells. The reverse, using the GHRH antagonist, MIA-602, resulted in worsening of retinal morphology and a significant alteration of the outer retinal layer. Explaining these results, we have found that MR-409 exerted antioxidant and anti-inflammatory effects in retinas of the treated rats, as shown by up-regulation of NRF-2-dependent gene expression and down-regulation of proinflammatory cytokines and adhesion molecules. MR-409 also significantly down-regulated the expression of vascular endothelial growth factor while increasing that of pigment epithelium-derived factor in diabetic retinas. These effects correlated with decreased vascular permeability. In summary, our findings suggest a neurovascular protective effect of GHRH analogs during the early stage of diabetic retinopathy through their antioxidant and anti-inflammatory properties.
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