Protective effects of agonists of growth hormone-releasing hormone (GHRH) in early experimental diabetic retinopathy.
Thounaojam. Menaka C MC; Powell. Folami L FL; Patel. Sagar S; Gutsaeva. Diana R DR; Tawfik. Amany A; Smith. Sylvia B SB; Nussbaum. Julian J; Block. Norman L NL; Martin. Pamela M PM; Schally. Andrew V AV; Bartoli. Manuela M
Key Findings
- GHRH and its receptor are reduced in diabetic retinas of rats and humans.
- Treating diabetic rats with the GHRH agonist MR-409 (15 µg/kg) preserved retinal structure and ganglion cell survival.
- MR-409 boosted antioxidant pathways (NRF‑2), lowered inflammatory cytokines, reduced VEGF, increased protective PEDF, and decreased vascular permeability.
Practical Outcomes
- For biohackers, this study suggests that GHRH‑activating compounds might have eye‑protective, anti‑inflammatory benefits in the context of diabetes, but the evidence is limited to animal models and a specific dosage. No direct human protocol can be recommended yet; further clinical research is needed before considering sermorelin or similar agents for retinal health.
Summary
In diabetic rats, a drug that mimics the hormone that tells the body to release growth hormone (called a GHRH agonist, specifically MR-409) helped protect the eye's retina from damage caused by high blood sugar. It kept retinal cells alive, reduced inflammation and oxidative stress, and lowered leakiness of blood vessels. The opposite drug (a GHRH blocker) made the eye damage worse.
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.
Study Information
pubmed
2017
2017-11-27T00:00:00.000Z
10.1073/pnas.1718592114
40
50