Hexarelin promotes the survival of retinal ganglion cells after optic nerve transection.
This animal study investigated the neuroprotective effects of hexarelin, a growth hormone secretagogue receptor type 1a (GHS-R1a) agonist, on retinal ganglion cell (RGC) survival following optic nerve transection (ONT) in golden hamsters. Researchers administered hexarelin at varying doses either once or twice daily for five days post-ONT and quantified RGC survival at seven days using Tuj1 immunostaining on retinal whole mounts. Single daily doses (25, 50, and 100 µg/kg) produced a dose-dependent increase in RGC survival compared to saline controls (62.4%, 68.5%, and 74.6% vs. 51.2%, respectively). Twice-daily dosing yielded further improvements, with the highest tested regimen (150 µg/kg twice daily) associated with a survival rate exceeding baseline (109.2% vs. 72.9% for twice-daily saline). The study suggests hexarelin may exert anti-apoptotic neuroprotective effects in the retina, attributed to its GHS-R1a agonism. Key limitations include the use of a single animal species (golden hamster), absence of mechanistic pathway data, and no translation to human subjects or disease models such as glaucoma.
Why this grade: All experiments were conducted exclusively in golden hamsters with no human subjects or clinical data, limiting direct translation to human neuroprotection.
Objective Hexarelin is a growth hormone secretagogue receptor type 1a agonist with a potent anti-apoptotic effect. We studied the neuroprotective effect of hexarelin on the survival of retinal ganglion cells (RGCs) in the retina following optic nerve transection (ONT). Materials and methods Golden hamsters of 8-9 weeks old were used. For 7 days following ONT with one dose of drug, hamsters were injected with single dose of saline, 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin daily for 5 days. For 7 days after ONT with two doses of drugs, saline, 100 μg/kg and 150 μg/kg hexarelin were injected twice daily for 5 days. Survival of RGCs was quantified by immunostaining with Tuj1 antibody in retina whole mount. Results Single daily doses of 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin dose dependently and significantly increased the survival of RGC. The survival rates of RGC in saline, 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin-treated hamsters were 51.2%, 62.4%, 68.5%, and 74.6%, respectively, in 7 days ONT. Two daily doses of saline, 100 μg/kg and 150 μg/kg hexarelin promoted survivals to 72.9%, 91.4%, and 109.2%, respectively, in 7 days ONT. Conclusions Single daily doses of hexarelin dose dependently increased the survival of RGC. Two daily doses of hexarelin increased RGC survival further and 150 μg/kg hexarelin twice daily is optimal for the survival of RGC.
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