Activation of the GABA-alpha receptor by berberine rescues retinal ganglion cells to attenuate experimental diabetic retinopathy

Abstract

PurposeThe aim of this study was to investigate the role and mechanism of berberine (BBR) in the protection of injured retinal ganglion cells (RGCs) in diabetic retinopathy (DR).MethodsExperimental diabetic retinopathy rat model was successfully induced by a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in male SD rats with sufficient food and water for 8 weeks. Animals were randomly divided into four groups: (1) non-diabetic, (2) diabetic, (3) diabetic + BBR + PBS, and (4) diabetic + BBR + SR95531. BBR (100 mg/kg) was given daily by gavage to rats in the group (3) and group (4) for 8 weeks, and weekly intravitreal injections were conducted to rats in the group (3) with 5 μL of 1×PBS and rats in the group (4) with 5 μL of GABA-alpha receptor antagonist SR95531 to investigate the underlying mechanisms. The survival and apoptosis of RGCs were observed by fluorescence gold labeling technology and TUNEL staining. Visual function was evaluated by visual electrophysiological examination. Western blotting and immunofluorescence staining were used to analyze the expression of GABA-alpha receptors in RGCs.ResultsIn an animal model, BBR can increase the survival of RGCs, reduce RGCs apoptosis, and significantly improve the visual function. The reduction of GABA, PKC-α, and Bcl-2 protein expression caused by DR can be considerably increased by BBR. SR95531 inhibits BBR's protective effect on RGC and visual function, as well as its upregulation of PKC-α and Bcl-2.ConclusionBBR is a promising preventive or adjuvant treatment for DR complications, and its key protective effect may involve the regulation of RGC apoptosis through the GABA-alpha receptor/protein kinase C-alpha (GABAAR/PKC-α) pathway.

Exploring the protective effects of herbal monomers against diabetic retinopathy based on the regulation of autophagy and apoptosis: A review

“…[ 110 ] Fang found that Berberine potently defended against RGC apoptosis in the retina of rodent diabetic animals, and its defensive effect might be linked to the GABAARs/protein kinase C-α pathway activation. [ 111 ] In conclusion, traditional Chinese medicine monomer can reduce the optic nerve injury of diabetes retinopathy by regulating apoptosis.…”

Eye Diseases: When the Solution Comes from Plant Alkaloids

“…In fact, diabetic RGCs showed a reduction in the activity and levels of these receptors. It was shown that feeding diabetic rats with berberine increased the levels of GABA receptors, decreasing RGC apoptosis [65]. In addition to RGCs, Müller cells have a prominent role in the pathogenesis of DR. Müller cells are the main glial cells of the retina, and they provide nutritional and regulatory support to the retinal neurons (▶ Fig.…”

Expression of Neurofilaments in the Retina in Experimental Diabetic Retinopathy and the Influence of the Benzodiazepine Receptor Agonist Carbacetam

“…В експерименті була показана наявність ГАМК-рецепторів на амакринових та гангліонарних нейронах сітківки [30]. При цьому при експериментальній ДР показано зниження вивільнення ГАМК та дофаміну у сітківці на тлі значного збільшення вмісту глутамату [14,31]. Посилення імунореактивності глутаматних NMDA-рецепторів спостерігалося в гангліозних, амакринових і біполярних клітинах, а також у внутрішньому і зовнішньому плексиформних шарах сітківки при експериментальному стрептозотоциновому діабеті у щурів [32].…”