Regulation of GABA content by glucose in the chick retina

Abstract

Some visual information is processed in the retina by γ-aminobutyric acid (GABA) signaling. Once retinal degeneration and visual impairment caused by diabetic retinopathy (DR) are affecting an increasing number of people worldwide, and the disease is characterized by hyper- and hypoglycemic events, the authors aimed to investigate how retinal GABA cell content is affected by variations in glucose availability. Using the ex vivo chick retinas exposed to different glucose concentrations, we observed that amacrine cells from both inner nuclear layer (INL) and ganglion cell layer (GCL) as well as their processes in the inner plexiform layer (IPL) released GABA through GABA transporter-1 (GAT-1) after 30 min of glucose deprivation. Extending this insult to 60 min triggered a permanent loss of GABA-positive amacrine cells, caused swelling of IPL and cell death. High glucose (35 mM) for 30 min induced an increment in GABA immunolabeling in both outer and inner retina. Further, glucose deprivation effects could not be reverted by basal glucose levels and high glucose did not prevent GABA loss upon a glucose deprivation insult. Therefore, GABA cell content is differently affected by short-term variations in glucose availability. While high glucose modulates outer and inner GABAergic circuits, glucose deprivation affects mainly the inner retina. Also, consecutive alteration in glucose supply was not able to rescue basal GABA content. Therefore, glucose oscillations interfering with GABAergic retinal functioning during early stages of retinopathies should be further investigated.

Keywords: 1-[2-[[(Diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride; DR; ERG; En; GABA; GABA immunoreactivity; GABA transporter-1; GABA-IR; GAT-1; GCL; INL; IPL; LDH; NNC-711; ONL; OPL; OPs; S; chick retina; diabetic retinopathy; electroretinogram; embryonic day n; ganglion cell layer; glucose deprivation; high glucose; inner nuclear layer; inner plexiform layer; lactate dehydrogenase; oscillatory potentials; outer nuclear layer; outer plexiform layer; sublamina; γ-aminobutyric acid.