Expressions of retinal γ-aminobutyric acid and its receptors in retina of guinea pig eyes after lens induction

Researches showed that gamma aminobutyric acid (GABA),an inhibitory amino acid neurotransmitter,plays a critical role in myopia refractive development.The inhibitory roles of GABA and its receptors antagonists have been confirmed.However,the study on whether GABA participates in the mechanisms of lens-induced myopia (LIM) in guinea pigs is rare.

The aim of this study was to explore the alteration of expression of GABA and its three receptor subtypes in the retinas of guinea pigs with LIM.

Three-week-old healthy guinea pigs were randomized into the normal control group and the model group.The right eyes of the guinea pigs in the normal control group served as the normal control eyes,and the right eyes of the guinea pigs in the model group monocularly fitted with -10 D lens as the experimental eyes,and the fellow eyes of the model group were used as the self-control eyes.The refraction and axial length of eyes were measured by A-sonography and streak retinoscopy before and 4 weeks after modeling.The guinea pigs were sacrificed at the fourth week after modeling,and the retinas were isolated.GABA content in the retinas was assayed by high performance liquid chromatography (HPLC) and the relative expression levels of subtypes of GABA receptors were detected by real-time PCR.All the results were compared among the groups.All experimental protocols and animal handling procedures were approved by the Animal Care and Use Committee of Shandong University of Traditional Chinese Medicine,and were in accordance with the statement of the Association for Research in Vision and Ophthalmology for the use of animals.

At the fourth week after modeling,the mean diopter of the model eyes was (-3.39±0.70)D,which was significantly higher than (1.03±0.68)D of the normal control eyes and (0.77±0.64)D of the self-control eyes in the model group (t=-16.382,-17.113,both at P<0.05).The mean axial length of the experimental eyes was (8.62±0.08)mm,which was increased in comparison with (8.31±0.05)mm of the normal control eyes and (8.32±0.05)mm of the self-control eyes in the model group (t=10.981,15.838,both at P<0.05).The GABA contents were (14.83±1.20),(18.63±1.58) and (15.74±0.96)μmol/g in the normal control eyes,experimental eyes and self-control eyes in the model group,showing significant differences between the experimental eyes and normal control eyes or self-control eyes (t=-6.045,6.876,both at P<0.05).The relative expression levels of GABA_A and GABA_C receptors mRNA in the retinas were significantly increased in the experimental eyes compared with the normal control eyes (t=-3.211,-2.532,both at P<0.05) and the self-control eyes in the model group (t=2.512,5.645,both at P<0.05).However,no significant difference was seen in the relative expression of GABA_B receptors mRNA among the three groups (F=2.676,P>0.05).

The expressions of GABA as well as the mRNA of GABA_A and GABA_C receptor up-regulate, but there is no obvious alteration in the expression of mRNA of GABA_B receptor in the LIM eyes.