GABA_BReceptor Antagonist CGP46381 Inhibits Form-Deprivation Myopia Development in Guinea Pigs

Abstract

The aim was to investigate the effects of the GABAB receptor antagonist, CGP46381, on form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs had monocular visual deprivation induced using a diffuser for 11 days (day 14 to 25). The deprived eyes were treated with daily subconjunctival injections (100 μl) of either 2% CGP46381, 0.2% CGP46381, or saline or received no injection. The fellow eyes were left untreated. Another six animals received no treatment. At the start and end of the treatment period, ocular refractions were measured using retinoscopy and vitreous chamber depth (VCD) and axial length (AL) using A-scan ultrasound. All of the deprived eyes developed relative myopia (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001). The highest dose tested, 2% CGP46381, significantly inhibited myopia development compared to saline (2% CGP46381: −1.08 ± 0.40 D, saline: −4.33 ± 0.67 D, P < 0.01). The majority of these effects were due to less AL (2% CGP46381: 0.03 ± 0.01 mm, saline: 0.13 ± 0.02 mm, P < 0.01) and VCD (2% CGP46381: 0.02 ± 0.01 mm, saline: 0.08 ± 0.01 mm, P < 0.01) elongation. The lower dose tested, 0.2% CGP46381, did not significantly inhibit FDM (P > 0.05). Subconjunctival injections of CGP46381 inhibit FDM development in guinea pigs in a dose-dependent manner.

Alterations of Glutamate and γ-Aminobutyric Acid Expressions in Normal and Myopic Eye Development in Guinea Pigs

“…One hypothesis that emerges from these ideas is that the RGG is closely related to the occurrence and development of myopia. Previous study indicated that the contents of GABA and Glu were upregulated in myopia eyes in chick 53,54 and guinea pigs, 55 and our experimental results obtained the same result. Although in the normal development process the contents of Glu and GABA also were increased, the difference is that the RGG represented the balance between the excitatory and inhibitory neurotransmitters and always keeps an equilibrium state.…”

Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance

“…Specifically, the present findings are in agreement with previous reports of up-regulation of the NSF protein during lens-induced myopia in mouse [ 63 ], and up-regulation of the GABA A receptor mRNA and protein [ 107 ] and increased retinal GABA content during lens-induced myopia in guinea pigs [ 107 , 108 ]. This pattern of expression responses is also consistent with drug studies showing that GABA receptor antagonists inhibit myopia development [ 105 , 109 , 110 ]. Similarly, the GABA C receptor antagonist TPMPA enhanced the protective effect of short periods of normal vision on myopia development in chick, and the GABA A/C agonist Muscimol inhibited the protective effect of normal vision [ 111 ].…”

IMI – Report on Experimental Models of Emmetropization and Myopia

“…Experimental studies have revealed that several GABA receptor antagonists can retard the development of experimental myopia 697,698,705–709. In FDM, antagonists against all three receptor subtypes can retard axial elongation to some extent in chicks and guinea pigs,698,709 while GABA A0r antagonists are effective at preventing the development of LIM in chicks 708.…”