Coordinated growth of eye tissues is required to achieve visual acuity. However, visual experience also guides this process. Experimental
myopia can be produced by altering light entering the eye, but also by changing light/dark regimens.
Drug discovery studies demonstrated that γ-
aminobutyric acid (
GABA)-related agonists (e.g.,
baclofen) will mitigate experimental
myopia, and are also drugs studied for their capacity to affect
neurodevelopmental disorders that include
Fragile X Syndrome and related
autism spectrum disorders.
GABA receptors thought to mediate these responses in the eye have been studied in the neural retina as well as the cornea and sclera which are both innervated tissues. In addition to neurons,
lenses express GAD25/65/67
GABA metabolic
enzymes and at least 13
GABA receptor subunits with developmental expression profiles that match neural development. Evidence that lens
GABA receptors are expressed in a cell environment comparable to neurons is seen in the lens expression of
AMPA and
NMDA glutamate receptors together with an unexpectedly comprehensive array of associated signaling
proteins that include post-synaptic-density 95 (PSD95),
calcium calmodulin kinase IIα (CaMKIIα),
Fragile X Syndrome mental retardation protein (FMRP),
ephrin receptors, Ca(V)1.2, 1.3 channels,
cyclin-dependent kinase 5 (Cdk5), and neuronal C-src among others. Moreover, lens cells share fundamental molecular regulatory mechanisms that integrate the regulation and function of these genes at the
DNA,
RNA, and
protein levels in neurons.
GABA has trophic, growth promoting effects early in neuron development and later assumes its classic inhibitory role in the adult neural system. We hypothesize that the extensive parallels between
GABA and
glutamate receptor biology in lens and brain identifies the lens as a site of
GABA agonist drug action affecting experimental
myopia, acting through lens
GABA receptors to similarly affect growth in both elongated cell types.