Signalling cascade
and pharmacological intervention of myopia:
The signals from the
retina that arrive in the sclera can be modified pharmacologically. A number of receptor
agonists or antagonists have been identified that suppress experimentally induced (Figure 1B)
refractive errors (mainly cholinergic, dopaminergic, and glucagonergic). Such drugs could
potentially be developed as a therapy against myopia development. Unfortunately, the only
drugs that have made it into phase II clinical trials in children (muscarinic antagonists
pirenzepine and atropine, applied as eye drops or ophthalmic gels), partially lost their effects
when they were applied over extended periods (> 2 years).
Therefore, further research on the signalling cascade from the retina to the sclera is
necessary, and further targets for pharmacological intervention have to be identified:
Project 3/1 Feldkaemper - myopia in transgenic mouse models and drug
screening, Germany
Project 3/2 Reichenbach - Mueller (glial) cells as indicators of
and possible players in myopia, Germany.

Figure 1. (A) schematic illustration of the signalling cascade. Light rays reach the photoreceptor layer (1), the
image is analyzed by the outer retina (2), retinal amacrine cells ('A') carry the information on the sign of defocus
of the retinal image and release growth signals (3) that cross the retinal pigment epithelium (RPE) and the
choroid (4) and reach the sclera. (B) effect of spectacle lenses on refractive development and eye growth in
animal models. Negative lenses move the focus behind the retina, axial eye growth increases and the eye
becomes longer and myopic. Positive lenses focus in front of the retina, eye growth is inhibited and the eye
becomes hyperopic. Below: original data from chicken and monkey, showing development of refractive errors
(left, chicken, Schaeffel laboratory) and compensatory axial eye growth (right, monkey, data courtesy Earl
Smith, Houston).
