It is believed that during evolution the eye has been invented independently as many as 40 times (Dawkins, 1996; Land & Nilsson, 2002). Interestingly, however, several types of eyes have been invented during evolution depending on how they work and on the species. These types include the compound eye, found mainly in insects and arthropoda, and the camera type found in different organisms from jellyfish to fish and to mammals. Even these two types can be subdivided depending on the photoreceptor type or optic properties (Land & Nilsson, 2002). More primitive eyes found in invertebrates consist of sensory cells or pigment cells. Perhaps the origin of vision can even be traced back to organisms such as cyonabacteria, which have specialized proteins (opsins) capable of responding to light. The variety of eye structures (especially with regard to the lens) does not end here. Several aquatic eyes have been evolved with four lenses (Bathylychnops exilis), three lenses (in the male copepod Pontella; the female has two) or two lenses (the copepod Sapphirina) (Schwab et al. 2001; Land & Nilsson, 2002). What is fascinating about eye evolution, however, is the conservation of factors that seem to control its formation. One particular gene, pax-6, has been heralded as the eye master gene. Indeed, mutations in pax-6 result in an eyeless phenotype in Drosophila, small eye phenotype in mice and aniridia in humans (Gehring, 2002). Moreover, pax-6 seems single-handedly to initiate the formation of ectopic eyes. For example, when exogenous pax-6 is expressed ectopically in Drosophila, e.g. at the limb imaginal discs, compound eyes with well-differentiated cells types are formed in the limb (Halder et al. 1995). In addition to such effects, expression of pax-6 has been clearly correlated with light-sensing structures throughout the animal kingdom. An interesting case is the cubozoan jellyfish eye. In these animals, a cluster of six different eyes are present in a sensory club, called the rhopalium. Some of the eyes are complex (with lens) whereas others are simple. In addition to these eyes, each rhopalium contains a statocyst, most likely involved in mechanosensing. All of the eyes, including the statocyst, express paxB (an ancestor of pax-6) (Piatigorsky & Kozmic, 2004; Nilsson et al. 2005).
The role of pax-6 in eye development, including the lens, has been studied in detail and a particular network has been delineated. In frogs, upstream of this network is an inhibitor of the bone morphogenetic protein (BMP) pathway and downstream regulators involve pax-6 and six-3 (Zuber et al. 2003). Six-3 is now thought to play a significant role in eye and lens development by regulating pax-6 in a feedback loop. Pax-6 is clearly involved in the differentiation of eye cells during Drosophila eye development as well (Wawersik & Maas, 2000). During vertebrate lens development, which is initiated by interactions of the surface ectoderm and the optic cup, pax-6 and six-3 are expressed in the lens, inducing competent surface ectoderm. Variations of lens development, such as by thickening of the cornea or by differentiation of transparent cells, has been observed in fly larvae as well (Dawkins, 1996; Land & Nilsson, 2002). A direct association of pax-6 and six-3 in lens differentiation has been found because they ectopically induce lens formation when injected exogenously in frog and fish embryos, respectively (Oliver et al. 1996; Altmann et al. 1997).