Eye Screen

Coordinator:		Prof. Dr. Jochen Graw
Institution:		Institut für Entwicklungsgenetik, Helmholtz Zentrum München
Homepage:		www.helmholtz-muenchen.de/en/idg

Blindness and visual impairment are widespread diseases leading to a significant loss of life quality and shortened lifespan. 50 million people worldwide are blind. Within the German Mouse Clinic we characterise mouse mutants in a standardised phenotyping analysis to establish models for human diseases. In the Eye Screen the optic ability is examined with non invasive methods. Morphological abnormalities of the anterior segments (mainly cornea, iris and lens) are analysed by Scheimpflug Imaging and of posterior segments (mainly retinal fundus, optic disc and vessels) by Optical Coherence Tomography. The primary screening is extended by Laser Interference Biometry to determine different axial eye lengths and vision tests with the Virtual Drum. To complete the eye examinations secondary screening methods such as Electroretinography (a test for retinal function) and histological analysis are performed.
We found ocular irregularities in 13 % of the tested mutant lines. 11 identified eye mutants are affected in a gene that has not been associated with eye development or visual processes before. These include Asxl1, Mysm1, and Prdm5 that code for chromatin modifying proteins. This shows the importance of a regular chromatin structure during eye development. We further indicated Nfya, Pou3f3, and Zscan10 as novel members of the ocular transcription factor group. Moreover, Arvcf, Ftsj1, Jmjd5, and Slc20a2 were identified as novel general eye genes. It became obvious that the rRNA modifying role of Ftsj1 and the hydroxylase activity of Jmjd5 are essential for regular eye growth. Arvcf and Slc20a2 participate in cell-cell communication and phosphate transport, respectively. The underlying mouse models point to a role of these proteins in lens fibre metabolism. Corneal opacities were found in a mouse line that carries a mutation in the receptor gene Ednra encoding a regulator for blood vessel contraction. Interestingly, we confirmed an essential role during eye development also for the cardiovascular genes Fyco1 and Jag1. This further demonstrates a link between eye diseases and cardiovascular risks (Flammer et al., 2013).

                                
Virtual vision test:
In the virtual vision test, the mouse regards a stripe pattern, which moves clockwise or counter clockwise. Seeing mice follow the pattern with a characteristic head movement (head tracking reflex).