Defining initial molecular mechanisms of human cataract formation using light-focusing micro-lenses

Umala Dewi C1, Kabir MDH1, Murphy P1, Ho J2,3 and O'Connor MD1,4

  1. Western Sydney University, Campbelltown, Australia.
  2. Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
  3. St. Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia.
  4. Medical Sciences Research Group, Western Sydney University, Campbelltown, NSW, Australia.

Cataract, caused by opacification of the eye’s lens, affects over 65 million people worldwide. Surgery is the only effective treatment, however, there is great interest in anti-cataract drug development due to: i) the large number of cataract operations performed annually (millions); ii) the cost of these surgeries (billions of dollars); iii) the fact that, despite these surgeries, the number of people affected by cataract is increasing (50.5 million in 1990 to 65.2 million in 2015); and iv) the relatively high incidence of vision-impairing complications that arise from cataract surgery (such as posterior capsule opacification). Environmental risk factors have been associated with cataract formation. The molecular pathologies initiated by different risk factors are likely to be different, yet are poorly understood due to the inability to access human lenses during cataract initialization. To address this, we have established methods for large-scale production of human lens epithelial cells and light-focusing micro-lenses from pluripotent cells. Extensive characterization of these human lens cells and micro-lenses revealed significant functional, morphological and molecular similarities to primary human lenses. An initial study demonstrated the micro-lenses can be used to study clinically-relevant cataract, with assessment of transparency and focusing ability new and quantifiable readouts of cataract formation. Our recent studies suggest other environmental factors can be investigated using human micro-lenses. The micro-lens system also offers an opportunity to re-assess drugs that failed pre-clinical development due to an association with cataract formation in animals.