The human capsular bag model as a pre‐clinical evaluation tool for IOLs

Abstract

Cataract affects the vision and well‐being of millions. At present the only means of treating cataract is through surgical intervention. Modern cataract surgery typically retains a ring of anterior lens capsule and the entire posterior capsule. This is known as a capsular bag, which can house an intraocular lens (IOL) implant. Initial surgical outcomes are excellent, but with time lens cells that remain following surgery undergo a wound‐healing response. In essence the trauma of surgery provokes cells to proliferate and migrate across the acellular capsular surfaces and in some case the IOL surface. Most importantly, cells ultimately grow within the visual axis, on the central posterior capsule, and undergo fibrotic events that are associated with transdifferentiation to myofibroblasts, matrix deposition and matrix contraction that can lead to a secondary loss of vision termed posterior capsule opacification (PCO). PCO affects a large proportion of patients and is one of the most common fibrotic conditions in the world. It is therefore of great importance to better understand this condition and thus strong experimental systems are required for this purpose. To this end cataract surgery can be performed on human donor eyes within a laboratory setting to provide a biological product that is configured in the same manner as in the patient. This is known as the human capsular bag model. Using this clinically relevant model it has been possible to tease our key regulatory molecules driving human lens growth and fibrosis. While the human capsular bag model has been a useful tool to identify therapeutic targets or test putative therapeutics no pharmacological treatment is currently in clinical use. As a result, the intraocular lens is currently the major tool employed to manage PCO progression. Characteristics required for an IOL include strong optical performance, stability within the lens capsular bag and anti‐PCO properties. To meet international standards for IOL manufacture a number of tests are performed to predict IOL behaviour when implanted. However, ISO guided tests take place in a non‐biological setting and are limited to assessing purely physical characteristics. Therefore, understanding how the IOL interacts with the capsular bag and how wound‐healing responses could influence IOL position and stability is an area of great importance. The human capsular bag model can address this shortfall in the IOL development pipeline to relate design features to IOL stability and anti‐PCO performance in a clinically relevant setting. The presentation will highlight the evolution of the model as a tool for IOL testing and development.