27 Advancing the basic understanding and management of posterior capsule opacification following cataract surgery using human donor eyes

The human lens is an extraordinary tissue. It has no innervation or blood supply and receives the key building blocks of life from the aqueous and vitreous humours that bathe it. The primary objectives of the lens are to remain transparent and refract light in order to focus light on the retina. These are achieved through exquisite cell organisation and order. However, in time this order can be disrupted and visual quality can deteriorate through the formation of cataract (a clouding of the lens). At present there is no cure for cataract with surgery the only means of resolution. This procedure is performed in ~30 million patients per annum across the globe. Cataract surgery involves making a circular opening (capsulorhexis) in the anterior lens capsule and removal of central lens fibre cells. The product of cataract surgery is known as a capsular bag, which comprises a ring of the anterior capsule and entire posterior capsule. The capsular bag remains in situ, partitions the aqueous and vitreous humours, and in the majority of cases, houses an intraocular lens (IOL). Initial results are superb, but a significant number of patients subsequently develop a condition known as posterior capsule opacification (PCO). This arises from wound-healing responses that lead to fibrosis and partial lens regeneration, which collectively cause light scatter within the visual axis. PCO causes significant visual loss in approximately 20% of patients.While animal systems are commonly employed by investigators to study PCO, the receptor profiles and mechanisms regulating features of PCO can differ between species. Translation of findings from animal studies to human is therefore fraught with difficulties. Human donor tissue provides an outstanding opportunity to investigate the molecular basis of human PCO and explore strategies to better manage the condition. To this end we perform cataract surgery in the laboratory on human donor eyes to generate a capsular bag that can be transferred to a culture dish and maintained in controlled conditions. Often using a match-paired format we have identified a number of factors and pathways that regulate key features of PCO to increase the biological understanding of the problem. In addition, the model has enabled putative pharmacological strategies to be tested and has played a key role in the development and evaluation of IOLs. Collectively, our work on human donor tissue has significantly advanced academic understanding of PCO and facilitated product development that will benefit millions of cataract patients.