Developing eye models to improve eye treatments and contact/intraocular lens technologies

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Cataract surgery is the most common surgery in the developed world with over 300,000 operations in the UK and 2 million operations in the USA each year. It is also a leading cause of visual impairment in the developing world. Optimum implantation of intraocular lenses can also correct refractive error, recognised as the developing world's leading cause of visual impairment. Presbyopia, the loss of eye focus due to a hardening of the crystalline lens, requires reading correction around 45 years of age. This is a universal eye problem in older people (with current treatments associated with side effects or lacking efficacy) which has great potential to be overcome by intraocular lens technology. Currently, the development of new intraocular lens designs and materials to replace the optical power of the surgically removed crystalline lens which has opacified, requires years of animal work and clinical trials and due to the cost, progress tend to be slow and incremental. Animal models are not that close to the human eye, so many human clinical trials do not result in acceptable safe and efficacious advances. Hence, what is required is a human-like eye in-vitro model with 'living' tissue.Aims: Previous research has established the viability of maintaining both corneal (Zhao et al, 2006,2008) and crystalline lens (Cleary et al., 2010) tissue physiologically stable for a period of at least 10 days. This project will combine these structures in a complete anterior eye model by vacuum sealing the ring of tissue posterior to the lens in a transparent chamber to allow imaging of the anatomy from the posterior aspect. A porcine eye has been chosen due to its similar biometry to the human eye (Menduni et al., 2018). A series of precision motors will mimic the action of the ciliary muscle which would need a blood supply to maintain its patency, allowing natural eye focus to be simulated. The lens stretcher allows the lens to be stretched while in the microgravity fluidic environment providing a more accurate model than previous studies as the lens will be maintained at physiologically realistic temperatures and hydration levels. The pressure in the anterior chamber will be monitored by a sensor and adjusted by altering the height differential of the physiological solution (Zhao et al, 2006) passed through the anterior chamber to maintain its patency. A second pump will pass fluid over the anterior surface of the cornea every 8-20 seconds to mimic the action of the tear film and allow dry eye conditions to be investigated. The environmental control system will be closed loop and allow temperature, pressure, oxygen saturation, pH, and flow rates to be controlled and continuously monitored. An alert system linked to the researchers' phones will ensure any deviations can be rapidly rectified. The eye model will be modular and scalable, reducing waste and energy usage while migrating risk in the development phase. The system will be able to scale from 1 to 24 test cells, with the multiple cells controlled by the same system allowing incremental differences to be examined simultaneously or experimental reliability to be tested.Performance will be evaluated by the eye model maintaining optical transparency measured with optical imaging and wound closure occurring (after intraocular lens insertion) assessed by fluorescein dye excited under blue light and observed through a yellow filter. Light and electron microscopy will be used to assess the cell morphology and ultrastructure. Cell viability will be assessed through the LDH and K+ release, ATP depletion, and TBARS levels. Finally evaluation of intraocular lens implantation and pharmacological evaluation will be conducted in conjunction with a consultant ophthalmologist.