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

白内障手术是发达国家最常见的手术，在英国每年有超过30万例，在美国每年有200万例。它也是发展中国家视力受损的主要原因。人工晶状体的最佳植入还可以矫正屈光不正，这被认为是发展中国家视力受损的主要原因。老花眼是由于晶状体硬化导致的眼睛焦点丧失，需要在45岁左右进行阅读矫正。这是老年人普遍存在的眼病（目前的治疗伴有副作用或缺乏疗效），人工晶状体技术有很大的潜力可以克服这一问题。目前，新的人工晶状体设计和材料的开发，以取代手术取出的混浊晶状体的光学能力，需要多年的动物实验和临床试验，并且由于成本的原因，进展往往是缓慢和渐进的。动物模型并不是那么接近人眼，因此许多人体临床试验并没有产生可接受的安全和有效的进展。因此，需要的是一个具有“活”组织的类人眼睛体外模型。目的：先前的研究已经建立了维持角膜（Zhao et al., 2006,2008）和晶状体（Cleary et al., 2010）组织生理稳定至少10天的可行性。这个项目将把这些结构结合在一个完整的前眼模型中，通过在一个透明的腔室中真空密封晶状体后部的组织环，以便从后侧对解剖结构进行成像。之所以选择猪眼，是因为它的生物特征与人眼相似（Menduni et al., 2018）。一系列精密马达将模拟睫状肌的动作，睫状肌需要血液供应来维持其通畅，从而模拟自然的眼睛聚焦。透镜拉伸器允许透镜在微重力流体环境中拉伸，提供比以前的研究更准确的模型，因为透镜将保持在生理上现实的温度和水合水平。前房的压力将由传感器监测，并通过改变生理溶液通过前房的高度差来调节（Zhao et al ., 2006），以保持其通畅。另一个泵每8-20秒将液体通过角膜前表面，以模拟泪膜的作用，并允许对干眼症进行调查。环境控制系统是闭环的，可以控制温度、压力、氧饱和度、pH值和流量，并对其进行连续监测。与研究人员的手机相连的警报系统将确保任何偏差都能迅速纠正。眼模型将是模块化和可扩展的，减少浪费和能源使用，同时在开发阶段迁移风险。该系统将能够从1到24个测试单元进行扩展，多个单元由同一系统控制，允许同时检查增量差异或测试实验可靠性。性能将通过眼模型来评估，通过光学成像测量保持光学透明度和伤口愈合（人工晶状体植入后），通过蓝光激发荧光素染料评估，并通过黄色滤光片观察。光镜和电镜观察细胞形态和超微结构。通过LDH和K+释放、ATP消耗和TBARS水平来评估细胞活力。最后在眼科顾问医师的协助下进行人工晶状体植入术评估和药理学评估。

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.