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

开发眼部模型以改善眼部治疗和隐形眼镜/人工晶状体技术

• 批准号: 2608661
• 金额: --
• 依托单位: Aston University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2025
• 资助国家: 英国
• 起止时间: 2025 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2608661
• 关键词: Developing; eye; models; improve; treatments

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.

白内障手术是发达国家最常见的手术，每年在英国有超过30万例手术，在美国有200万例手术。它也是发展中国家视力障碍的主要原因。最佳的人工晶状体植入还可以矫正屈光不正，这是发展中国家公认的导致视力障碍的主要原因。老花眼，由于晶状体透镜硬化而导致眼睛焦点丧失，需要在45岁左右进行阅读矫正。这是老年人中普遍存在的眼部问题（目前的治疗与副作用或缺乏疗效相关），其具有通过眼内透镜技术克服的巨大潜力。目前，开发新的眼内透镜设计和材料以替代手术移除的已经混浊的晶状体透镜的光焦度，需要多年的动物工作和临床试验，并且由于成本，进展往往是缓慢和渐进的。动物模型与人眼的距离并不那么近，因此许多人体临床试验并没有带来可接受的安全有效的进展。目的：先前的研究已经建立了维持角膜（Zhao等，2006，2008）和晶状体透镜（Cleary等，2010）组织生理稳定至少10天的时间。本项目将通过真空密封透明腔中透镜后方的组织环，将这些结构联合收割机组合在完整的前眼模型中，以允许从后方对解剖结构进行成像。选择猪眼是因为其与人眼相似的生物统计学（Menduni等人，2018年）。一系列精密电机将模仿睫状肌的动作，这将需要血液供应来保持其通畅，从而模拟自然的眼睛焦点。透镜拉伸器允许在微重力流体环境中拉伸透镜，提供比先前研究更准确的模型，因为透镜将保持在生理上现实的温度和水合水平。前房中的压力将由传感器监测，并通过改变通过前房的生理溶液的高度差（Zhao等人，2006）进行调整，以保持其通畅性。第二个泵将每8-20秒使流体通过角膜的前表面，以模拟泪膜的作用，并允许研究干眼症。环境控制系统将是闭环系统，允许控制和持续监测温度、压力、氧饱和度、pH值和流速。与研究人员手机相连的警报系统将确保任何偏差都能迅速得到纠正。眼睛模型将是模块化和可扩展的，减少浪费和能源使用，同时在开发阶段转移风险。该系统将能够从1个扩展到24个测试单元，由同一系统控制的多个细胞，允许同时检查增量差异或测试实验可靠性。将通过眼模型评价性能，该眼模型保持通过光学成像和伤口闭合测量的光学透明度（眼内透镜插入后）通过在蓝光下激发的荧光素染料评估并通过黄色滤光片观察。将使用光学和电子显微镜评估细胞形态和超微结构。将通过LDH和K+释放、ATP消耗和TBARS水平评估细胞活力。最后，将与眼科顾问医师共同进行眼内透镜植入评价和药理学评价。