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，英国每年进行超过 30 万例手术，美国每年进行 200 万例手术。它也是发展中国家视力障碍的主要原因。人工晶状体的最佳植入还可以矫正屈光不正，屈光不正被认为是发展中国家视力障碍的主要原因。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部问题（目前的治疗方法有副作用或缺乏疗效），人工晶状体技术有很大潜力克服这一问题。目前，开发新的人工晶状体设计和材料来取代手术切除的混浊晶状体的光焦度，需要多年的动物工作和临床试验，并且由于成本的原因，进展往往缓慢且渐进。动物模型离人眼不太近，因此许多人体临床试验并没有取得可接受的安全和有效的进展。因此，我们需要的是具有“活”组织的类人眼睛体外模型。 目的：先前的研究已经确定了维持角膜（Zhao 等人，2006，2008）和晶状体（Cleary 等人，2008）的可行性。 ，2010）组织生理稳定至少 10 天。该项目将通过在透明室中真空密封晶状体后部的组织环，将这些结构组合在完整的前眼模型中，以便从后部对解剖结构进行成像。选择猪眼是因为其生物特征与人眼相似（Menduni 等人，2018）。一系列精密电机将模仿需要血液供应来维持其通畅的睫状肌的动作，从而模拟自然的眼睛聚焦。晶状体拉伸器允许在微重力流体环境中拉伸晶状体，从而提供比之前的研究更准确的模型，因为晶状体将保持在生理上真实的温度和水合水平。前房内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来调节（Zhao等，2006）以保持其通畅。第二个泵每 8-20 秒将液体输送到角膜前表面，以模拟泪膜的作用并允许研究干眼状况。环境控制系统将是闭环的，可以控制和连续监测温度、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得到迅速纠正。眼睛模型将是模块化和可扩展的，减少浪费和能源使用，同时转移开发阶段的风险。该系统将能够从 1 个测试单元扩展到 24 个测试单元，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。通过保持光学透明度测量的眼睛模型来评估性能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发生的光学成像和伤口闭合（插入人工晶状体后）。将使用光学和电子显微镜来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，人工晶状体植入的评估和药理学评估将与眼科医生顾问一起进行。