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，在英国，每年在美国进行300,000多次手术，在美国进行了200万次手术。这也是发展中国家视觉障碍的主要原因。眼内镜头的最佳植入也可以纠正折射误差，这被认为是发展中国家视觉障碍的主要原因。长老会是由于结晶镜的硬化而失明的焦点，需要在45岁左右阅读校正。这是老年人的普遍眼睛问题（当前的治疗与副作用或缺乏功效有关），它具有很大的潜力，可以通过眼内晶状体技术克服。目前，开发新的眼内透镜设计和材料，以取代手术去除的晶体晶状体的光功能，这需要多年的动物工作和临床试验，并且由于成本，进展往往会缓慢且增量。动物模型并不是人类的眼睛，因此许多人类的临床试验并不能带来可接受的安全有效进步。因此，所需的是一种具有“活”组织的人类眼内模型。IAMS：先前的研究确定了维持角膜（Zhao等，2006,2008）和结晶镜（Cleary等，2010）的生存能力，至少在10天。该项目将通过真空将组织环密封到透明腔室中的透镜后的组织环，从而使这些结构结合到完整的前眼模型中，从而允许从后部进行解剖学成像。由于其与人眼类似的生物特征，因此选择了猪眼（Menduni等，2018）。一系列的精密电动机将模仿睫状肌肉的作用，这些睫毛肌需要保持血液供应以保持其通畅，从而可以模拟自然的眼睛焦点。透镜担架允许在微重力液体环境中拉伸镜头，比以前的研究提供了更准确的模型，因为晶状体将保持在生理上现实的温度和水平水平。前腔的压力将通过传感器监测，并通过改变生理溶液的高度差（Zhao等，2006）来调节，以维持其通畅。第二个泵将每8-20秒在角膜的前表面穿过液体，以模仿泪膜的作用，并允许研究干眼症的条件。环境控制系统将是闭环，并允许控制温度，压力，氧饱和度，pH和流速。与研究人员手机相关的警报系统将确保可以迅速纠正任何偏差。眼睛模型将是模块化的，可扩展的，在开发阶段迁移风险的同时，减少了废物和能源的使用。该系统将能够从1到24个测试单元扩展，由相同系统控制的多个单元可以同时检查递增差异或进行测试的实验性可靠性。绩效将通过保持光学成像和伤口闭合的光学透明度来评估（通过插入式插入后，通过光学成像和伤口闭合进行了蓝色的透明透视效果，并通过蓝色的透射率进行了蓝色的透视素，并将其评估。光和电子显微镜将用于评估细胞形态和超微结构。细胞活力将通过LDH和K+释放，ATP耗竭和TBARS水平进行评估。最后，将与顾问眼科医生一起评估人眼透镜植入和药理学评估。