An enhanced model for environmental dry eye: Exploring pathological features and underlying factors

Dry eye is a prevalent ocular surface disease that significantly affects visual acuity and quality of life, with hundreds of millions of people worldwide seeking ophthalmic care due to its impact (Craig et al., 2017). Prolonged visual activities, such as prolonged use of video terminals, near-distance fixed gaze, and driving, have been explicitly identified as important and independent risk factors for dry eye according to the “Consensus of Chinese Dry Eye Experts (2020)" (China Branch of the Asian Dry Eye Association et al., 2020). Prolonged visual activities can lead to dry eye characterized by both increased evaporation factors, belonging to the evaporative type of dry eye, and decreased blink frequency and incomplete blinking factors, associated with the abnormal tear dynamics type of dry eye. Persistent environmental stress induces ocular surface inflammation due to secretion of several chemical mediators from keratocytes, keratoconjunctival epithelial cells, leading to infiltration of immune cells with resulting damage to the corneal nerves(Bron et al., 2017). The pathogenesis of environmental dry eye (EDE) is unique and complex. However, the currently available dry eye models mainly simulate single mechanisms, making it exceedingly rare to find a model that accurately mimics the mechanisms related to prolonged visual fatigue and EDE. Consequently, there is a pressing need to establish an appropriate animal model for studying its underlying mechanisms (see Fig. 1).

Our research team encountered challenges when replicating Nakamura's EDE model using the “desiccated condition with jogging board” approach (Nakamura et al., 2005). This method proved impractical and lacked scalability, impeding the establishment of a reliable experimental setup. When replicating the Simsek C model, rats were immobilized within a stable enclosure. After subjecting them to airflow stimulation, the rats would tend to keep their eyes closed for an extended period to alleviate discomfort caused by the airflow. In contrast, our improved approach leverages the rats' grasping behavior to enhance their body balance. Additionally, rats suspended in this manner experience a sense of insecurity, compelling them to maintain continuous forward fixation of both eyes. This serves to reduce the rats' eye closure time, ensuring that the cornea remains adequately exposed to the airflow environment(Simsek et al., 2018). To overcome these limitations, the team conducted rigorous experimentation and reflection. It is found that the grasping movement of rats helps them maintain body balance, and when in a suspended state, rats experience a sense of insecurity, compelling them to maintain continuous fixation with their eyes facing forward. Based on the aforementioned findings, the research team implemented an innovative modification by transforming the pole into a suspended cylindrical structure made of hollow wire mesh. Furthermore, the team incorporated a frontal blowing air component into the setup. By overcoming the drawbacks of the conventional “desiccated condition with jogging board” dry eye model, this approach successfully establishes the pathogenesis of “prolonged visual fixation."

Preliminary experiments have validated the feasibility and efficacy of the modified model, resulting in the development of a novel EDE model tailored for prolonged visual activities. This model exhibits remarkable simplicity and practicality. It accurately replicates dry eye conditions induced by prolonged visual tasks and demonstrates a high rate of successful model induction. Its user-friendly nature, ease of replication, and potential for widespread application underscore its significance for further comprehensive investigation and validation.

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