An advanced ex vivo model that preserves the structure and function of the human retina in a controlled laboratory setting was recently revealed. This new approach could have a significant impact on the study of retinal diseases and accelerate the development of targeted therapies.
The retina has been notoriously difficult to study in human subjects, the researchers noted in the study published in Acta Neuropathologica Communications. Access to intact retinal tissue is limited, and commonly used animal models often fail to replicate critical aspects of human retinal anatomy and physiology. Recognizing this gap, researchers have developed a method to maintain the retina’s cytoarchitecture and cellular function in enucleated human and porcine eyes by restoring physiological intraocular pressure (IOP) and fluid dynamics.
The researchers highlighted how these ex vivo models can preserve retinal integrity for up to 24 hours, allowing researchers to observe cellular activity and architecture.
Using a specialized perfusion system, the team infused synthetic aqueous humor through enucleated eyes, mimicking the natural flow and pressure conditions within the eye. This technique not only stabilized the retina’s structure but also minimized cell death and maintained markers of cellular metabolism and astrogliosis—conditions indicative of healthy tissue. In contrast, non-perfused control samples experienced extensive tissue disintegration and cell death within the same time frame.
The experiments were first conducted in porcine eyes—widely used as anatomical surrogates for human eyes—and later replicated in donated human eyes. Both models demonstrated that retinal layers, including ganglion cells and photoreceptors, remained intact and functional.
This innovation could significantly impact the study of retinal diseases involving complex interactions between biomechanical stress and cellular degeneration, the researchers noted.
Additionally, the method could enhance drug development pipelines. Current retinal organoid systems and explant cultures lack key biomechanical elements of living eyes, limiting their ability to predict therapeutic outcomes accurately. By replicating in vivo conditions more closely, the perfused eye model bridges this gap, potentially improving preclinical testing and reducing reliance on animal models.
While promising, the model is not without limitations. The study noted challenges in replicating certain parameters, such as episcleral venous pressure and retinal vascular flow. Extending the preservation timeframe beyond 24 hours is another area for further optimization.