The complex and sensitive anatomy of the human eye not only attracts the attention of ophthalmologists but also scientists who are on the quest for models to study eye diseases. The World Health Organization places an estimate of 2.2 billion people in the world suffering from blindness or a visual impairment, of which nearly 50% are yet to be addressed or even prevented! These eye disorders are impaired vision due to untreated presbyopia (826 million people), untreated refractive error (123.7 million), cataract (65.2 million), glaucoma (6.9 million), corneal opacities (4.2 million), diabetic retinopathy (3 million), and trachoma (2 million).
According to researchers, Patel and team (2013), scientists face challenges in delivery to the eye known as ocular drug delivery. For example, there are many barriers (described as precorneal, dynamic and static) for the drugs to reach. Another challenge is that many drugs do not stay at therapeutic levels in the tissue. This has propelled scientists to develop successful ocular drug delivery systems and models to assess the performance.
One system to assess the effect of molecules being tested for eye diseases is in vivo animal models. They have been used to check the toxicity and irritation if any of potential drug molecules. An example is the Draize test used as the gold standard that involves applying a chemical on an eye of a conscious rabbit with the other eye as the control. Apart from the lack of repeatability and species difference from that of humans the use of animals for such chemical exposures raises ethical issues. According to 2011 published research in the Archives of Toxicology, the Draize eye irritancy tests used more than 20,000 rabbits in the United Kingdom.
Close to 1.37 million animals were used for animal experiments in the United States alone; this figure excludes mice and rats that constitute 90% of animals employed in research. The figures increase with more than 3 million animals (mice, fish, rats and birds-in decreasing order of percentage use) used for experiments in 2011!
These figures raise the question of looking at non-animal models that partially or completely replace the use of live animals in biological and medical experiments. It is encouraging to note that the use of animals has decreased by 40% with a concurrent increase in the use of cell cultures according to Badyal and Desai in The Indian Journal of Pharmacology (2014). This opens up the avenue that research is possible without depending completely on animal systems.
According to scientists, Shafaie and team their article in BioResearch Open Access in 2016 discussed the use of in vitro models that are primary cell cultures from animals and humans. These systems are reproducible, cheaper, easy to handle and provide an understanding of mechanisms of eye diseases and the effects of drugs.
Cornea cultures become important to study the permeation and toxicity of ocular drugs as the cornea is the route of drugs applied topically to the eyes. Examples are rabbit corneal epithelial membrane cultures that have been used to study permeation and transport; human primary corneal epithelial (HCE) cell cultures to assess transport and toxicity.
When drugs are not applied through the cornea, the conjunctiva becomes the route of ocular drug delivery of, especially large and hydrophilic molecules. Primary cultures from rabbits and cows have allowed studying the transport, metabolism and toxicity of molecules.
Given the image processing by the retina, cultures of the RPE or retinal pigment epithelium can offer insights into the biology of these cells. The functions of barriers and tight junctions have been studied using primary rat and bovine RPE cultures.
There is a quote that says, “The eyes are the windows to the soul”. The use of primary cultures of different eye components can aid research to understand and treat these windows avoiding the painful involvement of live animals.
- Patel, A., Cholkar, K., Agrahari, V., & Mitra, A. K. (2013). Ocular drug delivery systems: An overview. World journal of pharmacology, 2(2), 47–64.
- Liebsch M, Grune B, Seiler A, et al. Alternatives to animal testing: current status and future perspectives. Archives of Toxicology 2011;85: 841–858.
- Badyal DK, Desai C. Animal use in pharmacology education and research: the changing scenario. The Indian Journal of Pharmacology2014;46: 257–265.
- Sara Shafaie, Victoria Hutter, Michael T. Cook, Marc B. Brown, and David Y.S. Chau. In VitroCell Models for Ophthalmic Drug Development Applications. BioResearch Open Access 2016 5:1, 94-108.