The development of PCO is influenced by patient-related factors, factors related to surgical technique, and the type of intraocular lens (IOL) implanted. Patient-related factors include young age, history of uveitis, glaucoma [6], arterial hypertension, metabolic disease, type of cataract (subcapsular), and injury [7,8,9]. These factors are known to increase the risk of PCO in the immediate postoperative period [9], but the mechanism of action has not been completely clarified. Some authors believe that diabetes may play a role in the promotion of PCO [10] while others have suggested that diabetes is a preventive factor [11]. Moreover, the data on PCO are inconsistent regarding sex distribution. The only IOL-related factors proved to be associated with PCO are a rounded edge and the phacoemulsification technique [12]. The geometry of the optic edge of the IOL is also important, as well as the shape and angulation of the haptics. PCO is much less likely to occur with IOLs that have a sharp posterior optic edge (360°). Mian et al., found that the frequency of posterior capsulotomies performed in patients with three-piece lenses was significantly lower than that in those with one-piece lenses [13]. Furthermore, thorough hydrodissection and aspiration of lens masses and polishing the posterior capsule reduce the occurrence of PCO, but increase the procedure time, which may increase the risk of surgical trauma. Incomplete LEC removal may lead to further proliferation of LECs within traumatized tissues, which exacerbates pro-inflammatory processes [14].

The most common procedure performed to improve visual acuity that provides insight into the fundus of an eye with PCO is laser capsulotomy [15]. This procedure entails making an opening in the posterior capsule on the visual axis. Laser capsulotomy is accepted as a standard and effective treatment for posterior capsule opacification. It is an effective, quick and relatively easy outpatient procedure, but it can produce some complications. Recent studies have not confirmed its association with retinal detachment, however it may be associated with complications, which range from mild short-term increase in intraocular pressure to visual impairment due to cystoid macular edema, or macular holes [16,17]. Trinavarat et al., noticed that laser capsulotomy may lead to IOL damage, subluxation, dislocation, and secondary glaucoma [18]. Moreover, laser capsulotomy is not compatible with the new generation of accommodative lenses, which require the presence of a lens capsule to function [19]. Laser treatment also places a significant financial burden on healthcare systems and is not widely available in developing countries. Therefore, the second course of action is to search for methods to prevent secondary cataracts. Until now, numerous in vitro and experimental animal studies have been conducted, but many have reported undesirable effects on the corneal endothelium [20,21]. Various trials of antiproliferative therapy have been performed in cells cultured in vitro and lens capsule models or in vivo (in rabbits, monkeys, and humans) [22,23,24,25]. Active agents are delivered to LECs via various carriers (including ophthalmic viscoelastic devices, drug delivery systems [DDSs], or slow-release implants) or can be delivered directly to the cell culture medium during in vitro experiments. Various techniques have also been developed for intraoperative application of pharmacological agents to lens cells, including adding them to infusion fluids, using devices that confine them in the capsular space, or coating the IOLs with the test substance [26].

The breakdown of the blood-aqueous humor barrier during cataract surgery causes an immune response. Thereafter, epithelial-mesenchymal transition (EMT) occurs in cells in the lens capsule. The main cause of PCO after cataract surgery is migration and proliferation of LECs. The average number of LECs is approximately 4000–5000/mm², depending on patient age, with a significant decrease in density in those aged 80 years or older. LECs consist of a single layer of cuboidal-cylindrical cells attached to the posterior surface of the anterior lens capsule. A foreign body, such as an IOL, induces an inflammatory reaction, which includes multinuclear leukocytes, giant cells, and fibroblasts, in the anterior chamber in the immediate postoperative period [27,28]. It is worth noting that in animal studies (e.g., in mice from Melinda Duncan’s lab) removal of the lens fiber core also induces the generation of fibrotic cells in the absence of insertion of an IOL. These cells produce cytokines, including transforming growth factor beta (TGF-β), interleukin-1, interleukin-6, basic fibroblast growth factor (bFGF), and tumor necrosis factor alpha (TNF-α), which activate transformation of LECs, proliferation, metaplasia around the equator of the anterior capsule, and migration toward the posterior capsule, leading to thickening and hypertrophy. This process is characterized by fibrosis and contraction reactions due to the activity of actin filaments [29]. Moreover, immunohistochemical studies have identified extracellular matrix (ECM), fibronectin, and collagen molecules on the surface of the IOL [30,31]. Collagen deposition on the IOL and capsule can cause clouding and edema in the posterior lens capsule [31].

The extent to which the IOL becomes coated by LECs depends on the material used in the IOL; its surface [31], optic shape, and diameter; mechanical properties of the haptics [30]; and implantation methods used [32]. The two types of PCOs are caused by two different types of epithelial cells. The first type of PCO involves anterior epithelial cells located in the central zone of the anterior capsule, which consist of LECs that are relatively inactive mitotically. When stimulated, these cells are converted to myofibroblasts, causing fibrous metaplasia. Cells may also migrate toward the posterior capsule, where they proliferate and undergo hypertrophy and hyperplasia on the capsule surface, causing opacification [33]. The second type of PCO occurs when pluripotent cells gather around the equator of the capsule. When activated by interleukins, these cells migrate posteriorly. They do not undergo fibrosis but instead form large, balloon-shaped, or clustered Wedl or bladder cells. They undergo constant mitosis, proliferation, hypertrophy, and hyperplasia, creating clouding [34]. They can also participate in the formation of the fibrous form of PCO through the process of fibrous metaplasia, appearing as fibrous membranes. Metaplasia and inflammatory cells of the iris and ciliary body as well as fibrinous exudate also stimulate development of PCO [35]. Furthermore, the residual cortical fibers may regenerate, creating pathological clouding known as Soemmering’s ring and Elschnig’s pearls and is much more common than fibrotic PCO and is the main cause of a decrease in visual function after cataract surgery [31,32].

In vitro research uses cells derived directly from human or animal lenses. These cells perfectly reflect the processes occurring during formation of PCO because of the original phenotype of the epithelium and their greater sensitivity to external factors. The proliferation and differentiation capacity of cultured LECs can be assessed using microscopy [26]. Alternatively, cells can be obtained by culture of a cell line; these cells are more stable and can provide information about cellular processes but do not completely reflect all processes occurring under actual biological conditions.