Posterior capsule opacification
is still an unresolved problem in the tremendously evolving field of refractive lens surgery resulting in secondary visual deterioration and the need of additional interventions.
Our results suggest that the coating of hydrophilic IOLs can be done by bathing an IOL in APC, even if the surface of the IOL is hydrophobic.
In a first approach to identify IOLs that would work well when coated with APC, we tested six different commonly used IOLs for their potential to reduce LEC proliferation (Figure 1). We identified three IOLs that showed promising results and were therefore used for further experiments (Table 1).
The idea of placing an IOL into the capsular bag that carries a pharmaceutical component that would inhibit the formation of PCO is obvious, yet no coated IOLs for this purpose are commercially available.
The sandwich theory that was proposed by Linnola implied a specific role of extracellular matrix (ECM) proteins in the development of PCO [28
]. In this, proteins such as fibronectin are believed to act as a biologic glue to connect the capsule with the IOL [29
]. The firm adhesion of the capsule and the IOL would not allow LECs to migrate into the optical zone and therefore reduce the occurrence of PCO. While fibronectin may therefore be of particular importance to form a barrier with the IOL against LECs, other ECM components such as laminin or collagen IV have also been shown to be expressed in PCO and may act as attractants for LECs. We therefore investigated the influence of laminin and collagen IV in combination with IOLs and APC coated IOLs. Our results show that collagen IV more likely than laminin has a strong effect on the adhesion and proliferation of LECs in a model of LEC proliferation why we chose to use collagen IV for further evaluation in an in vitro
model of PCO (Figure 2).
While in vitro
studies have obvious disadvantages over animal and particularly clinical studies, they allow the investigation of PCO formation and inhibition from different approaches in an almost infinite number. In order to mimic the in vivo
situation better, Gotoh et al. developed an in vitro
model that would allow studying PCO and its inhibition with an IOL without the need to sacrifice animals (Figure 3).
Drawn from our results of the laminin and collagen IV tests, we coated the membrane between the upper and lower chamber with collagen IV. The best result of the tested IOLs were achieved by one hydrophilic (IOL 1) and the hydrophilic IOL with the hydrophobic surface (IOL 3) although the results for all IOLs were very good and differences between all three IOLs were rather small and statistically not significant (Figures 4 and 5). We believe that IOL 1 performed somewhat better because of its slightly bigger size which may have led to a larger contact area on the membrane, leading to more contact of the LECs to the IOL and therefore to APC. Hydrophilic or hydrophobic acrylic materials are flexible and therefore especially appropriate for small incision cataract
surgery. Hydrophobic IOLs have been proposed to perform better in terms of PCO inhibition though [32
]. Hydrophilic IOLs on the other hand are meant to have a better uveal biocompatibility, leading to fewer inflammation and cellular response [35
]. They are also more flexible than hydrophobic IOLs and therefore even better suited for minimal small incision cataract surgery compared to hydrophobic IOLs. As mentioned, these IOLs seem however, to be associated with higher PCO rates [36
], possibly due to the hydrophilic material which is more difficult to handle resulting in less accurate manufacture of the IOL´s sharp edge [38
]. It therefore seems intriguing to develop a hybrid IOL that would have both hydrophilic as well as hydrophobic properties at the same time to overcome this problem.
The results of IOL 1 (hydrophilic) and 3 (hybrid) are very similar and also both IOL total diameters are equal suggesting that the APC coating of the hydrophilic IOL without hydrophobic properties is sufficient to gain results that were not inferior to the hybrid lens with hydrophobic parts. We also did not see major differences in the absolute number of migrated cells underneath the IOLs when compared to each other matching the results that we received by measuring the area of cell distribution but they are significantly lower than for the uncoated IOLs for all tested IOLs (Figure 6). This may seem obvious, but it also shows that the actual amount of cells that migrated underneath the IOLs is significantly lower than in the case of uncoated compared to APC coated IOLs, implying that not only cell spreading is reduced but also cell proliferation and migration, confirming our previous results that were carried out in a cell culture model [19
The amphiphilic character of APC make them particularly well compatible with hydrophilic IOLs as they can get soaked into the water compartment of the IOL as shown before [24
We could assert that not all LECs were completely eradicated by any of the coated IOLs. Particularly in the peripheral parts, were no contact of the IOL to the membrane was achieved, some LECs could be appreciated. It may, however even of an advantage to have some LECs after cataract surgery left, in order to have a better stability of the IOL within the capsular bag. It is also comprehensible, that the contraction of the capsular bag by the remaining LECs and the expression of fibronectin
may provide a higher pressure of the posterior capsule to the edge of the IOL providing better mechanical prevention of LECs growing into the center of the IOL. Thus, a situation in which most LECs in the central part of the IOL are inhibited while most LECs peripherally are not as affected may, considering the sharp edge of the IOL, together with the APC coated surface of the IOL even be beneficial in terms of PCO prevention.
In our first experiments we determined nontoxic concentrations for APC when used with LECs [18
]. We furthermore showed that APC can inhibit proliferation, migration, attachment and spreading of LECs, being the most important cellular features in the formation of PCO development [20
]. In addition to that have we been able to prove that APC inhibit the contraction of LECs by inhibiting the Pi3K/Akt pathway
Further efforts are needed to investigate the performance of APC coated IOLs in an in vivo
situation. We do believe however, that the substantial preliminary work so far make APC a promising candidate as an IOL coating agent for the future.