Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule over the visual axis of the newly implanted intraocular lens (IOL). The developmental pathways underlying PCO are yet to be fully understood and the current literature is contradictory regarding the impact of the recognised risk factors of PCO. The aim of this review is firstly to collate the known biochemical pathways that lead to PCO development, providing an up-to-date chronological overview from surgery to established PCO formation. Secondly, the risk factors of PCO are evaluated, focussing on the impact of IOLs’ properties. Finally, the latest experimental model designs used in PCO research are discussed to demonstrate the ongoing development of clinical PCO models, the efficacy of newly developed IOL technology, and potential therapeutic interventions. This review will contribute to current PCO literature by presenting an updated overview of the known developmental pathways of PCO, an evaluation of the impact of the risk factors underlying its development, and the latest experimental models used to investigate PCO. Furthermore, the review should provide developmental routes for research into the investigation of potential therapeutic interventions and improvements in IOL design in the aid of preventing PCO for new and existing patients.

Cataract surgery removes the diseased lens of the eye replacing it with an intraocular lens, restoring visual acuity. However, accommodation, the lens’ ability to provide dynamic change in focus, is lost. A number of accommodative intraocular lens (AIOL) designs have been considered although none have provided a truly effective clinical AIOL. Two-dimensional titanium carbide (Ti₃C₂T_x) MXene has been used as a transparent conductive electrode within an AIOL feasibility study. Nevertheless, the potential for Ti₃C₂T_xto repress excessive inflammation and promote wound healing following cataract surgery has not been considered. Cataract surgery can trigger chronic inflammation and epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LECs), producing a fibrotic mass across the posterior capsule known as posterior capsule opacification (PCO). With a large surface area and capacity for surface functionalisation, MXene has properties enabling a dual purpose AIOL design with an additional therapeutic role in the repression of pathways leading to PCO development. In this study, Ti₃C₂T_xMXene was investigated to determine its impact on pathways leading to chronic inflammation and EMT using anin vitroLECs model. Ti₃C₂T_xMXene was synthesised and characterised using UV-vis spectroscopy, dynamic light scattering and scanning electron microscopy. Changes in markers linked to inflammation and EMT in Ti₃C₂T_x-treated LECs were measured using enzyme linked immunosorbent assays, quantitative polymerase chain reaction, scratch assay, RNA sequencing for whole-cell gene expression profiling and lipidomics analysis. Ti₃C₂T_xsignificantly reduced the expression of pro-inflammatory cytokines by interleukin 1 beta primed LECs and did not advocate EMT, promoting a positive resolution of the wound healing response. This study supports the role of Ti₃C₂T_xwithin an AIOL design with the potential to repress key developmental pathways leading to PCO.

Advanced glycation end products (AGEs) are protein modifications resulting from the chemical reaction between lysine and arginine residues in proteins, and carbonyl compounds, including glyoxal (GO) and methylglyoxal (MGO). N^ε-carboxymethyllysine (CML) and N^ε-carboxyethyllysine (CEL), formed by glycation from GO and MGO, are among the major AGEs in tissue proteins. Incubation with GO or MGO resulted in higher CML and CEL formation in the two cysteine residues containing αA-crystallin (αAC) than in the cysteine lacking αB-crystallin (αBC). Mass spectrometric data showed K70 and K166 to be heavily modified with CML and CEL in GO- and MGO-modified αAC. In silico analysis of the structure of αAC showed K70 and K166 to be proximal to C142. Mutation or reductive alkylation of cysteine residues in αAC significantly reduced CML and CEL formation. The addition of GSH or N-acetylcysteine enhanced CML and CEL formation in αBC. The introduction of a cysteine residue proximal to a lysine residue in αBC increased the CML and CEL accumulation. Our data showed that CML and CEL formation occurs through a hemithioacetal intermediate formed from the reaction between thiols and GO or MGO. Together, these results highlight a mechanism by which thiols influence protein AGE levels. In addition, CML and CEL are ligands for RAGE, a receptor for AGEs, which has been implicated in several aging and diabetes-associated diseases. Therefore, further understanding of the biosynthesis of CML and CEL could lead to the development of new therapies against those diseases.

A bioactive Ti₃C₂T_x dressing offers a tissue engineering approach to repress inflammation and oxidative stress, improving wound closure rates for chronic wound repair.