Stereolithographic Rapid Prototyping of Clear, Foldable, Non-Refractive Intraocular Lens Designs: A Proof-of-Concept Study.

PURPOSE: A cataract is a cloudy area in the crystalline lens. Cataracts are the leading cause of blindness and the second cause of severe vision impairment worldwide. During cataract surgery, the clouded lens is extracted and replaced with an artificial intraocular lens, which restores the optical power. The fabrication of intraocular lenses using existing molding and lathing techniques is a complex and time-consuming process that limits the development of novel materials and designs. To overcome these limitations, we have developed a stereolithography-based process for producing models of clear lens designs without refractive function, serving as a proof of concept. This process has the potential to contribute toward new lens development, allowing for unlimited design iterations and an expanded range of materials for scientists to explore. METHODS: Lens-like 3D objects without refractive function were fabricated by using stereolithography. A photopolymerizable resin containing 2-phenoxyethyl acrylate, poly (ethylene glycol) dimethacrylate, and a suitable photoinitiator was developed for the production of lens-like 3D object prototypes. The morphology of the printed devices was characterized by scanning electron microscopy. The transparency and thermal properties were analyzed using spectrophotometry and differential scanning calorimetry, respectively. The biocompatibility of the devices was investigated in a cultured human lens cell line (FHL-124), using a standard lactate dehydrogenase assay, and the lenses were folded and implanted in the human capsular bag model. RESULTS: One-piece lens-like 3D objects without refractive function and with loop-haptic design were successfully fabricated using Stereolithography (SLA) technique. The resulting 3D objects were transparent, as determined by UV spectroscopy. The lactate dehydrogenase test demonstrated the tolerance of lens cells to the prototyping material, and apparent foldability and shape recovery was observed during direct injection into a human capsular bag model in vitro. CONCLUSIONS: This proof-of-principle study demonstrated the potential and significance of the rapid prototyping process for research and development of lens-like 3D object prototypes, such as intraocular lenses.

27†Advancing the basic understanding and management of posterior capsule opacification following cataract surgery using human donor eyes.

The human lens is an extraordinary tissue. It has no innervation or blood supply and receives the key building blocks of life from the aqueous and vitreous humours that bathe it. The primary objectives of the lens are to remain transparent and refract light in order to focus light on the retina. These are achieved through exquisite cell organisation and order. However, in time this order can be disrupted and visual quality can deteriorate through the formation of cataract (a clouding of the lens). At present there is no cure for cataract with surgery the only means of resolution. This procedure is performed in ~30 million patients per annum across the globe. Cataract surgery involves making a circular opening (capsulorhexis) in the anterior lens capsule and removal of central lens fibre cells. The product of cataract surgery is known as a capsular bag, which comprises a ring of the anterior capsule and entire posterior capsule. The capsular bag remains in situ, partitions the aqueous and vitreous humours, and in the majority of cases, houses an intraocular lens (IOL). Initial results are superb, but a significant number of patients subsequently develop a condition known as posterior capsule opacification (PCO). This arises from wound-healing responses that lead to fibrosis and partial lens regeneration, which collectively cause light scatter within the visual axis. PCO causes significant visual loss in approximately 20% of patients.While animal systems are commonly employed by investigators to study PCO, the receptor profiles and mechanisms regulating features of PCO can differ between species. Translation of findings from animal studies to human is therefore fraught with difficulties. Human donor tissue provides an outstanding opportunity to investigate the molecular basis of human PCO and explore strategies to better manage the condition. To this end we perform cataract surgery in the laboratory on human donor eyes to generate a capsular bag that can be transferred to a culture dish and maintained in controlled conditions. Often using a match-paired format we have identified a number of factors and pathways that regulate key features of PCO to increase the biological understanding of the problem. In addition, the model has enabled putative pharmacological strategies to be tested and has played a key role in the development and evaluation of IOLs. Collectively, our work on human donor tissue has significantly advanced academic understanding of PCO and facilitated product development that will benefit millions of cataract patients.

Interactions between polyphenolic antioxidants quercetin and naringenin dictate the distinctive redox-related chemical and biological behaviour of their mixtures.

Food synergy concept is suggested to explain observations that isolated antioxidants are less bioactive than real foods containing them. However, mechanisms behind this discrepancy were hardly studied. Here, we demonstrate the profound impact of interactions between two common food flavonoids (individual: aglycones quercetin-Q and naringenin-N- or their glycosides rutin-R and naringin-N+ vs. mixed: QN- and RN+) on their electrochemical properties and redox-related bioactivities. N- and N+ seemed weak antioxidants individually, yet in both chemical and cellular tests (DPPH and CAA, respectively), they increased reducing activity of mixtures synergistically. In-depth measurements (differential pulse voltammetry) pointed to kinetics of oxidation reaction as decisive factor for antioxidant power. In cellular (HT29 cells) tests, the mixtures exhibited properties of a new substance rather than those of components. Pure flavonoids did not influence proliferation; mixtures stimulated cell growth. Individual flavonoids tended to decrease global DNA methylation with growing concentration; this effect was more pronounced for mixtures, but not concentration-dependent. In nutrigenomic studies, expression of gene set affected by QN- differed entirely from common genes modulated by individual components. These results question the current approach of predicting bioactivity of mixtures based on research with isolated antioxidants.

Mutation profiles of congenital cataract genes in 21 northern Chinese families.

Purpose: To identify disease-causing gene mutations in 21 northern Chinese families with congenital cataracts. Methods: Medical record collection and ophthalmologic examinations were conducted for 21 families with congenital cataracts. A volume of 5 ml of peripheral blood was drawn from each participant for genomic DNA isolation. Thirty-four known candidate genes for congenital cataracts were analyzed in the probands of 21 families with targeted next-generation sequencing (NGS). Bioinformatics analysis of the sequence variants was performed through computational predictive programs. Sanger sequencing was used to perform the cosegregation analysis. Genotyping and haplotype analyses were performed in two patients with a p.V44M mutation in the GJA8 gene. Results: Twelve disease-causing mutations were detected in 13 of the 21 patients, and the mutation detection rate was 61.9%. The 12 gene mutations included one nonsense, one splice site, seven missense, and three insert and deletion (INDELs) mutations. Four mutations were novel. Of the 13 patients with pathogenic gene mutations, five (38.5%) were affected by mutations in lens crystallin genes, three (23%) were affected by mutations in connexin genes, three (23%) were affected by mutations in transcription factor genes, one (7.7%) was affected by a mutation in a transmembrane transporter gene, and one (7.7%) was affected by a mutation in a chromatin-modifying protein gene. Two families carried the p.V44M mutation in the GJA8 gene. Haplotype analysis revealed a chromosome region of 475 kb containing the mutation in the GJA8 gene was harbored by two families. Conclusions: Compared with traditional Sanger sequencing, targeted NGS for genetic testing of congenital cataracts markedly increases the mutation detection rate and is cost-effective. The p.V44M mutation in the GJA8 gene was the most common mutation and was due to a founder effect within the Chinese cohort studied. The results of this study expand the gene mutation spectrum of congenital cataracts.