Importance of Metal Biotransformation in Cell Response to Metallic Nanoparticles: A Transcriptomic Meta-analysis Study.

Metallic nanoparticles are increasingly present in our environment, raising concerns on their interactions with living organisms and potential toxicity. Indeed, metallic nanoparticles release metal ions that can be toxic, bioessential, therapeutically active, or combine several of these features. However, human cell responses to different metallic nanoparticles and ions have rarely been compared so far. We propose here a meta-analysis of the transcriptomic responses of human cells to nanoparticles and ions of various metals (titanium, iron, copper, zinc, silver, cadmium, platinum, gold), in order to identify the commonalities and differences between cell responses to these compounds. This analysis revealed that the chemical properties of metals are more important than their known biological functions (i.e., essential metals, toxicity) in governing the cell transcriptome. Particularly, we evidence that the response to nanoparticles is dominated by the response to the ions they contain, and depend on the nanoparticles' solubility. The formulation as nanoparticles impacts the cell response at lower intensity than the released ions, by altering genes related to vesicle intracellular transport and the cytoskeleton. Moreover, we put into light that several metals (i.e., copper, zinc, silver, cadmium, and gold) trigger a common cell response governed by metallothioneins, which coexist with singular signatures that are specific to a given element.

Benefits of Scleral Lens in the Management of Irregular Corneas and Dry Eye Syndrome After Refractive Surgery.

OBJECTIVES: To evaluate the utility of the SPOT scleral lens (Oxygen Permeable Scleral Lens of Thonon; LAO, Thonon-les-Bains, France) in the management of the irregular cornea after refractive surgery. METHOD: We included 19 patients (35 eyes) with irregular corneas after refractive surgery. Patients were fitted with scleral lenses after the failure of conventional contact lenses adaptation. The ophthalmologic examination included measurement of best-corrected visual acuity (BCVA), slitlamp examination, and evaluation of ocular aberrations (Objective Scattering Index [OSI] and higher-order aberration [HOA]). RESULT: Scleral lens fitting increases significantly the BCVA from 0.33 (±0.25) to 0.08 (±0.13) LogMAR (P<0.001). There was also a significant decrease in Ocular Surface Disease Index from 66.2±22.8 to 42.4±18.9 (P<0.001). Ocular aberrations (OAs) are also significantly reduced by the scleral lenses, the mean OSI goes from 7.2 (±4.2) to 3.0 (±1.8) (P<0.001), OA from 2.58 (±1.34) to 1.98 µm (±2.31) (P=0.035), and HOA from 0.94 (±0.51) to 0.48 (±0.23) (P=0.0018). CONCLUSION: Fitting with scleral lenses improves patients' optical and ocular surface problems. Scleral lens restores BCVA and the quality of life. Fitting with scleral lenses is an alternative to further surgery on these fragile eyes and is sometimes the only viable treatment option for the patient.

Correlation between Keratoconus and Pollution.

Introduction: Keratoconus is a corneal ectasia with multifactorial origin. Three risk factors for keratoconus are currently recognized: ultraviolet rays (UV), eye rubbing and atopy. In the current literature, other factors are evoked such as pollution, whose role in the physiopathology of keratoconus is unclear. The effects of particles matter (PM) 2.5 and 10 are the most studied and questioned in the scientific literature.Material and method: A correlation study was carried out to determine the influence of pollution on keratoconus. Fine particulate matter levels were measured according to available WHO data and were correlated with the prevalences of epidemiological studies. These measures were included in the study according to strict selection criteria.Results: The mean pollution rate of the selected studies was 29.1 ± 24.3 µg/m3 for PM2.5 and 57.2 ± 56.2 µg/m3 for PM10. The Pearson test shows a moderate correlation between the prevalence of keratoconus and the levels of PM2.5 (R = 0.51; p = .022) and a strong correlation with the levels of PM10 (R = 0.71; p < .001).Discussion: Fine particulate matter appears to be an emerging risk factor for keratoconus. They are thought to act indirectly by exacerbating known risk factors such as atopy and eye rubbing. And could have a direct action on the cornea by increasing the apoptosis of epithelial cells and interacting directly with the structure of collagen of the stroma.

Incidence of Cystoid Macular Edema After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The incidence of and risk factors for cystoid macular edema (CME) after Descemet membrane endothelial keratoplasty (DMEK) remain uncertain. This study examines the incidence of and risk factors for CME after DMEK. METHODS: This retrospective, single-center study included patients with no history of CME who had undergone DMEK. Patients were examined weekly for 1 month after surgery and at 3 and 6 months after surgery. Follow-up examinations included visual acuity (VA) assessment, pachymetry, anterior segment optical coherence tomography, biomicroscopy, intraocular pressure measurement, and fundoscopy. Eyes suspected of having CME (reduced VA and/or abnormal fundoscopic findings) underwent macular optical coherence tomography. Potential risk factors for CME examined included age, axial length, anterior chamber rebubbling, not using a topical nonsteroidal antiinflammatory after surgery, and concurrent DMEK and cataract surgery (triple-DMEK). RESULTS: Eighty eyes (74 subjects) were included. Eleven eyes (13.8%) developed CME within 6 months after undergoing DMEK. Univariate analyses did not identify any significant CME risk factors. Interestingly, the triple-DMEK procedure did not put subjects at risk for developing CME (P = 0.184). Visual prognosis after medical treatment for CME was excellent, and subjects with and without CME had comparable VA at 6 months [CME: logarithm of the minimum angle of resolution (logMAR) VA = 0.3 (first-third quartile: 0.1-1.0), 20/40; no CME: logMAR VA = 0.3 (0.1-0.5), 20/40; P = 0.391]. CONCLUSIONS: Although CME frequently occurred after DMEK, no CME risk factors were identified. In addition, CME did not significantly affect long-term visual outcomes when it was appropriately treated.

Eye bank prepared versus surgeon cut endothelial graft tissue for Descemet membrane endothelial keratoplasty: An observational study.

The purpose of this article is to examine outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed with cornea bank (CB) prestripped tissue and surgeon stripped tissue (SST).This retrospective study examined subjects who underwent DMEK with CB or surgeon prepared tissue for Fuchs endothelial corneal dystrophy. Best-corrected visual acuity (BCVA), corneal thickness, endothelial cell count (ECC), and complications were examined before and throughout a 6-month postoperative period.Eleven CB and 22 SST subjects were included. Six months after surgery, BCVA was 20/20 or better in 36.4% of CB and 22.7% of SST subjects (P = .43). Median logMAR BCVA was 0.10 (0.00-0.20, 20/25) in group CB and 0.10 (0.10-0.30, 20/25) in group SST. Median preoperative corneal thickness was 614.0 µm (577.5-662.0 µm) and 658.0 µm (606.0-689.0 µm) in CB and SST subjects, respectively (P = .37). Six months after surgery, median corneal thickness was lower in the CB group (571.0 µm [478.0-592.0 µm]), than in the SST group (576.0 µm [531.0-607.0 µm], P = .02). At 6 months, median ECC was 1500.0 cell/mm (1321.5-2049.0 cell/mm, 41% decrease) in group CB and 1403.0 cell/mm (972.5-2010.7 cell/mm, 46% decrease) in group SST (P = .70). Rebubbling was required in 5 CB (45.5%) and 15 SST (68.2%) subjects (P = .39).Fuchs' dystrophy patients have good anatomic and functional DMEK results. Similar outcomes and complication rates occurred with eye bank and surgeon prepared donor tissue.

Validation of an endothelial roll preparation for Descemet Membrane Endothelial Keratoplasty by a cornea bank using "no touch" dissection technique.

Descemet Membrane Endothelial Keratoplasty (DMEK) selectively replaces the damaged posterior part of the cornea. However, the DMEK technique relies on a manually-performed dissection that is time-consuming, requires training and presents a potential risk of endothelial graft damages leading to surgery postponement when performed by surgeons in the operative room. To validate precut corneal tissue preparation for DMEK provided by a cornea bank in order to supply a quality and security precut endothelial tissue. The protocol was a technology transfer from the Netherlands Institute for Innovative Ocular Surgery (NIIOS) to Lyon Cornea Bank, after formation in NIIOS to the DMEK "no touch" dissection technique. The technique has been validated in selected conditions (materials, microscope) and after a learning curve, cornea bank technicians prepared endothelial tissue for DMEK. Endothelial cells densities (ECD) were evaluated before and after preparation, after storage and transport to the surgery room. Microbiological and histological controls have been done. Twenty corneas were manually dissected; 18 without tears. Nineteen endothelial grafts formed a double roll. The ECD loss after cutting was 3.3 % (n = 19). After transportation 7 days later, we found an ECD loss of 25 % (n = 12). Three days after cutting and transportation, we found 2.1 % of ECD loss (n = 7). Histology found an endothelial cells monolayer lying on Descemet membrane. The mean thickness was 12 ± 2.2 µm (n = 4). No microbial contamination was found (n = 19). Endothelial roll stability has been validated at 3 days in our cornea bank. Cornea bank technicians trained can deliver to surgeons an ECD controlled, safety and ready to use endothelial tissue, for DMEK by "no touch" technique, allowing time saving, quality and security for surgeons.

Synthesis and application of lactosylated, 99mTc chelating albumin for measurement of liver function.

Neogalactosylated and neolactosylated albumins are currently used as radiopharmaceutical agents for imaging the liver asialoglycoprotein receptors, which allows the quantification of hepatic liver function in various diseases and also in healthy liver transplant donors. We developed an original process for synthesizing a chelating neolactosylated human albumin using maleimidopropyl-lactose and maleimidopropyl-diethylene triamine pentaacetic acid (DTPA) derivatives. The lactosylated protein (LACTAL) conjugate showed excellent liver uptake compared to nonlactosylated protein and a very high signal-to-noise ratio, based on functional assessment of biodistribution in mice using (99m)Tc-scintigraphy.

Combination of molecular modeling, site-directed mutagenesis, and SAR studies to delineate the binding site of pyridopyrimidine antagonists on the human CCK1 receptor.

A rational combination of site-directed mutagenesis studies, structure-activity relationships, and dynamic-based docking of pyridopyrimidine-derived CCK1R antagonists into a refined three-dimensional model of the CCK1R allowed us to identify the receptor residues and the ligand functional groups implicated in the molecular recognition process. Our results provided unambiguous evidence that the binding site of these antagonists is overlapping that of the C-terminal tetrapeptide of CCK. In particular, Asn333 and Arg336 residues of the CCK1R are essential for high-affinity binding of these ligands. Moreover, the 2-aryl group in the pyridopyrimidine derivatives shares the same binding pocket as the C-terminal Phe side chain of CCK. Our [pyridopyrimidine.CCK1R] complex model is consistent with previous suggestions concerning the molecular basis that governs functional activity and provides useful considerations about the high CCK1 versus CCK2 selectivity of our derivatives and could contribute to fine-tune the rational design of new molecules with optimized properties.