Comparative study of surgical outcomes regarding tear meniscus area and high-order aberrations between two different interventional methods for primary acquired nasolacrimal duct obstruction.

PURPOSE: To compare endonasal dacryocystorhinostomy (EN-DCR) with sheath-guided dacryoendoscopic probing and bicanalicular intubation (SG-BCI) by evaluating tear meniscus area (TMA) and total high-order aberrations (HOAs) for primary acquired nasolacrimal duct obstruction (PANDO). METHOD: We retrospectively reviewed 56 eyes of 42 patients (7 men, 35 women; age, 72.7±13.1 years) who underwent EN-DCR or SG-BCI for PANDO in Toyama University Hospital from February 2020 to June 2022. In the EN-DCR and SG-BCI groups, we measured the patency of the lacrimal passage, preoperative and postoperative TMA, and HOAs of the central 4 mm of the cornea using optical coherence tomography (AS-OCT), six months postoperatively. RESULTS: There was a positive correlation between preoperative TMA and preoperative HOAs in all cases. Postoperative patency of lacrimal passage was 100% in the EN-DCR and 80.8% in the SG-BCI group. There was a significant difference in the number of passages between the two groups (p = 0.01). Preoperative TMA and HOAs showed a significant postoperative decrease in both groups (EN-DCR group: p<0.01, p<0.01, SG-BCI group: p<0.01, p=0.03, respectively). We then calculated the rate of change of preoperative and postoperative TMA and HOAs and compared them between the two groups. The rate of change was significantly higher in the EN-DCR group than that in the SG-BCI group (TMA, p=0.03; HOAs, p=0.02). CONCLUSION: Although both EN-DCR and SG-BCI are effective for PANDO, our results suggest that EN-DCR is more effective in improving TMA and HOAs.

Generation and Characterization of Inhibitory Antibodies Specific to Guinea Pig CXCR1 and CXCR2.

CXCR1 and CXCR2 are chemokine receptors that have different selectivity of chemokine ligands, but the distinct role of each receptor is not clearly understood. This is due to the absence of specific inhibitors in guinea pigs, which are the appropriate species for investigation of CXCR1 and CXCR2 because of their functional similarity to humans. In this study, we generated and evaluated monoclonal antibodies that specifically bound to guinea pig CXCR1 (gpCXCR1) and guinea pig CXCR2 (gpCXCR2) for acquisition of specific inhibitors. To assess the activity of antibodies, we established CHO-K1 cells stably expressing either gpCXCR1 or gpCXCR2 (CHO/gpCXCR1 or CHO/gpCXCR2). CHO/gpCXCR1 showed migration in response to guinea pig interleukin (IL)-8, and CHO/gpCXCR2 showed migration in response to both guinea pig IL-8 and guinea pig growth-regulated oncogene α. The receptor selectivities of the chemokines of guinea pigs were the same as the human orthologs. The inhibitory activities of the anti-gpCXCR1 and anti-gpCXCR2 monoclonal antibodies on cell migration were observed in a concentration-dependent manner. In conclusion, we successfully obtained inhibitory antibodies specific to gpCXCR1 and gpCXCR2. These inhibitory antibodies will be useful to clarify the physiological roles of CXCR1 and CXCR2 in guinea pigs.

Dopamine D1 receptor (DRD1) genetic polymorphism: pleiotropic effects on heritable renal traits.

Because dopamine D(1) receptors (DRD1) influence renal sodium transport and vascular hemodynamics, we examined whether genetic polymorphisms play a role in renal function. We conducted polymorphism discovery across the DRD1 open reading frame and its 5'-UTR and then performed association studies with estimated glomerular filtration rate (eGFR), plasma creatinine (pCr), and fractional excretion of uric acid (FeUA). We used a twin/family group of 428 subjects from 195 families and a replication cohort of 677 patients from the Kaiser health-care organization sampled from the lower percentiles of diastolic blood pressures. Although the coding region lacked common non-synonymous variants, we identified two polymorphisms in the DRD1 5'-UTR (G-94A, A-48G) that occurred with frequencies of 15 and 30%, respectively. In the twin/family study, renal traits were highly heritable, such that DRD1 G-94A significantly associated with eGFR, pCr, and FeUA. Homozygotes for the G-94A minor allele (A/A) exhibited lower eGFR, higher pCr, and lower FeUA. No effects were noted for DRD1 A-48G. Patients in the Kaiser group had similar effects of G-94A on eGFR and pCr. Kidney cells transfected with the -94A variant but not the wild type vectors had increased receptor density. Because the -94A allele is common and may reduce glomerular capillary hydrostatic pressure, G-94A profiling may aid in predicting survival of renal function in patients with progressive renal disease.