Long-Term Change in Renal Function After Intravitreal Anti-VEGF Treatment for Diabetic Macular Edema: A 2-Year Retrospective Cohort Study.

INTRODUCTION: To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). METHODS: A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2 years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. RESULTS: After intravitreal anti-VEGF treatment, eGFR showed a mean decline of -10.4 ± 23.2% and -16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120 mL/min and 15-30 mL/min groups had the greatest decline (-32.0 ± 20.6% and -37.4 ± 30.9%, respectively) while those in the 61-90 mL/min group had the smallest decline (-4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). CONCLUSIONS: In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.

Renal Biomarkers for Treatment Effect of Ranibizumab for Diabetic Macular Edema.

AIMS: To investigate the correlations between renal biomarkers and the treatment outcomes of ranibizumab for diabetic macular edema (DME). METHODS: This hospital-based study retrospectively enrolled 88 eyes from 67 patients who had received one-year intravitreal ranibizumab treatment for DME. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) at baseline and during the follow-up period were recorded. BCVA and OCT characteristics at baseline and their changes after ranibizumab treatment were compared between different proteinuria and estimated glomerular filtration rate (eGFR) groups. RESULTS: Of the 88 eyes studied, those with moderately increased proteinuria had a thicker central subfield foveal thickness (CFT) and a higher proportion of intraretinal cysts than those with no proteinuria (P = 0.012 and 0.045, respectively) at baseline. After one year of ranibizumab treatment, the reduction in CFT was greater in patients with severely increased proteinuria than those with normal to mildly increased proteinuria (P = 0.030). On the other hand, patients with an eGFR <30 tended to have poorer visual improvements than those with normal eGFR (P = 0.044). CONCLUSIONS: After ranibizumab treatment for DME, patients with severe proteinuria tended to gain better anatomical improvement, while those with poor eGFR tended to have poorer visual improvement.

Intestinal FXYD12 and sodium-potassium ATPase: A comparative study on two euryhaline medakas in response to salinity changes.

FXYD proteins are the regulators of sodium-potassium ATPase (Na+/K+-ATPase, NKA). In teleosts, NKA is a primary driving force for the operation of many ion transport systems in the osmoregulatory organs (e.g. intestines). Hence, the purpose of this study was to determine the expression of FXYD proteins and NKA α-subunit in the intestines of two closely related medakas (Oryzias dancena and O. latipes), which came from different salinity habitats and have diverse osmoregulatory capabilities, to illustrate the association between NKA and FXYD proteins of two medaka species in response to salinity changes. The results showed that the fxyd12 mRNA was the most predominant in the intestines of both medakas. The association of FXYD12 and NKA in the intestines of the two medaka species was demonstrated via double immunofluorescent staining and co-immunoprecipitation. Upon salinity challenge, the localization of FXYD12 and NKA was similar in the intestines of the two medaka species. However, the expression profiles of intestinal FXYD12 and NKA (mRNA and protein levels), as well as NKA activity differed between the medakas. These results showed that FXYD12 may play a role in modulating NKA activity in the intestines of the two medakas following salinity changes in the maintenance of internal homeostasis. These findings contributed to knowledge of the expression and potential role of vertebrate FXYD12, the regulators of NKA, upon salinity challenge.

Analysis of experience-regulated transcriptome and imprintome during critical periods of mouse visual system development reveals spatiotemporal dynamics.

Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.