We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). The longitudinal changes in retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice treated with FenoNano (n = 6) or the vehicle (n = 6) from ages 8–14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) and the phosphorylation of peroxisome proliferator-activated receptor alpha (PPAR-α) by immunofluorescence. In db/db mice treated with FenoNano, both responses were restored from 8 to 14 weeks of age compared with the diabetic mice treated with the vehicle. At 14 weeks of age, the impaired regulation of retinal blood flow during systemic hyperoxia and flicker stimulation improved to about half of that in the db/db mice treated with FenoNano compared with the db/m control group (n = 5). FenoNano prevented the activation of VEGF and GFAP expression and increased the AQP4 expression and the phosphorylation of PPAR-α detected by immunofluorescence compared with the diabetic mice treated with the vehicle eyedrop. Our results suggested that the fenofibrate nano-eyedrops prevent retinal glial dysfunction via the phosphorylation of PPAR-α and improves the retinal blood flow dysregulation in type 2 diabetic mice.

Prorenin is viewed as an ideal target molecule in the prevention of diabetic retinopathy. However, no drugs are available for inhibiting activation of prorenin. Here, we tested the effect of a prorenin peptide vaccine (V_P) in the retina of a murine model of type 2 diabetes (T2D). To choose the optimal vaccine, we selected three different epitopes of the prorenin prosegment (E1, E2, and E3) and conjugated them to keyhole limpet hemocyanin (KLH). We injected C57BL/6J mice twice with KLH only (as a control vaccine), E1 conjugated with KLH (E1-KLH), E2-KLH, or E3-KLH and compared antibody titers. E2-KLH showed the highest antibody titer and specific immunoreactivity of anti-sera against prorenin, so we used E2-KLH as V_P. Then, we administered injections to the non-diabetic db/m and diabetic db/db mice, as follows: db/m + KLH, db/db + KLH, and db/db + V_P. Retinal blood flow measurement with laser speckle flowgraphy showed that the impaired retinal circulation response to both flicker light and systemic hyperoxia in db/db mice improved with V_P. Furthermore, the prolonged implicit time of b-wave and oscillatory potentials in electroretinography was prevented, and immunohistochemical analysis showed reduced microglial activation, gliosis, and vascular leakage. The enzyme-linked immunosorbent spot assay confirmed vaccinated mice had no auto-immune response against prorenin itself. The present data suggest that vaccination against prorenin is an effective and safe measure against the early pathological changes of diabetic retinopathy in T2D.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P < 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (r = − 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r = − 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

We retrospectively compared the stability of intraocular lenses (IOLs) routinely used at our institution by measuring IOL position after phacovitrectomy for rhegmatogenous retinal detachment (RRD). Patients with RRD who underwent phacovitrectomy with gas tamponade received one of three IOLs: 6-mm, single-piece NS-60YG (NIDEK, 15 eyes); 6-mm, single-piece XY1 (HOYA, 11 eyes); or 7-mm, three-piece X-70 (Santen, 11 eyes). Various parameters associated with the anterior chamber, lens, and IOL were measured by swept-source anterior segment optical coherence tomography (CASIA2; Tomey Corp) before and 1 week and 1 month after surgery. IOL position was determined as follows: IOL position = (postoperative aqueous depth [AQD] − preoperative AQD)/lens thickness. We found no significant difference in axial length between the IOLs (p = 0.97). At 1 week, IOL position was as follows: NS-60YG, 0.32; XY1, 0.24; and X-70, 0.26 (p < 0.05). The respective IOL positions at 1 month were 0.35, 0.27, and 0.28 (p < 0.01). These results indicated the smallest anterior shift with NS-60YG. To replicate the anterior shift of IOL position ex vivo, biomechanical measurement was performed. NS-60YG resisted more displacement force than the other IOLs. Thus, in eyes undergoing phacovitrectomy for RRD, NS-60YG was the most stable of the three IOLs studied.

Purpose: To report results of a modified Yamane technique for scleral fixation of the intraocular lens. Methods: Data from all patients treated with scleral fixation using the Avansee AN6A at our hospital by a single surgeon were obtained and retrospectively analyzed from our database. In our technique, the trailing haptic was externally inserted into the lumen of the 30-G needle. The preoperative measurements included three variables: best-corrected visual acuity (Snellen), intraocular pressure (mmHg), and corneal endothelial cell count (cells/mm ² ). Postoperative measurements included refractive error (D), aqueous depth (mm), tilt (°), decentration (mm), and the three preoperative variables. Results: This study included 20 eyes (mean age, 65.3 ± 13.5 years). Preoperative conditions included lens subluxation (4 eyes), intraocular lens dislocation (13 eyes), and aphakia (3 eyes). The best-corrected visual acuity improved from 20/32 preoperatively to 20/20 postoperatively. The mean preoperative corneal endothelial cell density was 2,282 cells/mm ² and changed to 2,091 cells/mm ² at the last visit. Postoperative refractive error was slightly myopic (−0.13 ± 1.4 D). Regarding the position of fixated intraocular lenses, postoperative tilt was 5.57 ± 3.35° and postoperative decentration was 0.50 ± 0.26 mm. Conclusion: The simplified Yamane technique showed good overall clinical outcomes and stability of refractive predictability when performed by a single surgeon, making it easier to master. Further studies are required to expand on this simplified procedure.